literature review of hiv/aids pdf

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Stigma in the HIV/AIDS epidemic: A review of the literature and recommendations for the way forward

Anish p. mahajan.

1 UCLA Program in Global Health, University of California, Los Angeles, USA

2 The Robert Wood Johnson Clinical Scholars Program, University of California, Los Angeles, USA

Jennifer N. Sayles

3 Division of General Internal Medicine & Health Service Research, University of California, Los Angeles, USA

Vishal A. Patel

Robert h. remien.

4 HIV Center for Clinical and Behavioral Studies, Columbia University, New York, USA

Daniel Ortiz

5 Charles R. Drew University of Medicine and Science, Los Angeles, USA

Greg Szekeres

Thomas j. coates.

Although stigma is considered a major barrier to effective responses to the HIV/AIDS epidemic, stigma reduction efforts are relegated to the bottom of AIDS program priorities. The complexity of HIV/AIDS related stigma is often cited as a primary reason for the limited response to this pervasive phenomenon. In this paper, we systematically review the scientific literature on HIV/AIDS related stigma to document the current state of research, identify gaps in the available evidence, and highlight promising strategies to address stigma. We focus on the following key challenges: defining, measuring, and reducing HIV/AIDS related stigma as well as assessing the impact of stigma on the effectiveness of HIV prevention and treatment programs. Based on the literature, we conclude by offering a set of recommendations that may represent important next steps in a multifaceted response to stigma in the HIV/AIDS epidemic.

Introduction

HIV/AIDS related stigma (H/A stigma) is invoked as a persistent and pernicious problem in any discussion about effective responses to the epidemic. In addition to devastating the familial, social, and economic lives of individuals, H/A stigma is cited as a major barrier to accessing prevention, care, and treatment services [ 1 – 3 ]. Despite widespread recognition of the differential treatment of persons living with HIV/AIDS (PLHA) by society and its institutions, over the first 25 years of the epidemic, community, national, and global actors have only had limited success in alleviating the deleterious effects of H/A stigma. In describing a sustained response to the HIV/AIDS epidemic, Peter Piot, Executive Director of UNAIDS, identifies tackling stigma and discrimination as one of five key imperatives for success [ 4 ]. At the same time, Piot notes that stigma reduction efforts are relegated to the bottom of AIDS program priorities, often without funding to support such activities [ 4 ].

Much of the rhetoric and literature has cited the complexity of H/A stigma and its diversity in different cultural settings as the primary reasons for the limited response to this pervasive phenomenon [ 5 , 6 ]. The complexity of the phenomenon has led to difficulties and disagreement about how to define H/A stigma and sometimes, to an erroneous conflation of stigma with its related concept of discrimination. The manifestation of H/A stigma not only varies by cultural/national setting, but also by whether one is considering intrapersonal versus societal levels of stigma. The variability in manifestations of stigma by setting and level has led to difficulty in measuring the extent of stigma, assessing the impact of stigma on the effectiveness of HIV prevention/treatment programs, and devising interventions to reduce stigma. These four challenges – defining, measuring, assessing impact of, and reducing stigma – among others have hampered local and global efforts to address H/A stigma.

In this paper, we systematically review the scientific literature on H/A stigma to document the current state of research, with an emphasis on identifying gaps in as well as summarizing existing knowledge on the four aforementioned challenges to effective intervention–defining, measuring, assessing impact of, and reducing stigma. In assessing impact, we critically examine the literature to elucidate the relationship of H/A stigma to the effectiveness of HIV prevention and treatment programs. Finally, based on the available literature, we offer recommendations for each of the four challenges that we believe represent critical next steps in ameliorating the devastating effects of H/A stigma.

Search Strategy & Article Selection

In April 2007, we searched PubMed for all published articles pertaining to HIV/AIDS related stigma. To perform as broad a search as possible, we utilized the search term “HIV AND stigma.” One member of our study team (VAP) reviewed each of the abstracts identified. Data extracted from each abstract included the study’s objective, methodology, and key findings. The geographic region of the study was also recorded. The study team then developed a set of mutually exclusive categories in which to place each of the articles. Categories were created to facilitate summarizing the state of the literature on defining, measuring, assessing impact of, and reducing H/A stigma. To systematically categorize articles, specific criteria were devised for each category. Each article was then placed into one of the categories. In the few instances that an article met criteria for more than one category, the article was placed in the category that more closely resembled the overall objective of the article. Categories and the criteria are as follows:

Theory Based Analyses

Articles mainly explore the theoretical causes and effects of H/A stigma or conceptualize and define H/A stigma.

Psychometric Measurement

Articles mainly focus on the methodology of measuring H/A stigma. The objective of these studies is to create and/or validate a set of items to measure H/A stigma or determine the reliability of such items in various contexts.

Stigma Assessment

Articles assess the various manifestations of H/A stigma among persons living with HIV/AIDS (PLHAs), specific groups such as healthcare workers, or the general population. Articles assessing the consequences of stigma on uptake and effectiveness of HIV prevention and treatment interventions were also included in this category.

Stigma Reduction Interventions

Articles utilize a model to measure H/A stigma, apply a stigma reduction intervention to a specific population, and evaluate the post-intervention burden of H/A stigma.

Legal or Policy Analyses

Articles explore the legal consequences or explore the policy implications of H/A stigma.

Excluded Articles

Articles that did not qualify for any of the above criteria were excluded from the review.

Following the PubMed search, we reviewed bibliographies of major articles for further references not indexed in the search engine. We also reviewed relevant documents from international organizations such as UNAIDS and the World Health Organization. Based on expert suggestions, we also reviewed a subset of relevant articles published after April 2007. Due to the very large number of conference abstracts and the absence of a uniform search engine to identify abstracts related to H/A stigma, we excluded conference abstracts from this review.

Development of Recommendations

After summarizing the state of the literature, we next identified gaps in the available evidence, critical unanswered questions, and promising strategies to address H/A stigma. Based on this, we developed a list of recommendations for responding to the challenges of defining, measuring, assessing impact of, and reducing H/A stigma. We discussed this list of recommendations with a multidisciplinary group of HIV/AIDS professionals including social scientists, clinical researchers, international agency officials, and others at the UCLA Social Justice, Human Rights, and HIV Prevention Think Tank meeting in Sydney, Australia in July 2007. Based in part on our discussion, we further developed and designated 7 of those recommendations as priority next steps to addressing the problem of H/A stigma.

Figure 1 depicts the articles identified in the PubMed search, stratified by category and geographic region. Articles and documents that were not indexed in PubMed, but were identified by other means, are not included in Figure 1 . The literature on H/A stigma is dominated by ‘Stigma Assessment’ studies. Studies in this category generally utilize interview or survey methodology to explore the perceived or enacted stigma experienced by PLHAs, stigmatizing beliefs held by specific groups or the general population, or the effects of stigma on access to and utilization of care, prevention, or treatment services. Fewer articles were found in each of the remaining 4 categories, with surprisingly small numbers of articles focused on developing valid and reliable measures of stigma or on assessing stigma reduction interventions. The dearth of psychometric measurement studies is noteworthy given that a major critique of the available stigma assessment studies is their use of stigma measures that have not been validated. Finally, the majority of articles in each category relate to the North American/European context, revealing a relative paucity of peer-reviewed work on H/A stigma pertaining to generalized HIV epidemics and resource-limited countries.

Flow diagram of articles included in the review.

Defining Stigma: Conceptual Considerations

The conceptualization of H/A stigma that underlies most of the literature today mirrors the stigma concept utilized for a broader set of health and social issues, such as mental illness or unemployment [ 7 , 8 ]. In the H/A stigma literature, the concept of stigma is often not explicitly defined, but rather, is referred to cursorily as “a mark of disgrace” [ 8 ]. The absence of an explicit conceptualization of stigma precludes meaningful appraisal and comparisons of study findings and limits the ability to design effective programs and interventions [ 5 ].

Based on his work in psychiatric hospitals and among criminals and homosexuals, Erving Goffman provided a seminal theorization of health-related stigma in the 1960s [ 9 , 10 ]. Goffman defined stigma as “an attribute that is deeply discrediting,” and that reduces the bearer “from a whole and usual person to a tainted, discounted one” [ 10 ]. He established that society stigmatizes on the basis of what is constitutes as “difference” or “deviance,” and results in a “spoiled identity” [ 5 , 10 ]. The social label of deviance compels stigmatized individuals to view themselves and others to view the stigmatized as discredited or undesirable [ 10 , 11 ].

Socio-cognitive Approach

Goffman’s theorization of stigma was fruitfully adapted and extended by social psychologists interested in how individuals construct categories and link these categories to stereotyped beliefs [ 5 , 8 , 12 ]. This body of work emphasized perceptions of individuals, the origins of stigma in human cognition, and the consequences these individual perceptions have for social interactions [ 5 , 8 ]. When applied to HIV/AIDS, this socio-cognitive framework constrained the concept of H/A stigma to an examination of how PLHAs are labeled and stereotyped by the public, based on their incorrect beliefs and attitudes [ 8 , 15 ], and/or a focus on the specific emotions and cognition of PLHAs. This, in turn, limited the scope of stigma reduction interventions to strategies that might increase the empathy and altruism towards as well as reduce the anxiety and fear of PLHAs among the general population or individual based interventions to assist PLHAs to cope with perceived or experienced stigma. The great majority of articles on H/A stigma measurement and reduction interventions identified in this review either implicitly or explicitly utilizes a socio-cognitive conception of stigma. While important, these approaches exclude a detailed consideration of structural aspects of stigma – the dynamic social/economic/political processes that simultaneously produce and intensify stigma and discrimination [ 8 , 13 , 14 ].

Structural Understanding of Stigma

Recent work in the sociologic and anthropologic disciplines has broadened earlier conceptions of stigma to encompass the structural conditions that contribute to stereotyping [ 5 , 8 ]. One of the key insights is that the process of stereotyping based on an attribute is not only a cognitive phenomenon at the level of the individual but also is determined by a constantly changing social process [ 5 , 8 ]. Parker and Aggelton argue that “it is especially important to think of stigma as a social and cultural phenomenon linked to actions of whole groups of people in the developing world, where bonds and allegiances to families, village, and neighborhood, and community abound” [ 5 ]. Theorizing stigma in this way also highlights the necessity of power – social, economic, or political power – to enable a community to move from individual level perceptions to collectively identify an undesirable difference/attribute, construct stereotypes, and ultimately, to act on the negative stereotype by discriminating against the stigmatized [ 5 , 8 ]. Parker and Aggleton further argue that structural (or social) power is not only needed to enable stigmatization, but also that stigmatization plays key role in producing and reproducing relations of power and control [ 5 , 16 ]. Stigmatization, they argue, is intricately linked with the workings of social inequality by its capacity to cause some groups to be devalued and other groups to feel that they are superior [ 5 ]. In acknowledging that stigma functions at the intersection of culture, power, and difference, Parker and Aggleton argue that stigmatization is central to the constitution of the prevailing social order. Most of the existing research examined in this review does not study H/A stigma within a structural framework that accounts for social processes and social inequality.

Discrimination

By acknowledging the role of social processes and power in the promulgation of stigma, a more precise understanding and definition of discrimination emerges. Discrimination focuses attention on the individual and social producers of stigmatization rather than the recipients of stigma [ 8 ]. Discrimination is a consequence of stigma and defined as “when, in the absence of objective justification, a distinction is made against a person that results in that person being treated unfairly and unjustly on the basis of belonging or being perceived to belong, to a particular group” [ 16 , 17 ]. Stigmatized groups, including PLHAs, are in this way systematically disadvantaged in a variety of ways including in income, education, housing status, medical treatment and health [ 8 ]. Conceptualizing stigma as a combination of individual and social phenomenon underscores the importance of addressing self-imposed, individual, as well as structural (or institutional) discrimination [ 8 ]. Self-imposed discrimination occurs when an individual comes to expect the application of a stereotype to him/herself and out of fear of the expectant rejection and resignation, a priori acts as if discrimination has already been imposed [ 8 , 18 , 19 ]. Individual discrimination refers to more obvious and overt discrimination taking place between two people [ 8 ]. Structural discrimination refers to accumulated institutional practices that work to disadvantage stigmatized groups, and can work in the absence of individual prejudice and discrimination [ 8 ]. Like in other stigmatized medical conditions, most research and intervention for H/A stigma has targeted self-imposed and some aspects of individual discrimination, largely excluding the structural dimensions of discrimination.

Towards a Comprehensive Framework for H/A Stigma

Bruce Link and Jo Phelan offer a broader conceptualization that elucidates both the socio-cognitive and the structural aspects of stigma and the relationship between them [ 8 ]. In their conception, stigma exists when the following four interrelated components converge: 1) individuals distinguish and label human differences, 2) dominant cultural beliefs link labeled persons to undesirable characteristics (or negative stereotypes), 3) labeled persons are placed in distinct categories to accomplish some degree of separation of “us” from “them,” and 4) labeled persons experience status loss and discrimination that lead to unequal outcomes [ 8 ]. Stigmatization is entirely contingent on inequalities in social, economic, and political power that enable the four aforementioned components of stigma to unfold [ 8 ]. Link and Phelan’s conceptualization of stigma may serve as a good starting point for developing a comprehensive framework for H/A stigma, since no such framework was identified in this literature review.

To optimally explain H/A stigma and potential intervention strategies, Link and Phelan’s model may be adapted to reflect the biophysical trajectory of HIV disease [ 11 ] as well as the concept of structural violence [ 16 , 20 ]. Given the several stages of HIV disease from the period of infection onwards – first, a transient flu-like syndrome associated with seroconversion that can last a few weeks, followed by an asymptomatic period of at least a few years, followed by a symptomatic period involving opportunistic infections of varying severity – vulnerability to being stigmatized along the Link and Phelan’s continuum of components varies. For example, a PLHA in the asymptomatic period does not exhibit physical manifestations of HIV disease and is thus more difficult to identify as different by society. Even if he is known to be positive, he may still be less vulnerable to stigmatization since he is stable capable of working and providing for his family, thereby limiting potential separation and status loss despite being labeled. On the other hand, a PLHA who is late in the course of infection and suffering from wasting syndrome is easily identifiable and increasingly vulnerable to discrimination along Link and Phelan’s continuum. In addition to considering the effect of HIV disease stage on H/A stigma, the individual and social context preceding infection should also be understood. Social forces such as poverty, sexism, racism and others create overlapping and reinforcing stigmatized conditions that predispose individuals to HIV infection and limits their ability to access diagnostic and treatment services [ 16 ]. Such forces constitute structural violence and victims of such violence are at increased risk of H/A stigma [ 16 ].

In Figure 2 , we offer a schematic that illustrates a starting point for a conceptual framework for H/A stigma, derived from this review of the literature.

Inequalities in social, political, and economic power are the foundation on which stigmatization is promulgated. For HIV/AIDS related stigma, structural violence and pre-existing stigmas potentiate the power of stigmatizers and enable even more intense stigmatization and discrimination. Stigma exists when labeling, stereotyping, separation/status loss, and discrimination in the setting of power imbalance simultaneously converge. [Ref 5 , 8 , 16 , 17 ].

Measuring Stigma

Valid and reliable measures of H/A stigma are integral to ensuring the rights of PLHA as well as the effectiveness of HIV prevention and treatment programs. Standardized sets of stigma measures, or indicators, can also be developed into scales, which are quantitative instruments that give a numerical result that indicates the severity or extent of H/A stigma measured [ 21 ]. Indicators or scales would enable the tracking of stigma burden over time as well as a comparison of stigma across different regions [ 7 , 22 , 23 ]. Such indicators could determine how stigma is affected by implementation of routine HIV testing and scale up of anti-retroviral therapy. Indicators are needed to evaluate stigma-reduction interventions and assist program managers and donors to identify which anti-stigma approaches are most likely to be successful and how they should be applied in different contexts and among different populations [ 22 ]. Indicators may also be useful to detect if programs or policies are inadvertently exacerbating HIV stigma in the community [ 22 ].

The scope of the indicators needed for fully assessing stigma depends on the overall conceptualization of H/A stigma being utilized. A comprehensive framework requires measurement of stigma across a number of domains and at the individual and structural levels ( Figure 2 ). Indicators are operationalized in the form of questionnaires or derived from thematic analysis of qualitative data such as interviews or focus group discussions [ 21 ]. Questionnaire based indicators are often preferred since they are easier to implement and enable quantification and the development of scales.

Currently Available Indicators

H/A stigma indicators available in the literature to date were generally constructed for research purposes and few have been tested and utilized for surveillance purposes at programmatic or regional levels. These indicators mainly attempt to measure the socio-cognitive aspects of H/A stigma, and most were developed in the U.S. context [ 15 , 24 ]. They are designed to assess stigma from one of two perspectives: the ‘stigmatizers,’ who include the general public or specific groups like healthcare workers, and the ‘stigmatized,’ who include PLHA or high risk groups like commercial sex workers [ 23 ]. For assessing attitudes of stigmatizers, indicators that measure social distancing and support for coercive measures are available. These indicators assess the respondent’s willingness to interact with PLHA in a range of situations, through a set of hypothetical questions about interaction in homes, neighborhoods, and workplaces [ 23 ]. Indicators also query respondents about their support for quarantining PLHA or denying entry of PLHA into the country [ 25 ]. Another set of indicators elicits data on emotional reactions toward PLHA. These indicators are designed to measure the extent to which respondents blame PLHA for their illnesses, consider HIV a retribution from God, and harbor anger, fear, or disgust for PLHA [ 23 , 25 , 26 ]. For assessing perceived or experienced stigma among PLHA, indicators that query how PLHA perceive that their partners, friends, family and community treat PLHA in general and how they would expect them to react if they knew of their HIV status are available [ 23 , 27 – 31 ].

Recent work in Tanzania [ 6 , 22 ] and South Africa [ 32 ] has tested the validity of HIV stigma measures of general population and healthcare provider attitudes toward PLHA. In Tanzania, indicators that captured social distancing consisted of questions about fear of casual contact with PLHA were tested. Utilizing 9 items measuring attitudes toward PLHA, support for coercive measures, and social distancing, Kalichman and colleagues validated an AIDS related stigma scale and demonstrated its reliability among over 2000 respondents in five South African communities [ 32 ].

Gaps In Stigma Measurement

While the aforementioned studies represent important initial steps in developing measures for some aspects H/A stigma, further work is needed to enable accurate and comprehensive assessments. For the categories of existing indicators discussed above, further psychometric refinement of the wording, validation in a diverse range of populations, and standardization of items is needed. As important, however, is developing new sets of indicators to capture the multiple domains of H/A stigma. Indicators measuring social distancing and support for coercive measures do not capture the underlying cause of stigma or the full breadth of experienced discrimination [ 22 , 23 ]. There are few, if any, H/A stigma measures capable of capturing pre-existing and overlapping stigmas of commercial sex work, IV drug use, or homosexuality [ 23 ]. Perhaps most problematic, little research has systematically measured H/A stigma at the structural or institutional levels [ 31 ]. Structural and institutional aspects of stigma are critical drivers of H/A stigmatization and discrimination at all levels, from the individual, household, and social levels to employment and health services access [ 6 , 8 , 16 ]. Taking the institution of healthcare as an example, research on H/A stigma has provided descriptive information about how individual providers think about and serve PLHA but has not revealed how the prevalence and determinants of stigma and discrimination vary by institutional or social context [ 31 ]. Without robust measures of such institutional stigma and the identification of potential levers to affect change, effective stigma reduction interventions cannot be designed.

In the past few years, UNAIDS has been coordinating a concerted effort of international organizations and networks of PLHA to develop a more structurally informed tool to measure stigma experienced by PLHA [ 33 , 34 ]. In addition to creating robust measures of stigma that would enable monitoring programmatic progress over time, ensuring that initiatives are not actually making stigma worse, and comparing regional burdens of stigma, the explicit objectives of the stigma index tool include increasing the understanding of the causes and effects of stigma and increasing the empowerment, involvement, and capacities of PLHA in responding to stigma [ 35 ]. An assessment of stigma reduction activities are now also included among the core indicators of country-level responses to AIDS for the United Nations General Assembly Special Session on HIV/AIDS monitoring program [ 36 ].

Relationship of HIV/AIDS related Stigma to Prevention & Treatment Programs

H/A stigma is considered a barrier to effective HIV prevention and treatment programs. H/A stigma is blamed for low uptake of and poor adherence to prevention and treatment services. Drawing largely on articles from the ‘Stigma Assessment’ category of the review, this section aims to evaluate the evidence for these widely prevalent assertions. We chose to focus our attention on fundamental prevention and treatment challenges, such as reducing HIV risk behavior and maintaining adherence to antiretroviral therapy, respectively, as this approach enabled us to assess the effects of H/A stigma on both general population and PLHA behavior. Additionally, in reference to HIV testing, we looked for evidence that supports the argument that routine provider-initiated HIV testing reduces the deterrent effect of H/A stigma on uptake of testing. Of note, the majority of the literature on H/A stigma and programs identified here utilizes a socio-cognitive conception of H/A stigma.

Stigma & HIV risk behavior

While H/A stigma is widely invoked as a major facilitator of the epidemic, only a few studies have demonstrated an association between stigma and increased risk behavior. Presumed HIV-negative or unknown status individuals in China holding greater stigmatizing attitudes were more likely to be engaged in high risk behavior [ 37 , 38 ]. Among PLHA in South Africa, those who experienced stigma or discrimination were less likely to disclose their HIV status to their sexual partner, and non-disclosure was associated with transmission risk behavior [ 39 ]. Similarly, in a sample of over 2000 sexually active PLHA in France, experiences of H/A discrimination was associated with increased unsafe sex [ 40 ]. To develop prevention programs that effectively reduce risk behavior, more rigorous investigation that better delineates the relationship between stigmatizing attitudes and HIV risk behavior is needed. In particular, the role of social inequalities as well as overlapping stigmas (such as those related to homosexuality or migrancy) in mediating the relationship between H/A stigma and risk behavior must be examined.

Stigma & Biomedical Prevention

Novel biomedical interventions to prevent HIV infection, such as adult male circumcision, pre-exposure prophylaxis, microbicides, and vaccines, represent immense potential to limit the spread of the epidemic. As many of these technologies are still being tested or are in development, little is known about how they will effect and be affected by H/A stigma. HIV vaccine acceptability studies have revealed fear of vaccine induced HIV infection and concerns about being stigmatized based on receiving the vaccine [ 41 – 43 ]. Study participants have also reported that vaccines may be misunderstood by the community as treatment for HIV infection, resulting in being labeled a PLHA and experiencing the attendant stigma [ 42 – 45 ]. Though no empiric data is yet available, the theoretical interplay between H/A stigma and the religious and cultural meaning of circumcision may be a major determinant of the acceptability of adult male circumcision as a prevention intervention. Sawires and colleagues argue that male circumcision offers a new opportunity to engage religious leaders in occupying a central role in advocating for HIV prevention [ 46 ], thereby addressing H/A stigma. Others are more circumspect about the potential benefits of promoting circumcision on H/A stigma, citing the possible contamination of male circumcision by the stigma of female genital mutilation as well as the long history of social power imbalance in the promulgation of circumcision among populations [ 47 ]. As biomedical prevention interventions are rolled out in the future, a detailed understanding of how H/A stigma will affect uptake and use of the interventions is critical to ensure population level effectiveness. Along with this, an over-reliance on biomedical solutions for HIV prevention at the expense of equity, social justice, and human rights mission must be avoided [ 46 ].

Stigma and Prevention of Mother to Child Transmission (PMTCT)

Pregnant women may avoid participating in PMTCT programs due to fear of stigma, discrimination, and violence, particularly from partners when disclosing their HIV status [ 48 , 49 ]. Numerous studies have demonstrated that going against community norms of feeding leads to questions about mother’s HIV status, unwanted disclosure, and fear of stigma from partner, family, and the community [ 50 – 53 ]. Interventions aimed at engaging male partners in PMTCT services, such as sending an invitation home with the partner with a direct request that the man attend the clinic with his partner, have been tried with varying success [ 54 ]. Community level education about specific PMTCT services, targeting pregnant women, community leaders, and people of childbearing age, is critical to improving acceptability of services and diminishing the effects of stigma [ 54 , 55 ].

Stigma, Testing, & Treatment

H/A stigma is documented as a barrier to uptake of HIV testing and treatment services in numerous settings, particularly in resource limited countries [ 1 – 3 , 24 , 56 – 59 ]. In a study of HIV testing and stigma in South Africa, individuals who were not tested for HIV exhibited significantly greater stigmatizing attitudes towards PLHA [ 3 ]. In a study of 112 patients receiving antiretroviral therapy in Botswana two years before the implementation of universal access to treatment, 69% of patients did not disclose their HIV status to their family and a majority of those who reported delaying testing for HIV did so due to fear of H/A stigma [ 60 ].

Without questioning that H/A stigma exists and needs redress, some argue that the profound lack of access to antiretroviral therapy in resource limited countries, rather than stigma, is the real driver of poor uptake of testing and treatment services [ 16 ]. Individuals with advanced HIV/AIDS who exhibit visible signs of disease and are no longer able to work experience severe H/A stigma. Access to therapy triggers a ‘virtuous social cycle’ by treating these individuals and alleviating their visible signs of disease, enabling them to return to a socially and financially productive lives, and sparking interest in testing and treatment among others in the community [ 16 ]. In theory, widespread scale-up of treatment access may turn HIV into a treatable and chronic (rather than deadly) disease, increase uptake of testing, and thereby, ultimately reduce H/A stigma.

The institution of universal access to antiretroviral therapy in Botswana in 2002 provides an opportunity to investigate the effect of scale-up of treatment on testing behavior and stigma. Two years after universal access was in place, enrollment in the treatment program remained far below the targeted projection of eligible patients [ 61 ]. Since low uptake of HIV testing was considered a primary reason for poor enrollment, a routine opt-out HIV testing program was implemented in Botswana in 2004. In opt-out testing, all patients are to be tested as a routine part of medical visits unless they explicitly refused. By increasing the proportion of individuals aware of their status, one of the expected effects of routine opt-out testing is the reduction of H/A stigma [ 61 ], though some have pointed out the potential for increased stigma among women due to problems around disclosure, partner violence, and other gender based stigma [ 62 ]. Eleven months after the introduction of opt-out testing, a cross-sectional study of a probability sample of adults in Botswana was performed to assess attitudes towards routine HIV testing [ 61 ]. Although this study found that 81% of respondents were extremely or very much in favor of routine testing and 60% felt that the policy would reduce stigma, 43% of respondents also believed that routine testing would lead people to avoid going to the doctor for fear of testing and 14% though that the policy could increase gender based violence [ 61 ]. Individuals with stigmatizing attitudes towards PLHA were significantly less likely to have been tested for HIV/AIDS or have heard of routine testing. These data from Botswana underscore the need for further research on the relationship between stigma and routine HIV testing/universal treatment access programs, especially with the 2007 release of the WHO/UNAIDS Guidance for Provider-Initiated Testing and Counseling in Health Facilities [ 63 ].

Even as improving access to antiretroviral treatment in resource limited settings is critical to stemming the HIV epidemic and reducing the underlying social inequities that perpetuate stigma, stigma persists in developed countries which have had near universal access to therapy over the last decade. H/A stigma impedes access to and retention in HIV care [ 64 – 66 ] and adherence to antiretroviral medications [ 67 – 70 ]. Non-disclosure of HIV status for fear of stigma may result in missing doses of medications in order to maintain secrecy about one’s illness [ 70 ]. Studies demonstrating the adverse effects of stigma on retention in care and adherence are emerging in Africa [ 71 , 72 ] and Asia [ 73 ] as well.

Interventions & Social Programs to Reduce HIV/AIDS related Stigma

There are only a small number of published studies on interventions and programs designed to reduce H/A stigma. Given the difficulties in defining and measuring stigma, few such interventions and programs described in the literature have been rigorously evaluated. An overview of stigma reduction strategies for a variety of health conditions summarized the types of approaches that may be employed to address stigma in HIV/AIDS ( Table 1 ) [ 74 ].

Stigma reduction strategies *

The majority of HIV/AIDS specific interventions are designed to reduce stigma at the community level by increasing the tolerance of PLHA among the general population [ 75 ]. The predominant strategy underlying these interventions was education through provision of factual information about HIV/AIDS [ 76 , 77 ]. Most of these were studies of interventions implemented among a small convenience samples of university students in the U.S. without the use of specific stigma measures [ 75 ]. A few studies about interventions aimed at increasing the willingness of healthcare providers to treat PLHAs and at developing coping skills among PHLA were also identified in the literature. These studies were also limited by small sample sizes and the use of ambiguous and untested measures of stigma.

Mass-media campaigns relating to HIV/AIDS knowledge, attitudes and behaviors represent a relatively understudied but widely implemented intervention in resource-limited countries. Such campaigns are broadcast (radio, television, etc) interventions targeting national audiences or small media (posters, pamphlets, dramas, etc) interventions aimed at localities that disseminate messages about HIV/AIDS and could potentially reduce H/A stigma. A systematic review of the effectiveness of H/A mass communication programs revealed only a small positive impact on knowledge of HIV transmission and reduction in risk behavior [ 78 ]. The review, however, was limited by the fact that many of the included studies had weak designs, precluding a definitive conclusion about the impact of the intervention [ 78 ]. Also of note, none of the 24 studies included in the review explicitly evaluated H/A stigma as an outcome. A more recent broadcast intervention specifically designed to address H/A stigma demonstrates that mass media interventions can be effective in reducing stigma. In Botswana, viewers exposed to a 2-year HIV story line in the soap opera, The Bold and the Beautiful , exhibited significantly lower levels of HIV stigma, measured by a validated 5-item stigma scale, compared to non-viewers [ 79 ].

Structural Targets for Social Programs

The majority of existing stigma reduction interventions are based on cognitive-behavioral and social-cognitive models, employing such activities as information dissemination, empathy induction, counseling, and cognitive behavioral therapy [ 5 ]. The focus of these interventions is the individual level. A more comprehensive conceptualization of H/A stigma and discrimination indicates the need to develop stigma reduction programs at the institutional/structural levels. Further, the design of these programs must be informed by the prevailing social and cultural forces that provide dominant groups the power to create stigmatizing and discriminatory conditions [ 5 ]. Parker and Aggelton suggest the need for community level mobilization, with the goal of unleashing the power of resistance on the part of PLHA, in tandem with intervention at the structural level to effectively respond to stigma [ 5 ]. Important structural targets include religious leaders, the judiciary, and the legislative arenas [ 5 , 76 ]. Appropriate reporting and enforcement mechanisms, such as legal aid services and hotlines to report discrimination, are needed along with a socially endorse rights based approach [ 5 ].

Based on principles of community organizing and community building, new models for advocacy and social change in response to HIV/AIDS related stigma should be encouraged [ 5 , 80 ]. The principle of GIPA (Greater Involvement of People Living with HIV/AIDS) is central to effective social program responses to H/A stigma. GIPA aims to realize the rights and responsibilities of PLHA, including the right to self-determination and participation in decision-making processes that affect their lives [ 81 ]. The GIPA Principle, adopted unanimously as part of the Declaration of Commitment on HIV/AIDS, calls for a greater involvement of PLHA at all levels and the creation of supportive political, legal, and social environments [ 81 ]. Public participation of PLHA at community and social levels would not only promote individual level responses to internalized stigma on the part of PLHA, but could also prove a powerful deterrent to stigmatizing impulses of the general population.

H/A stigma is considered a major barrier to effective responses to the HIV epidemic. Yet, there is little consensus among policy-makers and program implementers about how best to define, measure, and diminish the phenomenon. In this systematic review of stigma and the HIV/AIDS epidemic, we examined the existing literature on how H/A stigma is conceptualized, the methodologies for measuring stigma, the available data on the relationship of stigma to the effectiveness of HIV prevention and treatment programs, and interventions and programs for reducing stigma. Link and Phelan’s [ 8 ] theory that stigma is the convergence of labeling, stereotyping, separation, and discrimination by a stigmatizers with access to social, political, and/or economic power offers a good starting point for conceptualizing H/A stigma, particularly when the potentiating effects of structural violence [ 16 ] and pre-existing stigmas are accounted for. Though valid measures of stigma that capture perceived and enacted stigma among PLHA as well as stigmatizing attitudes of healthcare workers and the general population are increasingly available, widespread use of the measures in research and program implementation has not yet occurred. Also, few measures of structural or institutional measures of H/A stigma have been developed or rigorously tested. The literature on HIV prevention and treatment programs indicates that stigma does indeed limit uptake of such critical services as PMTCT, testing, and antiretroviral therapy, even as access to such programs has improved with scale-up. Finally, few specific interventions and social programs to reduce H/A stigma have been rigorously evaluated. Perhaps more problematic, most interventions are individual focus, aiming to increase the knowledge and empathy of potential stigmatizers or improving the ability of PLHA to cope with stigma and discrimination. Few social programs that address stigma promulgated by structural and institutional factors were found in the peer reviewed literature.

Prior to describing our recommendations, we highlight two important limitations of this analysis. In this paper, we systematically reviewed the life sciences and biomedical literature, the primary repository of peer-reviewed academic articles on H/A stigma. Although we supplemented the literature from PubMed with references found in the articles as well as relevant grey literature including reports from international organizations, other relevant sources, particularly relating to sociological, policy, and legal analyses, may not have been captured. Similar systematic searches in search engines such as Socio-file and Westlaw should be conducted. A second and related limitation concerns the restricted assessment of discrimination in this review. Due to the already broad scope of the review, discrimination was only examined as it directly relates to stigma. Broader aspects of discrimination pertaining to legal systems and human rights initiatives and their effects on stigma were not explored in depth.

Recommendations For the Way Forward

Based on the literature review and discussion with a multidisciplinary set of HIV/AIDS experts at the 2007 UCLA Social Justice, Human Rights, and HIV Prevention Think Tank, we developed the following recommendations for addressing stigma in the HIV/AIDS epidemic. Due to the multifaceted nature of H/A stigma, these recommendations are intended for the broad array of individuals, communities, and institutions involved in responding to the HIV/AIDS epidemic, including PLHA, researchers, program implementers, and civil society/government leaders. These recommendations are in no way meant to be exhaustive, but rather, represent what we feel are critical next steps for responding to H/A stigma given the current state of the epidemic.

Defining H/A Stigma

Develop a comprehensive conceptual framework for H/A stigma that incorporates both the socio-cognitive and the structural aspects of stigma as well as captures the effects of pre-existing and overlapping stigma related to poverty, race, gender, sexual orientation, etc.

Recent work in the fields of sociology and anthropology has persuasively demonstrated that the process of stigmatization relies as much on socio-cultural processes and power as on the cognitive processes of labeling and stereotyping at the individual level. Conceptualization of H/A stigma to date, however, is mostly based on a socio-cognitive approach. A more complete understanding how H/A stigma manifests and operates in a multifaceted way is integral to developing effective strategies to measure, assess the impact of, and reduce H/A stigma.

Measuring H/A Stigma

Whenever applicable, encourage the use of valid and reliable stigma measures by research projects and program implementers.

Although stigma is considered one of the greatest challenges to addressing the HIV epidemic, data that accurately describes and quantifies stigma is often not available to program implementers and policy-makers. This type of data is not only important for determining the efficacy of specific stigma reduction interventions, but also crucial to understanding the effect stigma may have on the success of prevention and treatment programs. Consistent and widespread surveillance of stigma utilizing valid measures would also enable program implementers to identify and assist specific at-risk and HIV-positive subgroups who may be experiencing heightened perceived or enacted stigma when accessing prevention and treatment programs.

Support the development of a standardized set of measures for the structural/institutional domains of H/A stigma

Although social and cultural forces in the family, neighborhood, or workplace often play an integral role in systematically discriminating against PLHAs, research on developing measures of stigma has mostly focused on individuals and their potentially stigmatizing attitudes. Policy-makers and funders should support research that aims to develop valid measures of structural and institutional H/A stigma. In addition to enabling a more comprehensive assessment of stigma over time, such measures would help identify and evaluate potential levers to reduce stigma at the structural/institutional level.

Assessing Impact of H/A Stigma on Programs

The following recommendations emerge from stigma related concerns associated with provider-initiated opt-out HIV testing: 1) promote a supportive social and legal framework to minimize unintended consequences of provider initiated opt-out HIV testing, 2) implement stigma reduction interventions among healthcare providers, and 3) support further research on the relationship between stigma and routine HIV testing.

Though H/A stigma is a barrier to accessing the entire spectrum of HIV prevention and treatment services, perhaps the most urgent research questions from a programmatic perspective relate to how the stigma of HIV testing can be overcome, particularly in generalized epidemics where fewer than 15% of the population has ever been tested [ 63 ]. HIV testing is the primary gateway to both prevention and treatment services. While provider initiated opt-out testing as recommended by the W.H.O. and UNAIDS is likely to increase the numbers of people tested [ 63 ], data from Botswana indicates that some people may avoid going to the doctor out of fear of testing and women who are tested may be subject to intimate partner violence [ 61 ], suggesting that prevailing stigma in the general population leads to unintended but significant consequences. Policy-makers and civil society should encourage community preparedness and social mobilization as well as engage relevant legal and public service organizations to minimize these unintended consequences. Provider-initiated programs also underscore the problem of stigmatizing attitudes of healthcare providers [ 64 , 82 – 84 ] and the potential for coercion of patients to test. As provider initiated testing is rolled out, program implementers should institute specific stigma reduction interventions for healthcare providers and ensure consistent monitoring and evaluation of the opt-out testing process. Finally, further research on how stigma effects and is affected by provider initiated testing programs is needed both in real time and in the long run to identify potential adjustments to enhance uptake of testing and novel social consequences of the program.

Promote and document the ‘virtuous social cycle’ that access to antiretroviral therapy provides for stigmatized individuals by 1) linking the rollout of treatment programs with community level stigma reduction interventions and 2) measuring stigma longitudinally as universal access and utilization is achieved.

By treating visible signs of disease and enabling PLHA to return to socially and economically productive lives, antiretroviral therapy can trigger a ‘virtuous social cycle’ [ 16 , 85 ]. However, access to therapy alone is often not sufficient to ensure improvement in the lived experiences of PLHA, due to persistent social stigma as well as the attendant challenges of adhering to pill-taking and following up at provider appointments in the setting of limited social support. Policy-makers and program implementers should link treatment programs with specific interventions to empower PLHA to cope with disclosure of HIV status to a trusted family member or friend as well as maintain or re-integrate into family and community life while on therapy. Rollout of antiretroviral therapy should also be accompanied with specific social marketing and mass media campaigns to address stigmatizing attitudes and stereotypes in the general population.

Reducing H/A Stigma

Promote reform of laws and policies that enable stigma and discrimination of men who have sex with men (MSM), injecting drug users (IDUs), commercial sex workers (CSWs), and migrants.

Current law and policy in many countries directly contribute to and/or exacerbate pre-existing stigma and discrimination associated with at-risk groups. Pre-existing stigma not only predisposes these vulnerable individuals to greater H/A stigma and discrimination, but also critically reinforces stereotyping and status loss of all afflicted with HIV/AIDS, regardless of how they may have acquired the infection. Funders and civil society should support advocacy groups that promote the repeal of laws and policies that criminalize consensual homosexual activity, prohibit syringe possession and needle exchange [ 86 ], facilitate violent policing of CSWs [ 87 ], and require proof of residency status to access services. On the other hand, where protective legislation on HIV/AIDS discrimination is in place, support for enforcement and targeted information campaigns for stakeholders about rights afforded by such legislation should be provided. The work of the Lawyer’s Collective HIV/AIDS Unit [ 88 ], an Indian non-governmental organization engaged in a variety of legal and policy activities to secure and protect the rights of PLHA as well as groups vulnerable to HIV infection, is a good example of the kind of sustained advocacy needed at the structural level while stigmatizing attitudes and norms about HIV/AIDS at the individual level are addressed.

Develop and implement community-based interventions that are designed to mobilize PLHA and the range of other sympathetic social actors (opinion leaders, clergy, etc) to address maladaptive self-stigmatizing behaviors and to advocate against discrimination in the wider community.

Approaches to reducing stigma must be multifaceted and multilevel. Multifaceted to account for the range of stigmatizing conditions that track with HIV/AIDS stigma. Multilevel to account for individual and structural levels of stigma and discrimination. Parker and Aggleton persuasively argue that stigma and stigmatization function at the intersection between culture, power, and difference, and thus, are central to establishing the prevailing social order [ 5 ]. Thus, interventions based on community organizing and building among PLHA as well as potentially sympathetic social and community entities, that aim to ‘unleash the power of resistance on the part of the stigmatized,’ are important avenues for the root causes of H/A stigma and discrimination [ 5 , 80 , 89 ].

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Systematic Reviews

The Centers for Disease Control and Prevention (CDC) conducts systematic reviews using a comprehensive search of literature on HIV prevention, care, and treatment topics. The systematic review approach is an evidence-based way to synthesize the literature and expand our knowledge of factors related to HIV transmission and prevention. The team uses systematic review techniques to synthesize data descriptively or through quantitative methods, such as meta-analysis, using statistical techniques. Qualitative methods can also be used.

Search PRS Publications

Crepaz, N., Salabarria-Pena, Y. Mullins, M. M., Gunn, J., & Higa, D.H. (2023). Systematic review of social determinants of health associated with HIV testing among Hispanic/Latino men who have sex with men (MSM) in the United States . AIDS Education and Prevention, 35 (1), 36–53. doi: 10.1521/aeap.2023.35.1.36

Kamitani, E., Wichser, M. E., Mizuno, Y., DeLuca, J. B., & Higa, D. H. (2023). What factors are associated with willingness to use HIV pre-exposure prophylaxis (PrEP) among U.S. men who have sex with men not on PrEP? A systematic review and meta-analysis. Journal of the Association of Nurses in AIDS Care, 34 (2), 135-145. doi: 10.1097/JNC.0000000000000384

Becasen, J. S., Morris, J. D., Denard, C. L., Mullins, M. M, Kota, K. K. & Higa, D. H. (2022). HIV care outcomes among transgender persons with HIV infection in the United States, 2006–2021 . AIDS , 36(2), 305–315 doi: 10.1097/QAD.0000000000003109

Barker, E. K., Malekinejad, M., Merai, R., Lyles, C. M., Sipe, T. A., DeLuca, J. B., Ridpath, A. D., Gift, T. L., Tailor, A., & Kahn, J. G. (2022). Risk of human immunodeficiency virus acquisition among high-risk heterosexuals with nonviral sexually transmitted infections: A systematic review and meta-analysis . Sexually Transmitted Diseases, 49 (6), 383-397. https://doi: 10.1097/OLQ.0000000000001601

Gunn, J. K. L., Rooks-Peck, C., Wichser, M. E., Denard, C., McCree, D. H., Jeffries, W. L., 4th, DeLuca, J. B., Ross, L. W., Herron, A., Barham, T., Flores, S. A., & Higa, D. H. (2022). Effectiveness of HIV stigma interventions for men who have sex with men (MSM) with and without HIV in the United States: A systematic review and meta-analyses. AIDS and Behavior, 26(Suppl 1), 51–89. https://doi.org/10.1007/s10461-021-03358-x

Higa, D. H., Crepaz, N., Mullins, M. M., Adegbite-Johnson, A., Gunn, J. K. L., Denard, C., Mizuno, Y., & the Prevention Research Synthesis Project. (2022). Strategies to improve HIV care outcomes for people with HIV who are out of care . AIDS, 36 (6), 853-862. https://doi: 10.1097/QAD.0000000000003172

Mizuno, Y., Gelaude, D. J., Crepaz, N., Kamitani, E., DeLuca, J. B., Leighton, C. A., Wichser, M. E., & Smith, D. K. (2022). Health care providers’ views on clinic infrastructure and practice models that may facilitate HIV preexposure prophylaxis (PrEP) prescribing: A qualitative meta-synthesis . Health Promotion Practice, 23 (6), 999–1014. https://doi.org/10.1177/15248399211038364

Roland, K. B., Higa, D. H., Leighton, C. A., Mizuno, Y., DeLuca, J. B., & Koenig, L. J. (2022).  HIV patient navigation in the United States: A qualitative meta-synthesis of navigators’ experiences .  Health Promotion Practice, 23(1), 74-85. doi: 10.1177/1524839920982603

Crepaz, N., Mullins, M. M., Higa, D., Gunn, J. K. L., & Salabarría-Peña, Y. (2021). A rapid review of disparities in HIV prevention and care outcomes among Hispanic/Latino men who have sex with men in the United States. AIDS Education and Prevention , 33(4), 276-289. doi: 10.1521/aeap.2021.33.4.276

Jeffries, W. L., IV, Flores, S. A., Rooks-Peck, C. R., Gelaude, D. J., Belcher, L., Ricks, P. M., & Millett, G. A. (2021).  Experienced homophobia and HIV infection risk among U.S. gay, bisexual, and other men who have sex with men: A meta-analysis external icon .  LGBT Health, 8 (1), 1-10. doi: 10.1089/lgbt.2020.0274

Malekinejad, M., Barker, E. K., Merai, R., Lyles, C. M., Bernstein, K.T., Sipe, T. A., DeLuca, J. B., Ridpath, A., Gift, T. L., Tailor, A., & Kahn, J. G. (2021). Risk of HIV acquisition among men who have sex with men infected with bacterial sexually transmitted infections: A systematic review and meta-analysis . Sexually Transmitted Diseases . 48(10), e138-e148. doi: 10.1097/OLQ.0000000000001403

Higa, D. H., Crepaz, N., McDonald, C. M., Adegbite-Johnson, A., DeLuca, J. B., Kamitani, E., Sipe, T., & Prevention Research Synthesis (PRS) Project (2020).  HIV prevention research on men who have sex with men: A scoping review of systematic reviews, 1988–2017 external icon .  AIDS Education and Prevention, 32 (1), S1-7. doi: 10.1521/aeap.2020.32.1.1

Johnson, W., Rivadeneira, N., Adegbite-Johnson, A., Neumann, M. S., Mullins, M. M., Rooks-Peck, C., Wichser, M., McDonald, C., Higa, D., & Sipe, T. (2020).  Human immunodeficiency virus prevention for people who use drugs: Overview of reviews and the ICOS of PICOS external icon .  Journal of Infectious Disease, 222 (Suppl. 5), S278–300. doi: 10.1093/infdis/jiaa008

Kamitani, E., Johnson, W. D., Wichser, M. E., Adegbite, A. H., Mullins, M. M., & Sipe, T. A. (2020).  Growth in proportions and disparities of HIV PrEP use among key populations identified in national goals: Systematic review & meta-analysis of published surveys external icon . JAIDS Journal of Acquired Immune Deficiency Syndromes, 84 (4), 379-386. doi: 10.1097/QAI.0000000000002345

Roland, K. B., Higa, D. H., Leighton, C. A., Mizuno, Y., DeLuca, J. B., & Koenig, L. J. (2020). Client Perspectives and Experiences With HIV Patient Navigation in the United States: A Qualitative Meta-Synthesis .  Health Promotion Practice, 21 (1), 25-36. doi: 10.1177/1524839919875727

Becasen, J. S., Denard, C., Mullins, M. M., Higa, D., & Sipe, T. A. (2019). Estimating the prevalence of HIV and sexual behaviors among the U.S. transgender population: A systematic review and meta-analysis, 2006 – 2017.  American Journal of Public Health , 109(1):e1-e8. doi: 10.2105/AJPH.2018.304727

Bradley, E., Forsberg, K., Betts, J. E., DeLuca, J. B., Kamitani, E., Porter, S. E., Sipe, T. A., & Hoover, K. W. (2019).  Factors affecting pre-exposure prophylaxis implementation for women in the United States: a systematic review external icon .  Journal of Women’s Health, 28 (9), 1272-1285. doi.org/10.1089/jwh.2018.7353

Collins, C. B. Jr., Baack, B. N., Tomlinson, H., Lyles, C., Cleveland, J. C., Purcell, D. W., Ortiz-Ricard, A., & Mermin, J. (2019).  Selecting evidence -based HIV prevention behavioral interventions for HIV-negative persons for national dissemination external icon .  AIDS and Behavior, 23 (9), 2226-2237. doi.org/10.1007/s10461-019-02433-8

Kamitani, E., Mizuno, Y., Wichser, M., Adegbite, A. H., DeLuca, J. B., & Higa, D. H. (2019). Mapping the study characteristics and topics of HIV pre-exposure prophylaxis research literature: A scoping review external icon .  AIDS Education and Prevention, 31 (6), 505–522. doi: 10.1521/aeap.2019.31.6.505

Mizuno, Y., Higa, D., Leighton, C., Mullins, M., & Crepaz, N. (2019).  Is co-location of services with HIV care associated with improved HIV care continuum outcomes?  A systematic review external icon .  AIDS Care, 31 (11), 1323-1331. doi: 10.1080/09540121.2019.1576847

Painter, T., Song, E. Y., Mullins, M. M., Mann-Jackson, L., Alonzo, J., Roboussin, B. A., & Rhodes, S. D. (2019).  Social support and other factors associated with HIV testing by Hispanic/Latino gay, bisexual, and other men who have sex with men in the U.S. south external icon .  AIDS and Behavior, 23 (Suppl. 3), 251-265. doi: 10.1007/s10461-019-02540-6

Rooks-Peck, C. R., Wichser, M. E., Adegbite, A. H., DeLuca, J. B., Barham, T., Ross, L., Higa, D., Sipe, T. A., & the Prevention Research Synthesis Project. (2019).  Analysis of systematic reviews of medication adherence interventions for persons with HIV, 1996-2017 external icon .  AIDS Patient Care and STDs, 33 (12), 528-537. doi: 10.1089/apc.2019.0125

DiNenno, E. A., Prejean, J., Delaney, K. P., Bowles, K., Martin, T., Tailor, A., Dumitru, G., Mullins, M. M., Hutchinson, A., & Lansky, A. (2018).  Evaluating the evidence for more frequent than annual HIV screening of gay, bisexual, and other men who have sex with men in the United States: Results from a systematic review and CDC expert consultation external icon .  Public Health Reports, 133 (1), 3-21. doi:10.1177/0033354917738769

Henny, K. D., Wilkes, A. L., McDonald, C. M., Denson, D. J., & Neumann, M. S. (2018).  A rapid review of eHealth interventions addressing the continuum of HIV care (2007-2017) external icon .  AIDS and Behavior, 22 (1), 43-63. doi:10.1007/s10461-017-1923-2

Kamitani, E., Wichser, M. E., Adegbite, A. H., Mullins, M. M., Johnson, W. D., Crouch, P. C., & Sipe, T. A. (2018).  Increasing prevalence of self-reported HIV pre-exposure prophylaxis (PrEP) use in published surveys: A systematic review and meta-analysis external icon .  AIDS, 32 (17), 2633-2635. doi: 10.1097/QAD.0000000000001983

Mizuno, Y., Higa, D. H., Leighton, C. A., Roland, K. B., DeLuca, J. B., & Koenig L. J. (2018). Is HIV patient navigation associated with HIV care continuum outcomes? AIDS, 32 (17), 2557-2571. doi:10.1097/QAD.0000000000001987

Rooks-Peck, C. R., Adegbite, A. H., Wichser, M., Ramshaw, R., Mullins, M., Higa, D., Sipe, T. A., & the Prevention Research Synthesis Team. (2018). Mental health and retention in HIV care: A systematic review and meta-analysis. Health Psychology , 37(6), 574-585. doi:10.1037/hea0000606

DiNenno, E. A., Prejean, J., Irwin, K., Delaney, K. P., Bowles, K., Martin, T., Tailor, A., Dumitru, G., Mullins, M. M, Hutchinson, A. B., & Lansky, A. (2017).  Recommendations for HIV screening of gay, bisexual, and other men who have sex with men – United States, 2017 external icon .  MMWR Morbidity and Mortality Weekly Report, 66 (31), 830-832. doi: 10.15585/mmwr.mm6631a3

Kamitani, E., Sipe, T. A., Higa, D. H., Mullins, M. M., Soares, J., & the CDC HIV/AIDS Prevention Research Synthesis (PRS) Project. (2017).  Evaluating the effectiveness of physical exercise interventions in persons living with HIV: Overview of systematic reviews external icon .  AIDS Education and Prevention, 29 (4), 347-363. doi: 10.1521/aeap.2017.29.4.347

Purcell, D. W., Higa D., Mizuno, Y., & Lyles, C. (2017).  Quantifying the harm and benefits from serosorting among HIV-negative gay and bisexual men: A systematic review and meta-analysis external icon .  AIDS and Behavior, 21 (10), 2835-2843. doi: 10.1007/s10461-017-1800-z

Sipe, T. A., Barham, T. L., Johnson, W. D., Joseph, H., Tungol-Ashmon, M. L., & O’Leary, A. (2017). Structural interventions in HIV prevention: A taxonomy and descriptive systematic review. AIDS and Behavior, 21 (12):3366-3430. doi: 10.1007/s10461-017-1965-5

Higa, D. H., Crepaz, N., Mullins, M. M., & the Prevention Research Synthesis Project. (2016).  Identifying best practices for increasing linkage to, retention, and re-engagement in HIV medical care: Findings from a systematic review, 1996-2014 external icon .  AIDS and Behavior, 20 (5), 951-966. doi: 10.1007/s10461-015-1204-x

Abad, N., Baack, B. N., O’Leary, A., Mizuno, Y., Herbst, J. H., & Lyles, C. M. (2015).  A systematic review of HIV and STI behavioral interventions for female sex workers in the United States external icon .  AIDS and Behavior, 19 (9), 1701-1719. doi: 10.1007/s10461-015-1013-2

Crepaz, N., Tungol-Ashmon, M. V., Vosburgh, H. W., Baack, B. N., & Mullins, M. M. (2015).  Are couple-based interventions more effective than interventions delivered to individuals in promoting HIV protective behaviors? A meta-analysis external icon .  AIDS Care, 27 (11), 1361-1366. doi: 10.1080/09540121.2015.1112353

Crepaz, N., Baack, B. N., Higa, D. H., & Mullins, M. M. (2015).  Effects of integrated interventions for reducing HIV transmission risk and improving care continuum outcomes among persons living with HIV in the United States: A systematic review and meta-analysis, 1996-2014 external icon .  AIDS, 29 (18), 2371-2383. doi: 10.1097/QAD.0000000000000879

Charania, M. R., Marshall, K. J., Lyles, C. M., Crepaz, N., Kay, L. S., Koenig, L. J., Paul J Weidle, P. J., Purcell, D. W. & the HIV/AIDS Prevention Research Synthesis (PRS) Team. (2014).  Identification of evidence-based interventions for promoting HIV medication adherence: Findings from a systematic review of U.S.-based studies, 1996-2011 external icon .  AIDS and Behavior, 18 (4), 646-660. doi: 10.1007/s10461-013-0594-x

Crepaz, N., Tungol-Ashmon, M. V., Higa, D. H., Vosburgh, H. W., Mullins, M. M., Barham, T., Adegbite, A., DeLuca, J., Sipe, T. A., White, C. M., Baack, B. N., & Lyles, C. M. (2014).  A systematic review of interventions for reducing HIV risk behaviors among people living with HIV in the United States, 1988–2012 external icon .  AIDS, 28 (5), 633–656. doi: 10.1097/QAD.0000000000000108

Lansky, A., Finlayson, T., Johnson, C., Holtzman, D., Wejnert, C., Mitsch, A., Gust, D., Chen, D., Mizuno, Y., & Crepaz, N. (2014).  Estimating the number of persons who inject drugs in the United States by meta-analysis to calculate national rates of HIV and hepatitis C virus infections external icon .  PLoS ONE, 9 (5), e97596. doi: 10.1371/journal.pone.0097596

Higa, D. H., Crepaz, N., Marshall, K., Kay, L., Vosburgh, H. W., Spikes, P., Lyles, C. M., & Purcell, D. W. (2013).  A systematic review to identify challenges of demonstrating efficacy of HIV behavioral interventions for gay, bisexual, and other men who have sex with men (MSM) external icon .  AIDS and Behavior, 17 (4), 1231-1244. doi: 10.1007/s10461-013-0418-z

Liau, A., Crepaz, N., Lyles, C. M., Higa, D. H., Mullins, M. M., DeLuca, J. B., Petters, S., Marks, G. & the HIV/AIDS Prevention Research Synthesis (PRS) Team. (2013).  Interventions to promote linkage to and utilization of HIV medical care among HIV-diagnosed persons: A qualitative systematic review, 1996-2011 external icon .  AIDS and Behavior, 17 (6), 1941-1962. doi: 10.1007/s10461-013-0435-y

Chin, H. B., Sipe, T. A., Elder, R. W., Mercer, S. L., Chattopadhyay, S. K., Jacob, V., Wethington, H. R., Kirby, D., Elliston, D. B., Griffith, M., Chuke, S. O., Briss, S. C., Ericksen, I., Galbraith, J. S., Herbst, J. H., Johnson, R. L., Kraft, J. M., Noar, S. M., Romero, L. M., Santelli, J., & Community Preventive Services Task Force (2012).  The effectiveness of group-based comprehensive risk-reduction and abstinence education interventions to prevent or reduce the risk of adolescent pregnancy, Human Immunodeficiency Virus, and sexually transmitted infections: two systematic reviews for the Guide to Community Preventive Services external icon .  American Journal of Preventive Medicine, 42 (3), 272-94. doi: 10.1016/j.amepre.2011.11.006

Collins, C. B., Jr., Edwards, A. E., Jones, P. L., Kay, L., Cox, P. J., & Puddy, R. W. (2012).  A comparison of the Interactive Systems Framework (ISF) for dissemination and implementation and the CDC Division of HIV/AIDS Prevention’s Research-to-Practice model for behavioral intervention external icon .  American Journal of Community Psychology, 50 (3-4), 518-529. doi: 10.1007/s10464-012-9525-7

Henny, K. D., Crepaz, N., Lyles, C. M., Marshall, K. J., Aupont, L. W., Jacobs, E. D., Liau, A., Rama, S., Kay, L. S., Willis, L. A., & Charania, M. R. (2012).  Efficacy of HIV/STI behavioral interventions for heterosexual African American men in the United States: A meta-analysis external icon .  AIDS and Behavior, 16 (5), 1092-1114. doi: 10.1007/s10461-011-0100-2

Higa, D. H., Marks, G., Crepaz, N., Liau, A., & Lyles, C. M. (2012).  Interventions to improve retention in HIV primary care: A systematic review of U.S. studies external icon .  Current HIV/AIDS Reports, 9 (4), 313-325. doi: 10.1007/s11904-012-0136-6

Purcell, D. W., Johnson, C. H., Lansky, A., Prejean, J., Stein, R., Denning, P., Gau, Z., Weinstock, H., Su, J., & Crepaz, N. (2012).  Estimating the population size of men who have sex with men in the United States to obtain HIV and syphilis rates external icon .  Open AIDS Journal, 6 (Suppl. 1), 98-107. doi: 10.2174/1874613601206010098

Vosburgh, H. W., Mansergh, G., Sullivan, P. S., & Purcell, D. W. (2012).  A review of the literature on event-level substance use and sexual risk behavior among men who have sex with men external icon .  AIDS and Behavior, 16 (6), 1394-1410. doi: 10.1007/s10461-011-0131-8

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Marshall, K., Crepaz, N., & O’Leary, A. (2010). A systematic review of evidence-based behavioral interventions for African American youth at risk for HIV/STI infection, 1988–2007. In D. McCree, K. T. Jones, & A. O’Leary (Eds.),  African Americans and HIV/AIDS: Understanding and addressing the epidemic  (pp. 181-209). New York, NY: Springer. doi: 10.1007/978-0-387-78321-5_9

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Health-Related Quality of Life in People with Advanced HIV Disease, from 1996 to 2021: Systematic Review and Meta-analysis

• Substantive Review
• Open access
• Published: 14 May 2024

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• I. Portilla-Tamarit   ORCID: orcid.org/0000-0002-2187-8731 1 , 2 , 3 , 4 ,
• M. Rubio-Aparicio   ORCID: orcid.org/0000-0002-2599-4246 2 , 5 ,
• M. J. Fuster-RuizdeApodaca   ORCID: orcid.org/0000-0003-4304-7194 6 , 7 ,
• J. Portilla-Tamarit   ORCID: orcid.org/0000-0003-0881-9646 2 , 3 , 4 ,
• S. Reus   ORCID: orcid.org/0000-0002-3320-9754 2 , 3 , 4 , 8 &
• J. Portilla   ORCID: orcid.org/0000-0002-3676-9511 2 , 3 , 4 , 8  

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The purpose of the study was to assess the effects of advanced HIV disease (AHD) on health-related quality of life (HRQoL) in PLHIV, the changes in HRQoL outcomes over the last 25 years, and the differences between countries according to level of economic development. We conducted a systematic review and meta-analysis. The search was conducted in PubMed and Web of Science using the terms: “health-related quality of life”, “HQRoL”, “HIV”, “AIDS”, “advanced HIV disease” and “low CD4 cells”. Studies inclusion criteria were: adult population; initiated after 1996 and published before July 2021; clinical trials, cross-sectional, cohort, and case–control studies; studies analyzing the relationship between AHD and HRQoL; English or Spanish language. Standardized mean differences ( d +) were calculated to estimate the effect size for the meta-analyses. Summary statistics were calculated using a random-effects model, and analyses of effect moderators, using mixed-effects models. The meta-analysis included 38 studies. The results indicated that HRQoL is worse in patients with AHD compared to those without. The main HRQoL domains affected were overall health perception and concern and physical and functional health and symptoms. We found a moderate impact for age and gender on some HRQoL domains. There were no differences in relation to socioeconomic inequities, country of residence, or time period analyzed. In conclusion, advanced HIV disease has a negative impact on health and well-being in PLHIV. Our results show that despite all the advances in antiretroviral treatments over the last 25 years, AHD persists as a source of extreme vulnerability, regardless of where PLHIV live.

El objetivo del estudio fue evaluar los efectos de la enfermedad avanzada de sida (EAS) en la calidad de vida relacionada con la salud (CVRS) en personas que viven con el VIH (PVVIH), los cambios experimentados en la CVRS en los últimos 25 años y las diferencias entre países. Realizamos una revisión sistemática y metaanálisis. La búsqueda se llevó a cabo en PubMed y Web of Science utilizando los términos: “calidad de vida relacionada con la salud”, “CVRS”, “VIH”, “SIDA”, “enfermedad avanzada por VIH” y “células CD4 bajas”. Los criterios de inclusión de los estudios fueron: población adulta; iniciado después de 1996 y publicado antes de julio de 2021; ensayos clínicos, estudios transversales, de cohorte y de casos y controles; estudios que analizan la relación entre EAS y CVRS; idioma inglés o español. Se calcularon diferencias de medias estandarizadas ( d +) para estimar el tamaño del efecto para los metaanálisis. Los efectos promedios se calcularon utilizando un modelo de efectos aleatorios, y el análisis de moderadores utilizando modelos de efectos mixtos. El metaanálisis incluyó 38 estudios. Los resultados indicaron que la CVRS es peor en pacientes con EAS en comparación con aquellos sin EAS. Los principales dominios de CVRS afectados son la percepción de salud general y su preocupación , y la función física y de salud y los síntomas asociados . Encontramos un impacto moderado por edad y género en algunos dominios de CVRS. No encontramos diferencias en cuanto a las desigualdades socioeconómicas, país de residencia o período de tiempo analizado. En conclusión, la enfermedad avanzada por VIH tiene un impacto negativo en la salud y el bienestar en las personas con VIH. Nuestros resultados muestran que, a pesar de todos los avances en los tratamientos antirretrovirales en los últimos 25 años, el EAS persiste como una fuente de extrema vulnerabilidad, independientemente de dónde vivan las personas con VIH.

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Introduction

In 1996, the advent of combined active antiretroviral therapy (cART) dramatically transformed the face of AIDS [ 1 ]. Since then, the efficacy and safety of antiretroviral therapies have improved, while AIDS-related morbidity and mortality have continued to decrease [ 1 ]. In 2014, the World Health Organization (WHO) approved a new goal on HIV and AIDS: “ to end the AIDS epidemic as a public health threat by 2030 ”. To achieve this objective, UNAIDS established the “90-90-90” targets, defined as: “90% of people living with HIV (PLHIV) will know their HIV status, 90% of people who know their HIV-positive status will be accessing treatment, and 90% of PLHIV on treatment will have suppressed viral loads.” This strategy promoted healthy lives and well-being for all PLHIV, regardless of their age or country of residence [ 2 , 3 ]. Recently, these objectives have become more ambitious, raising the bar to ensure that 95% of PLHIV achieve these targets [ 4 ]. Since then, different authors have highlighted the importance of health-related quality of life (HRQoL) for attaining long-term health and well-being in PLHIV, calling on health systems, international societies, and others providing AIDS services to include it as an essential goal of HIV care [ 5 , 6 ].

As a multidimensional concept, HRQoL can be influenced by many factors in PLHIV, including ageing, gender, HIV-related symptoms, comorbidities, substance abuse, depression, socioeconomic inequalities, employment, and financial stress, among others [ 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. Understanding all the factors associated with HRQoL is critical for designing interventions to support PLHIV, especially vulnerable populations such as those accessing services with advanced HIV disease (AHD).

The WHO defines AHD as a CD4 + count under 200 cells/µL or a WHO clinical stage 3 or 4 [ 14 ]. Despite all the efforts to rapidly diagnose HIV infection, diagnosis of AHD is still frequent in PLHIV even in middle- and high-income countries. In 2021, of the 692,000 people in the European Union/European Economic Area who received a new HIV diagnosis, 35% were diagnosed with AHD [ 15 ]. Worldwide, about 650,000 people died from AIDS-related diseases in 2021, over half in the WHO Africa and Asia–Pacific regions [ 16 ].

AHD has a negative impact on the health of PLHIV [ 17 , 18 ], increasing the likelihood of developing AIDS- and non-AIDS-defining disease, especially cancer, cardiovascular disease, kidney disease, and neurocognitive impairment. All these risks predispose those with AHD to experience more physical symptoms, including chronic pain, extreme fatigue, and a significant decline in their ability to carry out activities of daily living [ 19 , 20 , 21 , 22 ]. Moreover, AHD is associated with an increased risk of mortality and reduced life expectancy [ 21 , 23 ]. Managing multiple medical conditions simultaneously can be overwhelming, negatively impacting emotional and psychological quality of life [ 24 ]. Furthermore, the stigma and discrimination associated with HIV may intensify in this advanced stage, leading to social isolation, self-esteem issues, and difficulties in accessing adequate medical care [ 25 ]. All these aspects suggest that AHD has a devastating impact on the physical, mental, and emotional health in PLHIV, ultimately affecting HRQoL.

However, there is no consensus on the impact of AHD on HRQoL. Different authors have reported that PLHIV with low CD4 counts or an AIDS-defining event have worse HRQoL than those with higher CD4 counts or without AIDS. However, there is no agreement about which HRQoL domains are most affected in people with AHD. Regarding CD4 + cells counts, studies by Fuster-RuizdeApodaca et al., Venturi et al., and Aden et al. have reported that lower CD4 counts correspond to lower overall HRQoL scores [ 26 , 27 , 28 ]. Emuren et al. and Liu et al. described that CD4 + cell counts below 200/µL were associated with worse physical but not mental health [ 29 , 30 ]. On the other hand, Fumaz et al., focusing on gender differences, observed that poorer mental health in women was associated with lower CD4 cell counts but not with physical health [ 31 ]. Préau et al. reported similar results in a mixed-gender sample, finding a negative association between low CD4 cells and mental HRQoL [ 32 ]. Regarding AIDS, Emuren et al. and Préau et al. found that an AIDS diagnosis was linked with worse physical health but not with the mental health dimension [ 29 , 33 ], while Fumaz et al. reported that AIDS-defining events were similarly associated with unacceptably low physical and mental HRQoL, regardless of gender [ 31 ]. Nevertheless, Badia et al. did not find any relationship between low CD4 counts or AIDS with lower HRQoL scoring [ 34 ]. The variability of these findings in different settings supports the need to synthesize all available evidence to clarify how AHD affects HRQoL.

Another aspect that warrants investigation is the effect of improvements in antiretroviral therapy (ART) over time. Since its introduction in 1996, ART has made gradual but steady advances in terms of better efficacy, decreased toxicity, and improved convenience. In the first years of the AIDS pandemic, surviving to an AHD diagnosis was the main challenge for PLHIV. In the mid-1990s, treatments with protease inhibitors (PIs) like ritonavir and indinavir plus zidovudine represented a significant breakthrough in the approach to HIV/AIDS, providing an opportunity for people with AHD [ 1 ]. The first PIs were associated with diarrhea, metabolic side effects, and lipodystrophy [ 35 ], while zidovudine, the first nucleoside retrotranscriptase inhibitor (NRTI), was associated with anemia and bone marrow suppression [ 36 ]. Other first-generation NRTIs, such as stavudine, zalcitabine, and didanosine were associated with severe mitochondrial toxicity, peripheral neuropathy, and pancreatitis [ 37 ]. Efavirenz, the first non-nucleoside retrotranscriptase inhibitor (NNRTI), and nevirapine were approved at the end of the twentieth century. Efavirenz was associated with neurotoxicity, while nevirapine could cause severe hypersensitivity hepatitis [ 38 , 39 ]. In the 2000s, the second-generation therapies appeared, including boosted PI, new NRTI, and NNRTI, with greater efficacy, tolerance, and convenience [ 40 ]. These new drugs permitted the development of fixed-dose combination (FDC) therapies, reducing the pill burden and improving adherence. In this second period, PIs were associated with a higher cardiovascular risk [ 41 ], and tenofovir disoproxil-fumarate (TDF) with renal and bone toxicity [ 42 ]. In the mid-2000s, raltegravir, the first integrase strand-transfer inhibitor (INSTI), was approved for the treatment of HIV infection, followed by elvitegravir, dolutegravir, and bictegravir. The introduction of the latest INSTIs marked the third period of antiretroviral treatment, characterized by the widespread use of FDC in therapies and the development of potent bi-therapies for treating HIV infection. INSTIs have been associated with neuropsychiatric toxicity and obesity, but these adverse effects rarely lead to treatment discontinuation [ 43 ]. The success of ART has permitted the establishment of new strategies, such as early treatment of HIV infection regardless of the number of CD4 cells and the “test and treat” strategy, initiating ART as soon as possible [ 44 , 45 ]. These extraordinary changes could support the hypothesis that improvements in ART from 1996 to 2021 have impacted HRQoL even in PLHIV with AHD. Unfortunately, access to remarkable advances in antiretroviral therapy has been disparate worldwide due to the varying availability and allocation of economic resources in different countries [ 46 ].

The aims of this meta-analysis are: (1) to assess the effects of AHD on HRQoL in PLHIV; (2) to analyze the probable changes on HRQoL outcomes over the last 25 years, from the advent of the first cART with PI to the new regimens of ART that use INSTI; (3) to assess heterogeneity among studies; and (4) to evaluate potential differences in HRQoL in PLHIV with AHD from different countries and levels of economic development: low-, middle- and high- income countries, and to examine the influence of other potential variables.

Protocol and Registration

The study protocol was pre-registered on the Open Science Framework (see https://doi.org/10.17605/OSF.IO/RZAMQ for further information). Furthermore, this systematic review and meta-analysis was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA guidelines) [ 47 ]. Supplementary Table 1 presents the PRISMA checklist.

Study Eligibility Criteria

Our study population was adults with AHD defined as AIDS (CDC clinical stage C3 or WHO HIV-clinical stage 3/4), or CD4 < 200 cells/µL [ 14 ]. Inclusion criteria were: (1) studies in PLHIV aged 18 years or older; (2) studies initiated after the advent of cART in 1996, and published before 31 July 2021; (3) clinical trials, cross-sectional, cohort, and case–control studies that included any HRQoL intervention; (4) studies analyzing the relationship between AHD and HRQoL, comparing HRQoL with versus without AIDS and/or with CD4 + lymphocytes ≥ 200 cells/μL versus < 200 cells/μL; (5) studies written in English or Spanish. Exclusion criteria were: (1) meta-analyses, systematic reviews, and secondary studies; (2) abstracts, conference proceedings, books or book chapters, unpublished material, and reports that were not peer-reviewed; (3) articles reporting HRQoL measures obtained using a non-validated questionnaire; (4) articles reporting lymphocyte CD4 + counts, not categorized as having more or less than 200 CD4 + cells/μL.

Search Strategy

The search was conducted from 1 to 31 July 2021 in PubMed and the Web of Science. The following keywords were used: “health-related quality of life” [OR] “HQRoL” AND “HIV” [OR] “AIDS” [OR] “advanced HIV disease” [OR] “low CD4 cells”. Supplementary Table 2 presents the full search strategy. Additionally, the reference lists of the selected articles were handsearched to identify other potentially eligible studies.

Search results were de-duplicated, and four review authors (IPT, JP, JPT and SR) independently screened the titles and abstracts against the selection criteria. All relevant or potentially relevant records were retrieved for full-text review, which was also performed independently by IPT, JP, JPT, and SR. Disagreements were resolved by discussion between the four review authors. Doubts about HRQoL measures or meta-analysis methods were resolved by MJF, an expert in HRQoL, and MRA, an expert in meta-analyses.

Data Extraction and Quality Assessment

Study characteristics were independently extracted by the researchers according to a predefined protocol and categorized based on article characteristics. The following information was collected: first author, publication year, country, World Bank income level, sample size, demographic characteristics of the sample (i.e., age, sex), study design, HRQoL questionnaires, recruitment period, percentage of patients on ART, percentage of patients with undetectable viral load, percentage of patients with CD4 +  < 200 cells/µL, and percentage of patients with AIDS (Table  1 ). Information was also extracted on study funding, authors’ conflict of interests, and other ethical issues.

The methodological quality of the studies included in the meta-analysis was assessed with the Newcastle–Ottawa Scale (NOS), adapted for cross-sectional studies [ 48 ]. This scale uses a “star system” to judge quality based on three dimensions: selection, comparability, and outcome. The NOS consists of 7 items, and the total maximum quality score is 9 stars. Study quality was classified as “high” (8–9 stars), “moderate” (5–7 stars) or “low” (≤ 4 stars).

To assess the reliability of the data extraction, all studies were independently coded by two review authors (IPT and MRA), and inconsistencies were resolved by consensus. For categorical variables, kappa coefficients ranged between 0.810 and 1.0 (M = 0.931), and for continuous variables all intra-class correlations were equal to 1.0.

Computation of Effect Sizes

Usually, HRQoL is measured as a multidimensional concept; however, not all HRQoL questionnaires have exactly the same dimensions. To make the comparison feasible, we categorized the most frequent dimensions according to similarity or by grouping the instruments containing summary indexes. Three review authors (PI, RM, MJF) carried out this process, discussing and resolving discrepancies by consensus. Six outcome domains were finally created: overall health perception and concern , physical and functional health and symptoms , psychological health , social relationships , mental health summary , and physical health summary . Supplementary Table 3 provides details on how dimensions of the questionnaires were categorized.

Once the six HQRoL domains were summarized, the effect sizes for each individual study were calculated. The effect size index was the standardized mean difference ( d ), defined as the difference between the mean of the treatment group and the mean of the control group, divided by a pooled standard deviation (SD): d  = c(m)(yT − yC)∕SD, with c(m) representing a correction factor for small sample sizes [ 49 ]. In this meta-analysis, the d index was calculated to compare the differences in HRQoL between people diagnosed versus not diagnosed with AIDS, and between those with CD4 counts under versus over 200 cells/µL. In any case, the mean values of the non-AIDS and the CD4 ≥ 200 cells/µL groups (control groups) were subtracted from the means for the AIDS and the CD4 < 200 cells/µL groups (treatment groups), respectively, such that negative d values indicate poorer HRQoL in the AIDS and CD4 < 200 cells/µL groups. For standardization, absolute values of d of around 0.2, 0.5, and 0.8 were interpreted as small, moderate, and large magnitudes of effect, respectively [ 50 ]. For effect size calculations, the available means and SDs for each group were used. When this information was not reported, the corresponding authors were contacted to request the required values. In some studies, when the results were reported by means of odds ratio or correlation, conversion formulas were applied to obtain the corresponding d value [ 51 , 52 ].

Statistical Analysis

Separate meta-analyses were carried out with the effect sizes for each of the six outcome measures, for the comparison of the AIDS versus non-AIDS groups, and for the comparison of the CD4 < 200 cells/µL versus CD4 ≥ 200 cells/µL groups.

Random-effects models were used to account for the expected variability in effect sizes. This model involves weighting each effect size by its inverse variance, defined as the sum of the within-study variance and between-study variance, the latter being estimated by restricted maximum likelihood [ 53 ]. For each meta-analysis, the method proposed by Hartung was applied to compute the mean effect size along with its 95% confidence intervals (CI) [ 54 ]. To check the variability in effect sizes, Cochran’s heterogeneity Q statistic and the I 2 index (values of 0%, 25%, 50% and 75% representing no, low, moderate, and high heterogeneity, respectively) were calculated [ 55 ]. For each meta-analysis, a forest plot was also constructed.

Publication bias was assessed by constructing funnel plots using the trim-and-fill method, which consists of imputing missing effect sizes to achieve symmetry [ 56 ]. Furthermore, Egger’s regression test was also applied [ 57 ]. Evidence of publication bias was defined as a statistically significant result for Egger’s test, defined at p  < 0.10 instead of the usual p  < 0.05 because of the lower statistical power with a small number of studies [ 58 ].

Finally, in the presence of heterogeneity and at least 10 studies for the outcome, analyses of potential effect moderators were performed [ 59 ]. Meta-regressions and weighted ANOVAs for continuous and categorical moderators, respectively, were applied by assuming mixed-effect models by means of the F statistic, described by Knapp-Hartung [ 60 , 61 ]. The Q E statistic was calculated to assess the model misspecification of the moderator analyses, together with an estimate of the percentage of variance accounted for by the moderator, R 2 [ 62 ].

All statistical analyses were carried out with the metafor package in R version 3.2.3 [ 63 ].

Characteristics of Included Studies

The search yielded 1079 results in PubMed and 1487 in the Web of Science. After removing duplicates, a total of 1585 unique records were screened, and 531 full-text articles were assessed for eligibility (see Fig.  1 ). After exclusion criteria were applied, 38 studies were included in the meta-analysis. One of these used two samples, so a total of 39 samples were analyzed (Table  1 ; Fig.  1 ) [ 24 , 27 , 28 , 29 , 33 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 ]. According to the assessment with the NOS scale, 18 studies (46.2%) were deemed high quality and 21 (53.8%) moderate quality (Supplementary Table  4 ). All studies met criteria for the ascertainment of the exposure and the assessment of the outcome, as these were inclusion criteria for the study.

Flow chart of study selection process

Mean Effect Sizes and Heterogeneity

Table 2 presents the results of the meta-analysis for the comparison of the groups with CD4 < 200 cells/µL versus CD4 ≥ 200 cells/µL, for each of the six HRQoL outcome domains. Forest plots are displayed in Fig.  2 . The mean effect sizes for all six outcomes were negative, indicating worse HRQoL in the group with lower CD4 counts. All results were statistically significant except for psychological health ( d +  − 0.133, 95% CI − 0.319, 0.054) and mental health summary ( d +  − 0.260, 95% CI − 0.851, 0.332). The highest mean effect size was found for overall health perception and concern ( d +  − 0.598, 95% CI − 0.949, − 0.248), followed by physical and functional health and symptoms ( d +  − 0.395, 95% CI − 0.740, − 0.049) and physical health summary ( d +  − 0.362, 95% CI − 0.557, − 0.167), with similar magnitudes. The meta-analysis showed heterogeneity (I 2 > 70% and statistically significant Q), except for physical health summary , where the I 2 value was 36.7% and Cochran’s Q was not significant (Table  2 ). This large variability is also reflected in the forest plots (Fig.  2 ).

Forest plots displaying the standardized mean differences with 95% confidence intervals for the comparison of the CD4 < 200 cells/μL and CD4 > 200 cells/μL groups for each of the six outcome measures: overall health perception and concern ( A ), physical and functional health and symptoms ( B ), psychological health ( C ), social relationship ( D ), mental health summary ( E ) and physical health summary ( F ). RE (random-effects) model refers to the statistical model used in the calculations

Table 3 presents the results of the meta-analysis comparing AIDS versus non-AIDS groups for each of the six HRQoL outcome measures. Forest plots are displayed in Fig.  3 . As previously, the mean effect sizes were negative for all six outcomes, indicating poor HRQoL in the AIDS group. All analyses were statistically significant with the exception of psychological health ( d +  − 0.136; 95% CI − 0.305, 0.032). In this case, the highest mean effect size was found for physical health summary ( d +  − 0.670; 95% CI − 1.002, − 0.338), while the rest of the mean effect sizes showed a low to moderate magnitude. Regarding the variability among effect sizes, very high heterogeneity was found for all outcomes (I 2  > 80% and statistically significant Q) (Table  3 ; Fig.  3 ).

Forest plots displaying the standardized mean differences with 95% confidence intervals for the comparison of the AIDS with non-AIDS groups for each of the six outcome measures: overall health perception and concern ( A ), physical and functional health and symptoms ( B ), psychological health ( C ), social relationship ( D ), mental health summary ( E ) and physical health summary ( F ). RE (random-effects) model refers to the statistical model used in the calculations

Publication Bias

Publication bias was assessed through Egger’s tests and funnel plots, using the trim-and-fill method. Figure  4 presents the funnel plots for the comparison according to CD4 counts (< 200 cells/µL versus ≥ 200 cells/µL) for the HRQoL measures. For physical health summary , two additional effect sizes were imputed to the original set of estimates to achieve symmetry in the funnel plot (Fig.  4 F). When a mean effect (and its 95% CI) was calculated using the six effect sizes plus the two imputed values, the mean effect was d +  − 0.317 (95% CI − 0.490, − 0.144). However, Egger’s test did not reach statistical significance ( p  = 0.117).

Funnel plots for the comparison of the CD4 < 200 cells/μL and CD4 > 200 cells/μL groups for overall health perception and concern ( A ), physical and functional health and symptoms ( B ), psychological health ( C ), social relationship ( D ), mental health summary ( E ) and physical health summary ( F ) measures. The white circles are the imputed standardized mean changes by means of the Duval and Tweedie's trim and-fill method

Figure  5 presents the funnel plots for the comparison of the AIDS versus non-AIDS groups. For social relationships , four additional effect sizes were imputed to achieve symmetry in the funnel plot (Fig.  5 D). When a mean effect (and its 95% CI) was calculated using the 13 effect sizes plus the four imputed values, the mean effect was d +  − 0.083 (95% CI − 0.262, 0.095). Nevertheless, once again Egger’s test was not statistically significant ( p  = 0.61).

Funnel plots for the comparison of the AIDS with non-AIDS groups for overall health perception and concern ( A ), physical and functional health and symptoms ( B ), psychological health ( C ), social relationship ( D ), mental health summary ( E ) and physical health summary ( F ) measures. The white circles are the imputed standardized mean changes by means of the Duval and Tweedie's trim and-fill method

For the rest of meta-analyses, the trim-and-fill method did not require imputing new values to the funnel plots (Figs. 4 , 5 ), and the Egger’s tests were not statistically significant. Thus, the results of these meta-analyses are at low risk for publication bias.

Analysis of Moderator Variables

The heterogeneity observed in the standardized mean differences prompted an analysis of moderator variables for outcome measures with at least 10 studies. Tables 4 and 5 show the results of the meta-regressions, and Tables 6 and 7 of the weighted ANOVAs, comparing groups by CD4 counts and AIDS status, respectively.

Of the different potential moderator variables analyzed, only two continuous variables yielded a statistically significant result for the comparison of the CD4 groups (see Table  4 ): mean age exhibited a statistically significant relationship with the effect size for overall health perception and concern ( p  = 0.038), accounting for 35.5% of the variance observed. The negative sign of the regression coefficient for this moderator indicated larger standardized mean differences, as the mean age of participants decreased for this outcome measure. On the other hand, the percentage of men showed a significant relationship with the effect sizes of the social relationships measure ( p  = 0.042), accounting for 30.8% of the variance. Once again, a negative relationship was found, such that the larger the proportion of men, the lower the standardized mean differences for this outcome measure.

Finally, for the comparison of groups with AIDS versus without AIDS, country income level yielded a marginally significant result ( p  = 0.059) as an effect modifier, explaining a notable percentage of the variance ( R 2  = 38.21%) for the physical and functional health and symptoms measure (see Table  7 ). The highest effect was found in the low-income category ( d +  − 0.786).

We conducted a meta-analysis to assess the influence of AHD on HRQoL and its different domains. We included papers published over the last 25 years of the AIDS pandemic, analyzing possible differences in HRQoL and AHD in different periods of time as well as differences between countries of different income levels. Our main finding was that HRQoL is worse in patients with AHD compared to those without. People with CD4 counts of fewer than 200 cells/µL sustain negative impacts in all domains of HRQoL, especially in overall health perception and concern , followed by physical and functional health and symptoms , and physical health summary , with similar mean effect sizes but large inter-study variability. The outcomes related to psychological health and mental health summary were also negatively affected, though comparisons did not reach statistical significance. In patients with an AIDS diagnosis, the six HRQoL domains showed lower scores than in those without AIDS. The greatest difference was observed for physical health summary . As in patients with low CD4 cells, psychological health scores did not show a significant difference between people with versus without AIDS. This finding is probably related to the negative psychological impact of an HIV diagnosis on mental health in PLHIV, regadless of AIDS diagnosis or number of CD4 cells [ 96 , 97 ]. PLHIV often experience intersecting types of discrimination (marginalized identities, internalized HIV stigma, limited economic resources, etc.) or suffer from uncertainty about a non-curable and potentially lethal infection. Thus, PLHIV are highly vulnerable to mental health problems [ 98 , 99 ], independently of their immunovirological status.

In this meta-analysis, we found that overall health perception and concern and physical and functional health and symptoms are the main HRQoL domains affected in PLHIV with AHD. Physical and functional health and symptoms includes different dimensions, including physical functioning, energy, mobility, effects and severity of pain, and level of independence. The symptomatology of advanced stages of HIV infection, the associated comorbidities, and the loss of vitality caused by progression of HIV infection could explain the worse scores in these domains [ 19 , 20 , 21 , 22 ].

Our meta-analysis considers numerous effect modifiers (age, gender, treatment with ART, and HIV viral load) that were analyzed for their potential influence on the effect sizes of the HRQoL outcome. We found a moderate impact for age and gender on some HRQoL domains. Age showed an inverse relationship with the effect sizes for overall health perception and concern , such that older age was associated with worse scores, probably due to ageing, comorbidities, and disability associated with AHD [ 100 ]. The domain for overall health perception and concern comprises perceptions, distress, concerns, and worries related to general health. Thus, this result is consistent with previous studies showing that HRQoL indexes of physical health are negatively affected in older PLHIV [ 101 ]. Furthermore, male sex showed a significant negative relationship with the effect sizes for social relationships . In high-income countries, men with HIV are usually reported as having better scores in social relationships and other related dimensions or predictors than women with HIV [ 27 , 31 ]. Our results shows that this trend could differ between countries depending on income level, that AHD could affect men’s social relationships more than women’s, or that in low- and medium-income countries women use social support as coping strategy to reduce the stressors on health outcomes [ 8 , 102 ]. Another possibility is that men are overrepresented in this meta-analysis, especially in studies from low- and middle-income countries.

Regarding the relationship between HRQoL and country income level, we hypothesized that people with AHD from middle- or high-income countries would report higher HRQoL scores than in those living in low-income countries, due to the direct impact of socioeconomic status on HRQoL [ 8 ]. However, we did not find differences between the analyzed countries according to this parameter. When we compared the group with versus without AIDS, we found only a borderline significant result for physical and functional health and symptoms , in PLHIV with AIDS from low-income countries. These results could be related with worse conditions in housing, nutrition, health resources, employment difficulties, and other socioeconomic indicators in these settings [ 88 , 95 ]. In fact, there is evidence supporting the degenerative impact that material deprivation has on HRQoL [ 103 ].

Furthermore, given the continuous improvements in the efficacy and safety of ART from 1996 to the present, we hypothesized that HRQoL in PLHIV with AHD in the era of the new ART (2012–2019) would be better than when these drugs were first introduced (1996). We analyzed three 8-year periods: 1996–2003, 2004–2011, and 2012–2019. Surprisingly, we observed no differences between the time periods analyzed. AHD continues being the worst condition in the spectrum of HIV infection, occurring in high-income and low-income countries alike, despite the availability of new antiretroviral treatments, early diagnosis strategies, and easy access to ART. Ghiasvand et al.’s meta-analysis of studies from 2005 to 2016 in low-, middle- and high-income countries likewise found no impact on HRQoL from ART in PLHIV [ 103 ]. The present meta-analysis broadens this evidence by also including earlier periods with less effective and more toxic treatments in PLHIV with AHD. These results suggest that improving quality of life for PLHIV may require additional interventions beyond just the provision of ART.

To address the significant impact of AHD on HRQoL, the initial step should be the implementation of prevention programs, early diagnosis, and early treatment to decrease the prevalence of AHD worldwide [ 44 ]. Regarding strategies to enhance HRQoL in PLHIV, these should first focus on addressing basic needs such as nutrition, access to healthcare resources, and employment, which have been associated with low HRQoL [ 6 , 95 ]. This is particularly crucial in low-income countries, where inequalities are often more pronounced and require steadfast policy responses. Indeed, a systemic and comprehensive approach that considers the special individual needs of this population is essential everywhere. This should include bolstering resilience resources, economic empowerment, and self-stigma detection. Moreover, PLHIV with AHD need preventive interventions that focus on both AIDS and non-AIDS events, among other aspects [ 6 ]. Other strategies should provide health education along with comprehensive disease management information and training to ensure adherence to ART, thereby empowering patients to effectively participate in controlling their disease [ 76 ]. Emotional support services and counseling should be offered to manage stress and other psychological challenges [ 29 ]. Encouraging participation in support groups, social activities, and community programs is also crucial for reducing loneliness [ 74 ]. Additionally, efforts should be directed towards eradicating the stigma associated with AHD while promoting inclusivity and understanding for PLHIV in society [ 25 ]. To achieve all these goals, individuals with AHD should receive multidisciplinary, comprehensive, and personalized care from a team of physicians, nurses, social workers, and psychologists.

Our study has some limitations. First of all, we could only make use of data available from published studies. Second, we were unable to explore the influence of some factors associated with reduced HRQoL: intravenous drug use or substance misuse, socioeconomic inequalities, refugee or migrant status, lower educational level, social support, and internalized stigma [ 104 ]. Third, some countries and WHO regions are underrepresented. We did not find data from Latin America (except from Mexico and Guyana), eastern Europe countries, the Western Pacific and Eastern Mediterranean regions (except Pakistan), India, Brazil, or others. The languages used in this meta-analysis (Spanish or English), along with the databases chosen (PubMed and the Web of Science, both dominated by research from Western countries) probably generated some selection bias in the included studies.

On the other hand, the review also has some important strengths. First, we obtained enough data to demonstrate the highly negative impact of AHD on HRQoL. Second, the long study period enabled a comparison of HRQoL in different periods of the AIDS pandemic and in countries with different income levels. Its results show that despite all the advances in the treatment of HIV infection over the last 25 years, AHD persists as a source of extreme vulnerability for PLHIV.

In conclusion, this meta-analysis shows that AHD has a negative impact on the health and well-being of PLHIV, affecting all HRQoL domains, especially overall self-perceived health, physical health summary, and psychological health. These effects have not changed in the last 25 years and affect all PLHIV with AHD independently of country of residence. HIV clinicians and researchers should focus future studies on improving HRQoL and better understanding the special needs of this vulnerable population.

Data Availability

Dataset is available upon request.

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We acknowledge people living with HIV who have contributed to each study included.

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Advances in HIV Prevention and Treatment: A Literature Review

Joseph N. Inungu1*, Daudet Ilunga Tshiswaka2, Daryn Papenfuse1  

1 School of Health Sciences, Central Michigan University, Mount Pleasant, MI, USA

2 Department of Public Health, University of West Florida, Pensacola, FL, USA

* Corresponding author: Joseph N Inungu, School of Health Sciences, Central Michigan University, Mt Pleasant, MI, USA. Tel: +1-9897744476, Fax: +19897742908; Email: [email protected]

Received Date: March 25, 2017; Accepted Date: 25 April, 2017; Published Date: 02 May, 2017

Citation: Inungu JN, Tshiswaka DI, Papenfuse D (2017) Advances in HIV Prevention and Treatment: A Literature Review. Curr Res HIV 2017: CRHA-111. DOI: 10.29011/2575-7105. 100011

Background:  The last decade has witnessed several advances in the management of HIV/AIDS with the development of potent and safe antiretroviral drugs and new HIV prevention technologies.

Objective:  This review summarizes the recent advances in the management of the HIV infection .

Methods:  Medline via PubMed and Google search engine were searched for articles dealing with antiretroviral therapy and new prevention technologies.

Results:  The understanding of the lifecycle of the HIV was a turning point that provided researchers with the knowledge and tools needed to prosecute drug discovery efforts focused on targeted inhibition with specific pharmacological agents. New prevention technologies continue to expand the current toolbox, transforming HIV/AIDS from an inevitable lethal disease into a manageable condition. The integration of behavioral, biomedical and structural interventions will likely reduce the incidence of HIV while promising new leads for an effective HIV vaccine keep the hope of a world free of HIV alive.

Conclusion:  Although the fight against HIV has been long and arduous, many signs seem to suggest that ending HIV epidemic is not only possible; it is well in our reach.

Keywords: Antiretroviral Therapy; HIV/AIDS; HIV Prevention Technology;Lifecycle

Introduction

Three decades following the report about a cluster of Kaposi’s sarcoma and Pneumocystis pneumonia among homosexual men in Los Angeles and New York, [1] HIV/AIDS remains a global public health challenge. Approximately 36.7 million people were living with HIV/AIDS (PLH) worldwide at the end of 2015. An estimated 2.1 million people became newly infected with HIV and 1.1 million died from AIDS-related illnesses during the same year. The vast majority of people living with HIV are in low and middle income countries. Sub-Saharan Africa is the most affected region, with an estimated 25.6 million people living with HIV in 2015. About 66% of new HIV infections in 2015 occurred in sub-Saharan Africa [2]. Unprecedented efforts of the last thirty years have turned human immunodeficiency virus infections from terrifying lethal diseases to manageable conditions [3]. Combination antiretroviral therapy dramatically reduces the viral load to an undetectable level (

The impact of the HIV pandemic on women is rising, even in countries where other routes of transmission are more prevalent [5]. Women have few options to protect themselves from acquiring HIV. Efforts to promote abstinence, monogamy and the use of condoms have not been enough to stop the epidemic nor are these approaches practical in many settings [6]. Women face difficulties convincing their male partners, especially husbands and regular partners, to use condoms or to be monogamous or faithful. Female condoms, developed as an alternative to give more control to women to protect themselves, are not widely accepted. Structural issues and high cost have hampered their use. HIV Pre-Exposure Prophylaxis (PrEP) provides a promising new approach for slowing the spread of HIV in the United States [7].However, Prep is not widely available globally [8], limiting the number of options to women to protect themselves against HIV. The development of products applied inside the vagina or rectum to protect against HIV commonly called microbicides provide great potential for a female-controlled, preventive option, which would not require negotiation, consent or even knowledge of the partners [9]. Microbicides could benefit both men and women. The successful utilization of this preventive method depends on its efficacy and its acceptability.

The discovery of an effective vaccine remains the goal of HIV research. Vaccine technologies have evolved significantly in the last decade. Reports that the prime/boost combination of two vaccines (ALVAC (R) HIV and AIDSVAX(R) B/E) lowered the rate of HIV infection by 31.2 percent in more than 16,000 volunteers in Thailand demonstrated that the development of an effective preventive HIV vaccine is scientifically possible. This discovery has reinvigorated and raised hope among researchers. This review was undertaken to describe promising new initiatives in our continued efforts to fight the HIV epidemic. This update will keep knowledge about HIV/AIDS current among community organizers, health educators and policy makers.

1. Methods Search strategy Medline via PubMed and Google search engine were searched for relevant articles published between January 2007 and April 2017. The key search terms applied included: “Lifecycle” or “Antiretroviral therapy” or “New Prevention technologies” or “HIV Vaccines” and "HIV”. The formal review process was further informed by searches of published research and technical reports from peer-reviewed journals presented at scientific conferences and reference lists from publications of interest. Some grey literature including conference presentations, project reports, government reports, and released by international organizations such as UNAIDS and the World Health Organization were also considered.

      1.1 Inclusion Criteria

Original articles published in English and covering any of the above-mentioned keywords regardless of the country were considered for this review. Articles published in any language other than English were excluded. Methods of assessment of documents Citations were examined, titles and abstracts were screened for eligibility. Selected citations were classified as either:

• Primary citations qualifying for inclusion in the synthesis or
• Not relevant citations not included in this study.

Full texts were reviewed in greater detail if deemed relevant, and findings pertinent to this literature review were included in this article.

   2.1 HIV/AIDS Treatment

      2.1.1 Mechanisms of Action of Antiretroviral Drugs

The discovery of the causative agent of AIDS together with the understanding of the virus replication cycle were instrumental in assisting researchers to prosecute drug discovery efforts focused on targeted inhibition with specific pharmacological agents [10]. ( Figure 1) summarizes the HIV life cycle. To multiply, the HIV virus infects only cells that carry CD4 receptors on their surface, such as T4-lymphocytes, monocytes and macrophages, glial cells in the brain, chromaffin cells in the intestines and Langerhans' cells in the skin [11]. TheCCR5 or CXCR4 antagonists are antiretroviral drugs that can prevent the viral attachment to the CD4 T-cells.

Once the HIV binds to a CD4+ surface receptor, it activates other proteins on the surface of the human cell known as CCR5 and CXCR4 to allow the HIV envelope and CD4 cell membrane to fuse. A second group of drugs can interfere with the fusion process (Fusion inhibitors). Once inside the cell, the viral capsid that contains the RNA and important enzymes is released into the host cell (Uncoating). A viral enzyme called reverse transcriptase converts its genetic material, HIV RNA into HIV DNA, allowing HIV to enter the CD4 cell nucleus. Reverse transcription can be blocked by NucleosideReverse Transcriptase Inhibitors(NRTIs) and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs). The newly formed viral DNA is then integrated with the DNA of the human host cell using a viral enzyme called integrase (Integration). The Integrase inhibitors can block the integration phase. Once integrated into the CD4 cell, the CD4 machinery produces long chains of HIV proteins (replication). A viral enzyme called protease cuts these long chains of proteins into smaller proteins to form the structure of the new HIV particle, including each of the enzymes and proteins needed to repeat the reproductive process [12].

Once the new viral particles are assembled, they bud off the host cell and can infect other cells. Protease inhibitors can block viral assembly.

      2.1.2 Classes of A ntiretroviral Drugs

The FDA approved the first antiretroviral drug, zidovudine (AZT), to treat people infected with HIV/AIDS on March 19, 1987 [13]. Since the advent of the first HIV-1 specific antiviral drugs given as monotherapy, significant progress has led to the development of more than 25 FDA-approved antiretroviral drugs. The 6 classes of ARVs include: The Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs), Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs), Protease Inhibitors (PIs), a Fusion Inhibitor (FI), a CCR5 antagonist, and Integrase Strand Transfer Inhibitors (INSTIs). Other drugs including Ritonavir (RTV) and Cobicistat (COBI) are used to improve the Pharmacokinetic (PK) profiles of some ARV drugs (e.g., PIs and The INSTI Elvitegravir (EVG) [14]. (Table 1) presents the antiretroviral drugs used in the treatment of HIV infection. The description of individual drug is beyond the scope of this paper.

HIV Clinicians and patients may select a regimen based on several considerations including antiviral potency, short- and long-term adverse effects, ease of administration, drug interactions, risk of resistance and cost [15].To address the complexity in HIV management in terms of initiating, switching and discontinuing the Anti-Retroviral Treatment (ART), a panel of experts in HIV research and patient care recommended that all HIV-infected individuals with detectable viremia, regardless of their CD4 cell count, should begin ART as soon as possible after diagnosis to prevent disease progression, improve clinical outcomes and limit transmission [16]. They recommended that the initial regimen should consist of 2 Nucleoside Reverse Transcriptase Inhibitors (NRTIs) plus an Integrase Strand Transfer Inhibitor (InSTI). They also made recommendations for special populations (e.g. pregnant women, hepatitis B/C virus coinfection) and for context of acute opportunistic infections [15]. Study data supports switching therapy in some patients because of virologic failure, drug resistance or more adverse or toxic effects [17]. For the good management of PLH, the panel of experts in HIV research and patient care recommend that CD4 cell count, plasma HIV RNA, serum chemistries and estimated creatinine clearance be done as close to the time of HIV diagnosis as possible and prior to beginning ART. Strict adherence to antiretroviral therapy is key to sustained HIV suppression, reduced risk of drug resistance, improved overall quality of life, and survival, [18] as well as decreased risk of HIV transmission [19].

   2.2 HIV/AIDS Prevention

Effective HIV prevention requires a combination of behavioral, biomedical and structural intervention strategies [20]. The early initiation of antiretroviral therapy has been shown to reduce rates of sexual transmission of HIV-1 and clinical events, indicating both personal and public health benefits from such therapy[19].The evidence to support the use of Antiretroviral Therapy (ART) for prevention of new HIV infection in the form of Pre-exposure Prophylaxis (PrEP) among men who have sex with men, transgender, people who inject drugs, heterosexual men and women and HIV-1 serodiscordant couples, or Treatment as Prevention (TasP) for sero

Discordant couples have also grown [21].  

      2.2.1 Biomedical Intervention

         2.2.1.1 Prevention of Mother-to-Child Transmission

The first success of ART has been in preventing mother-to-child transmission of HIV Prevention of Mother-To-Child Transmission (PMTCT) of HIV in the United States and Europe has been a tremendous success, such that transmission rates of less than 2% have been achieved [22].

         2.2.1.2 therapy as prevention.

Though long suspected that treatment reduces an individual’s viral load resulting in decreased risk of HIV transmission, the HIV Prevention Trials Network 052 (HPTN 052) study was the first to conclusively prove this theory. Early initiation of ART (when cell counts are greater than 350) by HIV-infected individuals reduced the

risk of HIV transmission to the uninfected sexual partners by 96 percent compared to initiation when CD4 counts were

         2.2.1.3 Pre-Exposure and Post Exposure Prophylaxis        

Pre-Exposure Prophylaxis (PrEP), is the concept of HIV-negative individuals taking HIV ART to prevent the acquisition of HIV. The use of an ART for PrEP was approved by the United States Food and Drug Administration (FDA) in July 2012 and has been shown to be safe and effective through the Global iPrEx and Partners Prep studies [25].

There is evidence that Post Exposure Prophylaxis (PEP) can reduce the risk of HIV transmission [26]. PEP is an emergency intervention designed to abort HIV acquisition in the event of occupational (i.e., needle stick or mucous membrane splash) or no occupational (i.e., sexual or injecting drug use) exposure to HIV-infected blood or potentially infectious bodily fluids [27].

         2.2.1.4 HIV Testing and Counseling

Early knowledge of one’s positive HIV sero status maximizes opportunities for the person to access care, thereby greatly reducing HIV-related morbidity and mortality, and/or preventing transmission of HIV. Meta-analyses find that PLH who are aware of their sero status are at least half as likely to engage in risky sexual behaviors compared to those unaware PLH [28]. HIV testing is the cornerstone for HIV prevention.

         2.2.1.5 Male and Female Condoms

When used consistently and correctly, male condoms can be highly effective in preventing Sexually Transmitted Diseases (STDs) including HIV [29]. However, they provide less protection against STDs spread through skin-to-skin contact like human papillomavirus (genital warts), genital herpes, and syphilis. Although the  female condom  has been on the market for more than ten years, adoption by end-users, providers, national governments, and donors has remained low. The high price and certain technical characteristics are often cited as the primary obstacles for end-user adoption [30].

         2.2.1.6 Diaphragmes

There is considerable interest in developing new multipurpose prevention technologies to address women's reproductive health needs. Dapivirine-releasing diaphragm with daily release quantities potentially can prevent HIV transmission [31].

         2.2.1.7 Male Circumcision

Three large Randomized Controlled Clinical Trials (RCTs) conducted in South Africa, Kenya and Uganda showed that medical circumcision significantly reduced male participants’ HIV infection risk, ranging from 48% to 61% [32-35]. In addition, circumcision was shown to be associated with a significantly reduced risk of urinary tract infection [35]. Circumcision, however, has not shown a significant protective effect against HIV acquisition among Men Who Have Sex with Men (MSM). 

         2.2.1.8 Microbicides

After several disappointing microbicide trials that failed to show protection against HIV infection, [36,37] the results of the Centre for the AIDS Program of Research in South Africa - the CAPRISA 004 trial - demonstrated that a vaginal microbicide gel containing tenofovir reduced the risk of HIV infection for women by 39% (95% CI: 6, 60) [38]. Building on that experience, the NIH-ASPIRE study, also known as MTN-020, showed that a vaginal ring that continuously releases the experimental antiretroviral drug Dapivirine provided a modest level of protection against HIV infection in women with an overall effectiveness of 31 percent [39]. Microbicides may also be preferable to condoms as an HIV prevention option for some women because women would not have to negotiate their use, as they often must do with condoms.

      2.2.2 Behavioral Interventions

Given the challenges of further reducing HIV infection rates and developing an effective vaccine, it is critical to focus on behavioral prevention efforts that are based on the best available scientific evidence [40]. Behavioral interventions have been shown to decrease sexual risk behaviors [41] and increase condom use [42]. The compendium of effective HIV prevention interventions exists [43]. Sister-to-Sister is a brief (20-minute), one-on-one, skill-based HIV/STD risk-reduction behavioral intervention for sexually active African American women 18 to 45 years old that is delivered during a routine medical visit. Sister-to-Sister is designed to provide intensive, culturally sensitive health information to empower and educate women in a clinical setting; help women understand HIV/STD risk behaviors; and enhance women’s knowledge, beliefs, motivation, confidence, and skills to help them make behavioral changes that will reduce their risk [44].

      2.2.3 Structural Interventions

Macroeconomic and social forces such as poverty, racism, sexism and homophobia, help fuel HIV epidemics, although the pathways between these forces and HIV infection are complex and not always clear [45,46]. Structural interventions seek to address social, economic, political or environmental factors that make individuals or groups vulnerable to HIV infection. For example, laws that criminalize same-sex relationships often hinder men who have sex with men from accessing condoms. A lack of infrastructure, such as transport, prevents many people from accessing health clinics. By successfully addressing these structural barriers, individuals are empowered and able to access HIV prevention services [47].

One example of structural intervention is the Needle and Syringe Programs (NSPs). NSPs are a type of harm reduction initiative that provide clean needles and syringes to people who inject drugs (sometimes referred to as PWID). NSPs are offered at fixed or mobile sites. Fixed sites are typically located where the drugs are bought and sold openly. At fixed sites, additional services such as healthcare services alongside testing and counselling for HIV and other blood-borne viruses [48]. Outreach programs may include mobile units (such as a van or bus), backpacking services on the street or even home deliveries. NSPs substantially and cost effectively reduce the spread of HIV among PWID and do so without evidence of exacerbating injecting drug use at either the individual or societal level [49].

Despite the promise of structural interventions and donor enthusiasm for additional efforts in their implementation and evaluation, less data has been collected on structural interventions than on biomedical and behavioral interventions. Few currently existing programs have been rigorously evaluated against biological outcomes, such as HIV biomarkers [50].

   2.3 HIV Vaccine

The discovery of an effective vaccine remains the ultimate goal of HIV research. However, several factors have contributed to slowing the international efforts to develop an effective HIV vaccine. The number of circulating viral strains is one of the most intractable obstacles to vaccine development. Extremely rapid and error-prone replication yields a large number of mutant genomes, some of which are able to escape immune control [51]. Another major obstacle is the lack of clear immune correlates of protection in humans.

Hard fought advances in basic and clinical research are raising new hope. First, vaccine technology has evolved significantly in the last decade, profoundly changing the future of vaccine development. Reports that the prime/boost combination of two vaccines (ALVAC (R) HIV and AIDSVAX(R) B/E) lowered the rate of HIV infection by 31.2 percent in more than 16,000 volunteers in Thailand demonstrating that the development of an effective preventive HIV vaccine is scientifically possible. Recent advances in isolating broadly neutralizing antibodies and designing new tools and technologies for vaccine delivery have enhanced hope and reinvigorated vaccine discovery efforts [52]. Investigation into additional therapeutic approaches led to the use of gene therapy aimed at a diverse list of disorders including arthritis, HIV infection, dozens of different types of cancers and extremely rare genetic diseases [53].

   2.4 The Future of HIV/AIDS

      2.4.1 Long Lasting Antiretroviral therapy

Although antiretroviral drugs provide durable control of virus replication in many patients, they are not devoid of unwanted secondary effects including long-term side effects, the emergence of multidrug resistance and transmission of drug-resistant HIV strains. Further simplification of treatment and identification of more effective drug combinations are needed to improve patient adherence, the most significant cause of treatment failure. New mechanisms to deliver long-acting ART are being studied and present the potential to improving adherence to treatment and optimizing HIV care [54].

      2.4.2 Shock and Kill

Combinatory antiretroviral therapy increases the survival and quality of life of HIV-1-infected patients. However, interruption of therapy almost invariably leads to the re-emergence of detectable viral replication because HIV-1 persists in viral latent reservoirs. Improved understanding of the molecular mechanisms involved in HIV-1 latency has paved the way for innovative strategies that attempt to purge the latent virus[55].One strategy termed “shock and kill” is aimed at decreasing the numbers of latently infected cells after the activation of HIV transcription in order for host cells to produce HIV-1 proteins (shock); this will presumably allow the cells to be cleared by virus-associated cell death or by a host response (kill) [54].A wide variety of compounds are under investigation as candidate Latency-Reversing Agents (LRAs) for the shock step. Latency-Reversing Agent (LRA) combinations exhibit such a potent effect and represent a proof-of-concept for the co-administration of two different types of latency-reversing agents as a potential strategy to reduce the size of the latent HIV-1 reservoirs [56]. The ongoing BCN02 trial adds three doses of R omidepsin  between the initial and the final vaccine boosts. This cancer drug can activate hidden HIV reservoirs, making it easier for the immune system to eliminate latent viruses [54].

      2.4.3 New Tools and Technologies for Vaccine Delivery

Developing safe, effective and affordable HIV vaccines is the best hope for ending the HIV/AIDS pandemic. Advances in HIV vaccine development-including the design of new tools and technologies for vaccine delivery-have boosted optimism in the field about the prospects for the development of a safe and effective HIV vaccine. The identification of dozens of broad spectrum antibodies that neutralize a wide spectrum of HIV variants circulating around the world is a major step against the constant ability of the virus to mutate. The cell immunity can be stimulated using a new antigen delivery mechanism. Recombinant vaccines rely on the capacity of one or multiple defined antigens to induce immunity against the pathogen, when administered in the presence of adjuvants or when expressed by plasmids or harmless bacterial/viral vectors [57].

This study was undertaken to advances in the management of the HIV infection. This review showed how unprecedented efforts in the fields of biology, pharmacology, and clinical care led to the development of several antiretroviral agents.  As a result, the HIV/AIDS causing retrovirus has gone from being an untreatable infectious agent to one eminently susceptible to a range of approved therapies. Approximately thirty antiretroviral agents with different mechanisms of action, formulated either singly or in combination, are available today to treat patients with Human Immunodeficiency Virus (HIV-1).

Despite the impressive results of antiretroviral drugs, HIV-1/AIDS pandemic remains a challenge. While antiretroviral drugs are widely accessible in rich-country, they are not accessible by every PLH, especially those living in developing countries. Current coverage shortfalls, combined with the relentless expansion of the epidemic, underscore the need for effective prevention interventions to control HIV epidemic. Promoting the utilization of condoms, performing male circumcision in poor communities, and making clean needles available to injecting drug users are few interventions known to be effective. They can be easily integrated to curb the spread of HIV in poor countries.

People living with HIV are expected to take antiretroviral therapy for the rest of their lives in order to prevent viral replication and hopefully prevent opportunistic infections. However, long term ARV therapy increases the risk for cardiac and metabolic side-effects, including dyslipidemias, insulin resistance, and abnormal body fat re-distribution (lipodystrophy, which can lead to increased risk for heart disease and type 2 diabetes. Treatment of these chronic health conditions will require additional resources in an already financially challenged health system.

Integrated provirus in memory T cells, dendritic cells, macrophages, and microglia, that persists for long periods, makes true HIV-1 eradication difficult with available technologies. However, Latency-Reversing Agent (LRA) combinations is a promising strategy to reduce the size of the latent HIV-1 reservoirs.

This review found that when the viral load becomes and stays undetectable with successful treatment, the risk for sexual transmission of HIV is negligible. The public health implication of this knowledge underscores the needs for governments in countries hit hard by the HIV epidemic to do every effort to make antiretroviral therapy available to as many HIV-infected people as possible. A concern that low educated people may not adhere to the regimen and give rise to virus resistance has not materialized in sub-Saharan Africa.

Several approaches have been tried to fight HIV epidemic. Gene therapy and viral mediated therapy are few methods that have been used. Regardless of their outcome relative to HIV infection, knowledge gained in the fight against HIV epidemic could have indirect benefit. Lessons learned could be applied to treat other conditions. For example, knowledge in the development gained in the development of an HIV vaccine contributed to the rapid development of the Ebola vaccine. Other techniques are now being used to treat cancer.

This review is by no means a daily account of events that occurred from the discovery of the new disease till today. It highlighted what the authors considered important to provide a broad picture of the important achievement in the fight against HIV/AIDS. The fact that only papers published in English were reviewed, other important events may have been overlooked.

The fight against HIV epidemic has been hard, long and expensive. Yet, progress has been made and the end of the tunnel is perceptible. The HIV prevention toolbox continues to grow steadily, allowing clinicians to safely prevent and treat HIV infection. While waiting for the advent of the magic bullet to cure HIV infection, the combination of behavioral, structural and biomedical interventions can prevent the incidence of new HIV cases, but also prevent the occurrence of opportunistic infections and improve the quality of life for people living with HIV. Efforts are currently being made to address disparities that persist for the attainment of the 90-90-90 targets, which are that 90% of people living with HIV know their HIV status, 90% of people who know their HIV-positive status are accessing treatment and 90% of people on treatment have suppressed viral loads by 2020 [58].

Conflict of Interest

The authors certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

Acknowledgements

We are immensely grateful to Robert Brown for designing the HIV life cycle for this manuscript. We also thank Jennifer Rundles, the librarian from Central Michigan University, for assisting the authors in the database search.

Figure1: HIV Lifecycle.

  Table 1: FDA-Approved Antiretroviral Drugs. Adapted From: Antiretroviral Drugs Used in the Treatment of HIV Infection , U.S. FDA.  

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• Published: 24 November 2021

A study of awareness on HIV/AIDS among adolescents: A Longitudinal Study on UDAYA data

• Shobhit Srivastava   ORCID: orcid.org/0000-0002-7138-4916 1 ,
• Shekhar Chauhan   ORCID: orcid.org/0000-0002-6926-7649 2 ,
• Ratna Patel   ORCID: orcid.org/0000-0002-5371-7369 3 &
• Pradeep Kumar   ORCID: orcid.org/0000-0003-4259-820X 1  

Scientific Reports volume  11 , Article number:  22841 ( 2021 ) Cite this article

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Acquired Immunodeficiency Syndrome caused by Human Immunodeficiency Virus (HIV) poses a severe challenge to healthcare and is a significant public health issue worldwide. This study intends to examine the change in the awareness level of HIV among adolescents. Furthermore, this study examined the factors associated with the change in awareness level on HIV-related information among adolescents over the period. Data used for this study were drawn from Understanding the lives of adolescents and young adults, a longitudinal survey on adolescents aged 10–19 in Bihar and Uttar Pradesh. The present study utilized a sample of 4421 and 7587 unmarried adolescent boys and girls, respectively aged 10–19 years in wave-1 and wave-2. Descriptive analysis and t-test and proportion test were done to observe changes in certain selected variables from wave-1 (2015–2016) to wave-2 (2018–2019). Moreover, random effect regression analysis was used to estimate the association of change in HIV awareness among unmarried adolescents with household and individual factors. The percentage of adolescent boys who had awareness regarding HIV increased from 38.6% in wave-1 to 59.9% in wave-2. Among adolescent girls, the percentage increased from 30.2 to 39.1% between wave-1 & wave-2. With the increase in age and years of schooling, the HIV awareness increased among adolescent boys ([Coef: 0.05; p  < 0.01] and [Coef: 0.04; p  < 0.01]) and girls ([Coef: 0.03; p  < 0.01] and [Coef: 0.04; p  < 0.01]), respectively. The adolescent boys [Coef: 0.06; p  < 0.05] and girls [Coef: 0.03; p  < 0.05] who had any mass media exposure were more likely to have an awareness of HIV. Adolescent boys' paid work status was inversely associated with HIV awareness [Coef: − 0.01; p  < 0.10]. Use of internet among adolescent boys [Coef: 0.18; p  < 0.01] and girls [Coef: 0.14; p  < 0.01] was positively associated with HIV awareness with reference to their counterparts. There is a need to intensify efforts in ensuring that information regarding HIV should reach vulnerable sub-groups, as outlined in this study. It is important to mobilize the available resources to target the less educated and poor adolescents, focusing on rural adolescents.

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Introduction.

Acquired Immunodeficiency Syndrome (AIDS) caused by Human Immunodeficiency Virus (HIV) poses a severe challenge to healthcare and is a significant public health issue worldwide. So far, HIV has claimed almost 33 million lives; however, off lately, increasing access to HIV prevention, diagnosis, treatment, and care has enabled people living with HIV to lead a long and healthy life 1 . By the end of 2019, an estimated 38 million people were living with HIV 1 . More so, new infections fell by 39 percent, and HIV-related deaths fell by almost 51 percent between 2000 and 2019 1 . Despite all the positive news related to HIV, the success story is not the same everywhere; HIV varies between region, country, and population, where not everyone is able to access HIV testing and treatment and care 1 . HIV/AIDS holds back economic growth by destroying human capital by predominantly affecting adolescents and young adults 2 .

There are nearly 1.2 billion adolescents (10–19 years) worldwide, which constitute 18 percent of the world’s population, and in some countries, adolescents make up as much as one-fourth of the population 3 . In India, adolescents comprise more than one-fifth (21.8%) of the total population 4 . Despite a decline projection for the adolescent population in India 5 , there is a critical need to hold adolescents as adolescence is characterized as a period when peer victimization/pressure on psychosocial development is noteworthy 6 . Peer victimization/pressure is further linked to risky sexual behaviours among adolescents 7 , 8 . A higher proportion of low literacy in the Indian population leads to a low level of awareness of HIV/AIDS 9 . Furthermore, the awareness of HIV among adolescents is quite alarming 10 , 11 , 12 .

Unfortunately, there is a shortage of evidence on what predicts awareness of HIV among adolescents. Almost all the research in India is based on beliefs, attitudes, and awareness of HIV among adolescents 2 , 12 . However, few other studies worldwide have examined mass media as a strong predictor of HIV awareness among adolescents 13 . Mass media is an effective channel to increase an individuals’ knowledge about sexual health and improve understanding of facilities related to HIV prevention 14 , 15 . Various studies have outlined other factors associated with the increasing awareness of HIV among adolescents, including; age 16 , 17 , 18 , occupation 18 , education 16 , 17 , 18 , 19 , sex 16 , place of residence 16 , marital status 16 , and household wealth index 16 .

Several community-based studies have examined awareness of HIV among Indian adolescents 2 , 10 , 12 , 20 , 21 , 22 . However, studies investigating awareness of HIV among adolescents in a larger sample size remained elusive to date, courtesy of the unavailability of relevant data. Furthermore, no study in India had ever examined awareness of HIV among adolescents utilizing information on longitudinal data. To the author’s best knowledge, this is the first study in the Indian context with a large sample size that examines awareness of HIV among adolescents and combines information from a longitudinal survey. Therefore, this study intends to examine the change in the awareness level of HIV among adolescents. Furthermore, this study examined the factors associated with a change in awareness level on HIV-related information among adolescents over the period.

Data and methods

Data used for this study were drawn from Understanding the lives of adolescents and young adults (UDAYA), a longitudinal survey on adolescents aged 10–19 in Bihar and Uttar Pradesh 23 . The first wave was conducted in 2015–2016, and the follow-up survey was conducted after three years in 2018–2019 23 . The survey provides the estimates for state and the sample of unmarried boys and girls aged 10–19 and married girls aged 15–19. The study adopted a systematic, multi-stage stratified sampling design to draw sample areas independently for rural and urban areas. 150 primary sampling units (PSUs)—villages in rural areas and census wards in urban areas—were selected in each state, using the 2011 census list of villages and wards as the sampling frame. In each primary sampling unit (PSU), households to be interviewed were selected by systematic sampling. More details about the study design and sampling procedure have been published elsewhere 23 . Written consent was obtained from the respondents in both waves. In wave 1 (2015–2016), 20,594 adolescents were interviewed using the structured questionnaire with a response rate of 92%.

Moreover, in wave 2 (2018–2019), the study interviewed the participants who were successfully interviewed in 2015–2016 and who consented to be re-interviewed 23 . Of the 20,594 eligible for the re-interview, the survey re-interviewed 4567 boys and 12,251 girls (married and unmarried). After excluding the respondents who gave an inconsistent response to age and education at the follow-up survey (3%), the final follow-up sample covered 4428 boys and 11,864 girls with the follow-up rate of 74% for boys and 81% for girls. The effective sample size for the present study was 4421 unmarried adolescent boys aged 10–19 years in wave-1 and wave-2. Additionally, 7587 unmarried adolescent girls aged 10–19 years were interviewed in wave-1 and wave-2 23 . The cases whose follow-up was lost were excluded from the sample to strongly balance the dataset and set it for longitudinal analysis using xtset command in STATA 15. The survey questionnaire is available at https://dataverse.harvard.edu/file.xhtml?fileId=4163718&version=2.0 & https://dataverse.harvard.edu/file.xhtml?fileId=4163720&version=2.0 .

Outcome variable

HIV awareness was the outcome variable for this study, which is dichotomous. The question was asked to the adolescents ‘Have you heard of HIV/AIDS?’ The response was recorded as yes and no.

Exposure variables

The predictors for this study were selected based on previous literature. These were age (10–19 years at wave 1, continuous variable), schooling (continuous), any mass media exposure (no and yes), paid work in the last 12 months (no and yes), internet use (no and yes), wealth index (poorest, poorer, middle, richer, and richest), religion (Hindu and Non-Hindu), caste (Scheduled Caste/Scheduled Tribe, Other Backward Class, and others), place of residence (urban and rural), and states (Uttar Pradesh and Bihar).

Exposure to mass media (how often they read newspapers, listened to the radio, and watched television; responses on the frequencies were: almost every day, at least once a week, at least once a month, rarely or not at all; adolescents were considered to have any exposure to mass media if they had exposure to any of these sources and as having no exposure if they responded with ‘not at all’ for all three sources of media) 24 . Household wealth index based on ownership of selected durable goods and amenities with possible scores ranging from 0 to 57; households were then divided into quintiles, with the first quintile representing households of the poorest wealth status and the fifth quintile representing households with the wealthiest status 25 .

Statistical analysis

Descriptive analysis was done to observe the characteristics of unmarried adolescent boys and girls at wave-1 (2015–2016). In addition, the changes in certain selected variables were observed from wave-1 (2015–2016) to wave-2 (2018–2019), and the significance was tested using t-test and proportion test 26 , 27 . Moreover, random effect regression analysis 28 , 29 was used to estimate the association of change in HIV awareness among unmarried adolescents with household factors and individual factors. The random effect model has a specific benefit for the present paper's analysis: its ability to estimate the effect of any variable that does not vary within clusters, which holds for household variables, e.g., wealth status, which is assumed to be constant for wave-1 and wave-2 30 .

Table 1 represents the socio-economic profile of adolescent boys and girls. The estimates are from the baseline dataset, and it was assumed that none of the household characteristics changed over time among adolescent boys and girls.

Figure  1 represents the change in HIV awareness among adolescent boys and girls. The percentage of adolescent boys who had awareness regarding HIV increased from 38.6% in wave-1 to 59.9% in wave-2. Among adolescent girls, the percentage increased from 30.2% in wave-1 to 39.1% in wave-2.

The percenate of HIV awareness among adolescent boys and girls, wave-1 (2015–2016) and wave-2 (2018–2019).

Table 2 represents the summary statistics for explanatory variables used in the analysis of UDAYA wave-1 and wave-2. The exposure to mass media is almost universal for adolescent boys, while for adolescent girls, it increases to 93% in wave-2 from 89.8% in wave-1. About 35.3% of adolescent boys were engaged in paid work during wave-1, whereas in wave-II, the share dropped to 33.5%, while in the case of adolescent girls, the estimates are almost unchanged. In wave-1, about 27.8% of adolescent boys were using the internet, while in wave-2, there is a steep increase of nearly 46.2%. Similarly, in adolescent girls, the use of the internet increased from 7.6% in wave-1 to 39.3% in wave-2.

Table 3 represents the estimates from random effects for awareness of HIV among adolescent boys and girls. It was found that with the increases in age and years of schooling the HIV awareness increased among adolescent boys ([Coef: 0.05; p  < 0.01] and [Coef: 0.04; p  < 0.01]) and girls ([Coef: 0.03; p  < 0.01] and [Coef: 0.04; p  < 0.01]), respectively. The adolescent boys [Coef: 0.06; p  < 0.05] and girls [Coef: 0.03; p  < 0.05] who had any mass media exposure were more likely to have an awareness of HIV in comparison to those who had no exposure to mass media. Adolescent boys' paid work status was inversely associated with HIV awareness about adolescent boys who did not do paid work [Coef: − 0.01; p  < 0.10]. Use of the internet among adolescent boys [Coef: 0.18; p  < 0.01] and girls [Coef: 0.14; p  < 0.01] was positively associated with HIV awareness in reference to their counterparts.

The awareness regarding HIV increases with the increase in household wealth index among both adolescent boys and girls. The adolescent girls from the non-Hindu household had a lower likelihood to be aware of HIV in reference to adolescent girls from Hindu households [Coef: − 0.09; p  < 0.01]. Adolescent girls from non-SC/ST households had a higher likelihood of being aware of HIV in reference to adolescent girls from other caste households [Coef: 0.04; p  < 0.01]. Adolescent boys [Coef: − 0.03; p  < 0.01] and girls [Coef: − 0.09; p  < 0.01] from a rural place of residence had a lower likelihood to be aware about HIV in reference to those from the urban place of residence. Adolescent boys [Coef: 0.04; p  < 0.01] and girls [Coef: 0.02; p  < 0.01] from Bihar had a higher likelihood to be aware about HIV in reference to those from Uttar Pradesh.

This is the first study of its kind to address awareness of HIV among adolescents utilizing longitudinal data in two indian states. Our study demonstrated that the awareness of HIV has increased over the period; however, it was more prominent among adolescent boys than in adolescent girls. Overall, the knowledge on HIV was relatively low, even during wave-II. Almost three-fifths (59.9%) of the boys and two-fifths (39.1%) of the girls were aware of HIV. The prevalence of awareness on HIV among adolescents in this study was lower than almost all of the community-based studies conducted in India 10 , 11 , 22 . A study conducted in slums in Delhi has found almost similar prevalence (40% compared to 39.1% during wave-II in this study) of awareness of HIV among adolescent girls 31 . The difference in prevalence could be attributed to the difference in methodology, study population, and study area.

The study found that the awareness of HIV among adolescent boys has increased from 38.6 percent in wave-I to 59.9 percent in wave-II; similarly, only 30.2 percent of the girls had an awareness of HIV during wave-I, which had increased to 39.1 percent. Several previous studies corroborated the finding and noticed a higher prevalence of awareness on HIV among adolescent boys than in adolescent girls 16 , 32 , 33 , 34 . However, a study conducted in a different setting noticed a higher awareness among girls than in boys 35 . Also, a study in the Indian context failed to notice any statistical differences in HIV knowledge between boys and girls 18 . Gender seems to be one of the significant determinants of comprehensive knowledge of HIV among adolescents. There is a wide gap in educational attainment among male and female adolescents, which could be attributed to lower awareness of HIV among girls in this study. Higher peer victimization among adolescent boys could be another reason for higher awareness of HIV among them 36 . Also, cultural double standards placed on males and females that encourage males to discuss HIV/AIDS and related sexual matters more openly and discourage or even restrict females from discussing sexual-related issues could be another pertinent factor of higher awareness among male adolescents 33 . Behavioural interventions among girls could be an effective way to improving knowledge HIV related information, as seen in previous study 37 . Furthermore, strengthening school-community accountability for girls' education would augment school retention among girls and deliver HIV awareness to girls 38 .

Similar to other studies 2 , 10 , 17 , 18 , 39 , 40 , 41 , age was another significant determinant observed in this study. Increasing age could be attributed to higher education which could explain better awareness with increasing age. As in other studies 18 , 39 , 41 , 42 , 43 , 44 , 45 , 46 , education was noted as a significant driver of awareness of HIV among adolescents in this study. Higher education might be associated with increased probability of mass media and internet exposure leading to higher awareness of HIV among adolescents. A study noted that school is one of the important factors in raising the awareness of HIV among adolescents, which could be linked to higher awareness among those with higher education 47 , 48 . Also, schooling provides adolescents an opportunity to improve their social capital, leading to increased awareness of HIV.

Following previous studies 18 , 40 , 46 , the current study also outlines a higher awareness among urban adolescents than their rural counterparts. One plausible reason for lower awareness among adolescents in rural areas could be limited access to HIV prevention information 16 . Moreover, rural–urban differences in awareness of HIV could also be due to differences in schooling, exposure to mass media, and wealth 44 , 45 . The household's wealth status was also noted as a significant predictor of awareness of HIV among adolescents. Corroborating with previous findings 16 , 33 , 42 , 49 , this study reported a higher awareness among adolescents from richer households than their counterparts from poor households. This could be because wealthier families can afford mass-media items like televisions and radios for their children, which, in turn, improves awareness of HIV among adolescents 33 .

Exposure to mass media and internet access were also significant predictors of higher awareness of HIV among adolescents. This finding agrees with several previous research, and almost all the research found a positive relationship between mass-media exposure and awareness of HIV among adolescents 10 . Mass media addresses such topics more openly and in a way that could attract adolescents’ attention is the plausible reason for higher awareness of HIV among those having access to mass media and the internet 33 . Improving mass media and internet usage, specifically among rural and uneducated masses, would bring required changes. Integrating sexual education into school curricula would be an important means of imparting awareness on HIV among adolescents; however, this is debatable as to which standard to include the required sexual education in the Indian schooling system. Glick (2009) thinks that the syllabus on sexual education might be included during secondary schooling 44 . Another study in the Indian context confirms the need for sex education for adolescents 50 , 51 .

Limitations and strengths of the study

The study has several limitations. At first, the awareness of HIV was measured with one question only. Given that no study has examined awareness of HIV among adolescents using longitudinal data, this limitation is not a concern. Second, the study findings cannot be generalized to the whole Indian population as the study was conducted in only two states of India. However, the two states selected in this study (Uttar Pradesh and Bihar) constitute almost one-fourth of India’s total population. Thirdly, the estimates were provided separately for boys and girls and could not be presented combined. However, the data is designed to provide estimates separately for girls and boys. The data had information on unmarried boys and girls and married girls; however, data did not collect information on married boys. Fourthly, the study estimates might have been affected by the recall bias. Since HIV is a sensitive topic, the possibility of respondents modifying their responses could not be ruled out. Hawthorne effect, respondents, modifying aspect of their behaviour in response, has a role to play in HIV related study 52 . Despite several limitations, the study has specific strengths too. This is the first study examining awareness of HIV among adolescent boys and girls utilizing longitudinal data. The study was conducted with a large sample size as several previous studies were conducted in a community setting with a minimal sample size 10 , 12 , 18 , 20 , 53 .

The study noted a higher awareness among adolescent boys than in adolescent girls. Specific predictors of high awareness were also noted in the study, including; higher age, higher education, exposure to mass media, internet use, household wealth, and urban residence. Based on the study findings, this study has specific suggestions to improve awareness of HIV among adolescents. There is a need to intensify efforts in ensuring that information regarding HIV should reach vulnerable sub-groups as outlined in this study. It is important to mobilize the available resources to target the less educated and poor adolescents, focusing on rural adolescents. Investment in education will help, but it would be a long-term solution; therefore, public information campaigns could be more useful in the short term.

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This paper was written using data collected as part of Population Council’s UDAYA study, which is funded by the Bill and Melinda Gates Foundation and the David and Lucile Packard Foundation. No additional funds were received for the preparation of the paper.

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Srivastava, S., Chauhan, S., Patel, R. et al. A study of awareness on HIV/AIDS among adolescents: A Longitudinal Study on UDAYA data. Sci Rep 11 , 22841 (2021). https://doi.org/10.1038/s41598-021-02090-9

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Dark blue boxes indicate RRs, and horizontal bars indicate 95% CIs. Sizes of dark blue boxes are proportional to the inverse variance. The light blue diamond indicates the pooled RR estimate and 95% CI in the random-effects model meta-analysis. RRs are maximally adjusted estimates as reported by studies (see eTable 1 in Supplement 1 for adjustment variables). Badr et al 32 for RR of all-cause death and Postigo et al 28 for RR of MACE were crude estimates calculated by this study’s authors based on number of participants and number of events reported for patients living with HIV and control groups. The definition of MACE for Shitole et al 18 and Postigo et al 28 was death or cardiovascular admissions.

RRs are shown for recurrent acute coronary syndrome (ACS) (A), heart failure (HF) admission (B), cardiovascular (CV) death (C), and restenosis (D). Dark blue boxes indicate RRs, and horizontal bars indicate 95% CIs. Sizes of dark blue boxes are proportional to the inverse variance. The light blue diamond indicates the pooled RR estimate and 95% CI in the random-effects model meta-analysis.

eTable 1. Additional Patient Characteristics by Study for Patients Living With HIV and Patients in Control Groups

eTable 2. Comparison of Patient Characteristics Between Patients Living With HIV and Patients in Control Groups

eTable 3. Clinical Outcomes, Relative Risks, and Adjustment Variables by Study

eTable 4. Sensitivity Analysis of Pooled Relative Risks Calculated Using Knapp-Hartung Method for Random-Effects Model Meta-Analysis

eTable 5. Quality Assessment of Included Studies With Newcastle-Ottawa Scale

eFigure 1. Study Flow Sheet

eFigure 2. Pooled Relative Risks for Patients Living With HIV vs Patients in Control Groups for TLR and TVR

eFigure 3. Pooled Unadjusted Relative Risks for Patients Living With HIV vs Patients in Control Groups for All-Cause Mortality, MACE, and Recurrent ACS

eFigure 4. Funnel Plot of Relative Risks for All-Cause Mortality and MACE

eMethods. Detailed Description of Statistical Analysis

Data Sharing Statement

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Haji M , Capilupi M , Kwok M, et al. Clinical Outcomes After Acute Coronary Syndromes or Revascularization Among People Living With HIV : A Systematic Review and Meta-Analysis . JAMA Netw Open. 2024;7(5):e2411159. doi:10.1001/jamanetworkopen.2024.11159

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Clinical Outcomes After Acute Coronary Syndromes or Revascularization Among People Living With HIV : A Systematic Review and Meta-Analysis

• 1 Department of Medicine, Alpert Medical School of Brown University, Providence, Rhode Island
• 2 Department of Medicine, Washington University School of Medicine in St Louis, St Louis, Missouri
• 3 Department of Medicine, Duke Global Health Institute and Duke Clinical Research Institute, Duke University, Durham, North Carolina
• 4 Global Health Institute, University of Washington, Seattle
• 5 Infectious Disease Section, Michael E. DeBakey VA Medical Center, Houston, Texas
• 6 Department of Medicine, Baylor College of Medicine, Houston, Texas
• 7 Pharmacy Service, Michael E. DeBakey VA Medical Center, Houston, Texas
• 8 Center of Innovation, Providence VA Medical Center, Providence, Rhode Island
• 9 Evidence Synthesis Program Center, Providence VA Health Care System, Providence, Rhode Island
• 10 Department of Medicine, Providence VA Medical Center, Providence, Rhode Island
• 11 Department of Pharmacy, University of Rhode Island, Providence
• 12 Department of Health Services, Policy and Practice, Brown University, Providence, Rhode Island

Question   What are the postdischarge outcomes for patients living with HIV after acute coronary syndromes or coronary revascularization?

Findings   In this systematic review and meta-analysis of 15 studies involving 9499 patients living with HIV and 1 531 117 patients without HIV, patients living with HIV had a higher risk of all-cause mortality, major adverse cardiovascular events, recurrent acute coronary syndromes, and admission for heart failure after the index event, despite being approximately 11 years younger at the time of the event. Patients living with HIV were more likely to be current smokers and engage in illicit drug use and had higher triglyceride and lower high-density lipoprotein cholesterol levels than those without HIV.

Meaning   This analysis highlights the need for attention toward secondary prevention strategies to address poor outcomes of cardiovascular disease among patients living with HIV.

Importance   Clinical outcomes after acute coronary syndromes (ACS) or percutaneous coronary interventions (PCIs) in people living with HIV have not been characterized in sufficient detail, and extant data have not been synthesized adequately.

Objective   To better characterize clinical outcomes and postdischarge treatment of patients living with HIV after ACS or PCIs compared with patients in an HIV-negative control group.

Data Sources   Ovid MEDLINE, Embase, and Web of Science were searched for all available longitudinal studies of patients living with HIV after ACS or PCIs from inception until August 2023.

Study Selection   Included studies met the following criteria: patients living with HIV and HIV-negative comparator group included, patients presenting with ACS or undergoing PCI included, and longitudinal follow-up data collected after the initial event.

Data Extraction and Synthesis   Data extraction was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Clinical outcome data were pooled using a random-effects model meta-analysis.

Main Outcome and Measures   The following clinical outcomes were studied: all-cause mortality, major adverse cardiovascular events, cardiovascular death, recurrent ACS, stroke, new heart failure, total lesion revascularization, and total vessel revascularization. The maximally adjusted relative risk (RR) of clinical outcomes on follow-up comparing patients living with HIV with patients in control groups was taken as the main outcome measure.

Results   A total of 15 studies including 9499 patients living with HIV (pooled proportion [range], 76.4% [64.3%-100%] male; pooled mean [range] age, 56.2 [47.0-63.0] years) and 1 531 117 patients without HIV in a control group (pooled proportion [range], 61.7% [59.7%-100%] male; pooled mean [range] age, 67.7 [42.0-69.4] years) were included; both populations were predominantly male, but patients living with HIV were younger by approximately 11 years. Patients living with HIV were also significantly more likely to be current smokers (pooled proportion [range], 59.1% [24.0%-75.0%] smokers vs 42.8% [26.0%-64.1%] smokers) and engage in illicit drug use (pooled proportion [range], 31.2% [2.0%-33.7%] drug use vs 6.8% [0%-11.5%] drug use) and had higher triglyceride (pooled mean [range], 233 [167-268] vs 171 [148-220] mg/dL) and lower high-density lipoprotein-cholesterol (pooled mean [range], 40 [26-43] vs 46 [29-46] mg/dL) levels. Populations with and without HIV were followed up for a pooled mean (range) of 16.2 (3.0-60.8) months and 11.9 (3.0-60.8) months, respectively. On postdischarge follow-up, patients living with HIV had lower prevalence of statin (pooled proportion [range], 53.3% [45.8%-96.1%] vs 59.9% [58.4%-99.0%]) and β-blocker (pooled proportion [range], 54.0% [51.3%-90.0%] vs 60.6% [59.6%-93.6%]) prescriptions compared with those in the control group, but these differences were not statistically significant. There was a significantly increased risk among patients living with HIV vs those without HIV for all-cause mortality (RR, 1.64; 95% CI, 1.32-2.04), major adverse cardiovascular events (RR, 1.11; 95% CI, 1.01-1.22), recurrent ACS (RR, 1.83; 95% CI, 1.12-2.97), and admissions for new heart failure (RR, 3.39; 95% CI, 1.73-6.62).

Conclusions and Relevance   These findings suggest the need for attention toward secondary prevention strategies to address poor outcomes of cardiovascular disease among patients living with HIV.

The widespread use of effective antiretroviral therapies (ARTs) has led to increased survivorship among people living with HIV. Therefore, people living with HIV are experiencing an increased prevalence of age-related disease, such as cardiovascular disease (CVD). 1 , 2 The increase in CVD in this population has been attributed to multiple factors, including increasing age, the increase in burden of traditional CVD factors and psychosocial risk factors, the long-term metabolic effects of ART, and the low-grade immune activation of chronic HIV. 1 , 3 - 8

Epidemiological studies have shown that compared with populations without HIV, people living with HIV have a higher risk of coronary artery disease, acute coronary syndromes (ACS), and heart failure, with onset at younger ages. 4 , 9 - 12 Given this earlier emergence of CVD among people living with HIV, there has been significant attention and evidence generated for primary prevention strategies involving statins. 13 , 14 In conjunction with these studies, characterization of longitudinal CVD outcomes is important to identify strategies for secondary prevention and further improve survivorship among people living with HIV. Studies on clinical outcomes after ACS and percutaneous coronary interventions (PCIs) among patients living with HIV have shown higher rates of recurrent coronary disease and mortality compared with patients in HIV-negative control groups. 11 , 15 - 17 However, this association has not been characterized in sufficient detail in current literature, and extant data have not been adequately synthesized. We conducted a systematic review and meta-analysis of longitudinal studies of patients living with HIV after ACS or PCIs to better characterize clinical outcomes and postdischarge treatment compared with patients in HIV-negative control groups.

We report this systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses ( PRISMA ) reporting guideline. This study was not preregistered. Please see the eMethods in Supplement 1 for a detailed description of methods used in this meta-analysis, as recommended by the International Committee of Medical Journal Editors.

We searched Ovid MEDLINE, Embase, and Web of Science for all available articles from inception to August 2023 for the key terms coronary artery disease , myocardial infarction , non-fatal myocardial infarction , acute coronary syndrome , revascularization , percutaneous coronary intervention , and secondary prevention . We also reviewed references of relevant articles.

Articles were screened by 2 reviewers (M.H. and M.C.) by title and abstract and later by full text. We included studies if they fulfilled the following criteria: patients living with HIV and a comparator group of patients without HIV (control group) included, patients with obstructive coronary artery disease presenting with ACS or undergoing revascularization through PCI included, and longitudinal follow-up data on clinical outcomes after initial event collected. We initially also searched for studies that discussed outcomes after stroke and peripheral artery disease.

We extracted the following data where available using standardized forms: study characteristics, baseline demographics (ie, age, sex, and race and ethnicity) and other characteristics (ie, underlying comorbidities, revascularization strategies, and postdischarge medications) of HIV-positive and HIV-negative control populations, HIV-specific characteristics (use of ART, CD4 count, and viral load), number of events by group and hazard ratios (HRs) of clinical outcomes (ie, all-cause mortality, major adverse cardiovascular events [MACE], cardiovascular death, recurrent ACS, stroke, total lesion revascularization, total vessel revascularization, and admission for heart failure). We extracted maximally adjusted HRs where available, as well as unadjusted (crude) or minimally adjusted HRs for clinical outcomes. We captured data on race and ethnicity to help assess the full scope of diversity among patients living with HIV and how applicable our data may be within the global population of people living with HIV. Race and ethnicity were self-reported in the study by Shitole et al. 18 In the other studies reporting this information, data were obtained from review of medical records, including electronic health records. Reported race and ethnicity categories included African American, American Indian, Asian, Hispanic, Pacific Islander, White, and other. We primarily report aggregated data for Black, White, and Hispanic populations only given that there were limited data available on other races and ethnicities.

We combined summary study characteristics (eg, mean age, percentage male and female, percentage Black and White, and percentage Hispanic) across studies using study sizes as analytical weights to provide estimates of pooled means or percentages. The δ and P values comparing summary study-level characteristics (means or prevalences pooled across studies) between HIV-positive and HIV-negative groups were calculated from a linear regression model of each variable on HIV status weighted by the number of participants for each study (ie, a fixed-effects meta-regression). When HRs were not reported, we calculated crude risk ratios from the number of events in each group. In 2 studies, 15 , 19 data were reported as odds ratios. We pooled HRs of clinical outcomes across studies using a random-effects model meta-analysis, estimating between-study heterogeneity using the DerSimonian-Laird method. 20 As a sensitivity analysis, we also estimated between-study heterogeneity using the residual maximum likelihood method and calculated variances ( P values and CIs) of pooled relative risk (RR) estimates using modifications proposed by Knapp and Hartung. 21 For the purpose of the meta-analysis, we considered odds ratios, risk ratios, and HRs as equivalent measures of RR.

We assessed between-study heterogeneity using the Cochran Q statistic and I 2 statistic, which estimates the percentage of total variation across studies due to true between-study difference rather than chance. 22 , 23 We did not explore heterogeneity further owing to the limited numbers of studies available for most comparisons.

The quality of included studies was assessed using the Newcastle-Ottawa Scale for cohort studies. 24 We visually inspected funnel plots to assess the risk of publication bias. We also performed the Egger test for small study bias, although this was limited by the small number of studies that were generally available for investigated outcomes. Where there were P values trending toward small study bias, we performed trim and fill analyses to help assess the impact of the bias on pooled estimates (even if Egger test P values did not reach statistical significance). A 2-sided P value less than .05 was considered statistically significant. For the meta-analysis of RRs, we report point estimates and 95% CIs. All analyses were performed using Stata software statistical software version 15 (StataCorp).

An initial search yielded 3263 studies, which were screened using titles, abstracts, and full texts. Studies reviewing patient outcomes after diagnoses and interventions of peripheral artery disease and stroke were limited, reporting mainly in-hospital outcomes, short-term follow-up, or results without non-HIV comparator groups, and were not further considered in this meta-analysis. We identified 15 studies 11 , 15 , 16 , 18 , 25 - 35 of post-ACS or revascularization outcomes from 2003 to 2023 that met inclusion criteria (eFigure 1 in Supplement 1 ). Of identified studies, 2 were abstracts. 30 , 31 All were retrospective cohort studies except for 3 prospective studies ( Table 1 ). 11 , 26 , 30

Details of patient characteristics and outcomes by study are presented in Table 1 and eTable 1 in Supplement 1 . A total of 9499 patients living with HIV (pooled proportion [range], 76.4% [64.3%-100%] male; pooled mean [range] age, 56.2 [47.0-63.0] years; pooled proportion [range], 10.1% [95% CI, 7.0%-62.5%] Black; 8.1% [95% CI, 0.4%-54.6%] Hispanic, and 13.1% [95% CI, 7.2%-64.0%] White) and 1 531 117 patients in control groups without HIV (pooled proportion [range], 61.7% [59.7%-100%] male; pooled mean [range] age, 67.7 [42.0-69.4] years; pooled proportion [range], 3.3% [95% CI, 2.5%-21.4%] Black, 3.6% [95% CI, 0.7%-36.3%] Hispanic, and 21.1% [95% CI, 14.3%-68.0%] White) who experienced ACS or underwent coronary revascularization were included in the meta-analysis. Summary baseline characteristics of study participants and comparisons of patients living with HIV with patients in control groups are presented in Table 2 and eTable 2 in Supplement 1 . The mean age of patients living with HIV was 11.1 years (95% CI, 6.2-16.0 years) less than that of patients in HIV-negative control groups ( P  < .001). HIV-positive and control populations were similarly male dominant. Patients living with HIV were statistically significantly more likely to be current smokers (pooled proportion [range], 59.1% [24.0%-75.0%] smokers vs 42.8% [26.0%-64.1%] smokers; P  < .001) and engage in illicit drug use (pooled proportion [range], 31.2% [2.0%-33.7%] drug use vs 6.8% [0%-11.5%] drug use; P  < .001) and had significantly higher pooled mean (range) triglyceride (233 [167-268] vs 171 [148-220] mg/dL; P  = .01) and lower pooled mean (range) high-density lipoprotein cholesterol (40 [26-43] vs 46 [29-46] mg/dL; P  = .03) levels. (To convert triglycerides and cholesterol to millimoles per liter, multiply by 0.0113 and 0.0259, respectively.) There were similar proportions of patients with diabetes, hypertension, and a family history of coronary artery disease in the 2 groups ( Table 2 ; eTable 2 in Supplement 1 ).

Patients with HIV had been diagnosed with HIV for a pooled mean (range) of 11.2 (8.5-12.0) years. From 9 studies 11 , 16 , 18 , 26 , 28 , 29 , 31 , 34 , 35 that provided these data, a pooled proportion (range) of 75.2% (50.0%-94.1%) of patients living with HIV were receiving ART and 47.6% (25.0%-85.6%) had previously received protease inhibitor therapy. The pooled mean (range) CD4 count was 377 (318-462) cells/mm 3 among patients living with HIV, and most of these patients (pooled proportion [range], 77.8% [63.3%-94.6%]) had a viral load less of than 200 copies per mL ( Table 2 ).

Among 13 studies 11 , 15 , 16 , 18 , 25 - 29 , 31 - 34 that reported data on ACS, patients living with HIV and those in control groups presented similarly with ST-segment elevation myocardial infarction, non–ST-segment elevation myocardial infarction, and unstable angina. Additionally, the groups received PCIs or coronary artery bypass graft surgery at similar proportions. After revascularization, pooled mean (range) left ventricular ejection fraction values were similar between groups (49.4% [44.0%-55.4%] vs 50.9% [48.0%-54.8%]). On postdischarge follow up, patients living with HIV had a lower proportion (range) of statin (53.3% [45.8%-96.1%] vs 59.9% [58.4%-99.0%]) and β-blocker (54.0% [51.3%-90.0%] vs 60.6% [59.6%-93.6%]) prescription compared with patients in control groups, but these differences were not statistically significant ( Table 2 ; eTable 2 in Supplement 1 ).

Over a pooled mean (range) follow-up of a mean of 16.2 (3.0-60.8) months after ACS or revascularization, patients living with HIV had a significantly higher adjusted risk of all-cause mortality (pooled adjusted RR, 1.64; 95% CI, 1.32-2.04), MACE (RR, 1.11; 95% CI, 1.01-1.22), recurrent ACS (RR, 1.83; 95% CI, 1.12-2.97), and heart failure readmission (RR, 3.39; 95% CI, 1.73-6.62) ( Figure 1 ), as well as restenosis (RR, 2.40; 95% CI, 1.13-5.09) ( Figure 2 ) compared with patients in HIV-negative control groups (pooled mean [range] follow-up, 11.9 [3.0-60.8] months). For CV death, total vessel revascularization, and total lesion revascularization, pooled HRs showed no significantly higher risk among patients living with HIV compared with patients in control groups (eFigure 2 in Supplement 1 ). RRs of clinical outcomes and adjustment variables included in multivariate models that were reported by each study are presented in eTable 3 in Supplement 1 . Sensitivity analyses specifying an alternative method for the random-effects model yielded comparable results (eTable 4 in Supplement 1 ). In a separate subsidiary analysis, there was no association between HIV status and risk of post–ACS or PCI mortality, recurrent ACS, or MACE outcomes in the unadjusted (minimally adjusted in some studies) model (eFigure 3 in Supplement 1 ).

There was generally low heterogeneity across studies for most outcomes ( Figure 1 and Figure 2 ). Visual inspection of the funnel plot for publication bias assessment and Egger tests did not suggest the presence of significant publication bias (eFigure 4 in Supplement 1 ). For the all-cause mortality outcome, the Egger test for bias was borderline, and so we performed trim and fill analysis; this yielded similar results (RR, 1.61; 95% CI, 1.30-2.00). Included studies were of moderate to high quality based on the Newcastle-Ottawa Scale, indicating a low to moderate risk of bias (eTable 5 in Supplement 1 ).

We performed a literature-based systematic review and meta-analysis of 15 studies of longitudinal clinical outcomes after ACS or revascularization from 2003 to 2023, comprising a total of 9499 patients living with HIV and 1 531 117 patients without HIV in control groups. We found that patients living with HIV were younger and had a higher risk of all-cause mortality, MACE, recurrent ACS, and heart failure after the index event. We also noted lower rates of statin and β-blocker prescription after discharge among patients living with HIV. Overall, these findings highlight the need to develop and implement strategies for secondary prevention of CVD among patients living with HIV.

The increased mortality, recurrence of ACS, and heart failure admissions among patients living with HIV may be attributed to increased traditional CVD risk factors, psychosocial factors, HIV-related chronic inflammation, and long-term effects of ART. 11 , 16 These factors are equally difficult to control after an initial coronary event. 19 , 35 , 36 The study by Boccara et al 11 from 2020 compared its findings with those of their first, 2011 study 37 and noted an increased rate of recurrence of ACS in patients living with HIV; the authors also noted persistent smoking and chronic inflammation as factors associated with some of the greatest increases in risk for recurrent disease. This further reinforces the need for a multifaceted approach to secondary prevention.

Of note, our study found suboptimal statin prescription in patients living with HIV after ACS or revascularization, which is consistent with results of other retrospective studies. 11 , 18 , 19 , 26 , 28 , 38 - 42 These findings and those of the Evaluating the Use of Pitavastatin to Reduce the Risk of Cardiovascular Disease in HIV-Infected Adults (REPRIEVE) trial, 14 which demonstrated the benefits of pitavastatin for primary prevention of atherosclerotic cardiovascular disease among patients living with HIV, highlight the need for a concerted effort to improve guideline-directed statin prescription and adherence among these patients. 43 Additionally, the higher prevalence of smoking and higher triglyceride levels we found among patients living with HIV highlight areas for optimization, with the goal of improving secondary prevention of atherosclerotic cardiovascular disease. Differences in statin and β-blocker prescriptions on follow-up were not statistically significant, although patients living with HIV had numerically lower percentages for both outcomes.

Our pooled estimates for postdischarge antiplatelet therapy are influenced by the study from Parks et al, 33 which defined antiplatelet use as a filled prescription for clopidogrel, ticagrelor, prasugrel, or ticlopidine and as a retrospective observational study, could not reliably exclude patients with type 2 myocardial infarctions who would not typically qualify for these therapies. In that study’s sensitivity analyses of patients who received coronary angiography, percentages of patients with postdischarge antiplatelet therapies were significantly higher. We performed an analysis of aggregate postdischarge antiplatelet therapy rates excluding data from Parks et al, 33 and aggregate data for postdischarge antiplatelet therapy was much higher.

Few studies reported race or ethnicity of participants, leading to overall low aggregate percentages of White and Black patients living with HIV in our analysis, which is not representative of the global population of these patients. Race and ethnicity in most studies were obtained from review of electronic health records, except in the study by Shitole et al, 18 in which race and ethnicity were self-reported. The analysis of race and ethnicity was skewed by 2 studies; in 1 study, 44 most of the population’s race and ethnicity was unknown, and in the other study, 19 the population was mainly Hispanic. Likewise, the percentage of patients who underwent PCIs was lower than expected for a typical population presenting with ACS. This was also contributed by the Parks et al study, 33 which included patients with type 2 myocardial infarctions, who were not candidates for PCIs in their analysis.

Most studies in our analysis included patients receiving ART with low viral loads and CD4 counts greater than 200 cells/mm 3 , indicating patients with good control of their HIV disease, who are representative of people living with HIV in the current era. 1 , 4 , 7 , 45 We found 8 studies 11 , 16 , 26 - 28 , 31 , 34 , 35 that reported use of protease inhibitors among approximately 50% of patients living with HIV (47.6%). Protease inhibitors are known to have metabolic effects associated with CVD, presenting a plausible explanation for the difference in hypertriglyceridemia between patients living with HIV and patients without HIV in our study. 46 Modern ART regimens have transitioned away from the use of protease inhibitors and now include integrase inhibitors. 7 Conflicting data have emerged around the possible association of integrase inhibitors with increased incidence of CVD. 47 , 48 Therefore, further research on long-term outcomes associated with ART will be essential to primary and secondary prevention of CVD among patients living with HIV.

The period after ACS or PCI provides additional opportunity to introduce aggressive interventions to improve CVD risk factors in patients living with HIV, and these interventions may involve multidisciplinary teams. Ensuring access to and engagement of cardiologists for patients living with HIV will be important to improve outcomes, especially among underrepresented racial and ethnic minorities. 49 Input from pharmacists can also help with optimal selection of statin types, other lipid-lowering agents, and dosages to avoid drug interactions and drug-related adverse effects and maximize adherence to these therapies. Additionally, input from addiction medicine specialists and psychologists can help address underlying mental health disorders (eg, depression and anxiety) and behavioral risk factors (eg, smoking, alcohol use, and cocaine use). In our study, patients living with HIV were more likely to be smokers and engage in illicit drug use, similar to contemporary studies that also show that these behaviors are associated with an overall increased mortality in patients living with HIV despite adequate control of their underlying infection. 50 Likewise, assistance from social workers can help to mitigate social determinants associated with diet and the ability to afford crucial medications. 36 , 51 - 53 Addressing this latter aspect is critically important to improve secondary outcomes of CVD in patients living with HIV because despite increased prescription rates for cardioprotective medications, patients living with HIV have been found to be less likely to fill these medications. 38 , 42 , 52 A multifaceted or multidisciplinary intervention to address psychosocial barriers to cardiovascular care may have the potential to limit mortality and morbidity after ACS or PCI for patients living with HIV.

The findings of this meta-analysis should be considered in context of several limitations. First, given that this was a literature based meta-analysis of aggregate published data, we were unable to compare the association between HIV status and CVD outcomes by clinically important subgroup, such as age, race and ethnicity, or sex. Second, the degree of adjustment for confounders in RR estimates is limited to what is reported in individual studies, is not consistent across studies, and may be inadequate overall. For instance, very few studies accounted for HIV-specific characteristics. However, the goal of the meta-analysis was to understand the difference in secondary CVD outcomes stratified by HIV status regardless of factors that may be contributing to them. We also performed a comparison between maximally adjusted and unadjusted or minimally adjusted RRs to provide further insight into the association. Our analysis showed that there was no association between HIV status and post-ACS or -PCI mortality, recurrent ACS, or MACE outcomes in the unadjusted model. This is likely due to the reverse confounding effect of age given that patients living with HIV were significantly younger than patients in control groups, with a difference of 11 years in pooled mean age across studies. Third, most studies included in this review evaluated patients living with HIV who lived in high-income countries, which may limit generalizability to the global population of patients living with HIV. Fourth, we were not able to perform subgroup analyses of patients who had ACS and were treated medically vs PCI, as well as those who received PCI for stable coronary disease, because these data were not reported separately. Future assessment of outcomes within these subgroups would be important for preventative efforts. Fifth, we were unable to identify timelines for prescription of or adherence to ART or cardioprotective medications based on these aggregate data. Understanding these trends will also be an important focus for secondary prevention in future studies.

In this literature based systematic review and meta-analysis of longitudinal studies from 2000 to 2023, we found that patients living with HIV were significantly younger than patients in control groups. Patients living with HIV had a significantly higher risk of all-cause mortality, MACE, recurrent ACS, and admission for heart failure after the index event compared with patients in control groups.

Patients living with HIV were also significantly more likely to be current smokers and engage in illicit drug use and had higher triglyceride levels at baseline. As more data emerge for primary prevention, this analysis highlights the need for optimization of secondary prevention strategies to address poor outcomes of CVD among patients living with HIV. Future studies can focus on assessing the role of aggressive interventions, including use of multidisciplinary teams to target important risk factors and improve prescription of and adherence to cardioprotective medications among patients living with HIV after ACS or PCI.

Accepted for Publication: March 7, 2024.

Published: May 14, 2024. doi:10.1001/jamanetworkopen.2024.11159

Open Access: This is an open access article distributed under the terms of the CC-BY License . © 2024 Haji M et al. JAMA Network Open .

Corresponding Author: Sebhat Erqou, MD, PhD, Department of Medicine, Providence VA Medical Center, 830 Chalkstone Ave, Providence, RI 02908 ( [email protected] ).

Author Contributions: Drs Haji and Erqou had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Haji, Ashong, Richard, Wu, Erqou.

Acquisition, analysis, or interpretation of data: Haji, Capilupi, Kwok, Ibrahim, Bloomfield, Longenecker, Rodriguez-Barradas, Jutkowitz, Taveira, Sullivan, Rudolph, Wu, Erqou.

Drafting of the manuscript: Haji, Capilupi, Kwok, Taveira, Erqou.

Critical review of the manuscript for important intellectual content: Capilupi, Kwok, Ibrahim, Bloomfield, Longenecker, Rodriguez-Barradas, Ashong, Jutkowitz, Taveira, Richard, Sullivan, Rudolph, Wu.

Statistical analysis: Kwok, Erqou.

Obtained funding: Erqou.

Administrative, technical, or material support: Haji, Capilupi, Kwok, Jutkowitz, Sullivan, Rudolph, Wu.

Supervision: Bloomfield, Taveira, Richard, Rudolph, Wu, Erqou.

Conflict of Interest Disclosures: Dr Longenecker reported receiving personal fees from Theratechnologies advisory board outside the submitted work. Dr Jutkowitz reported receiving grants from the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development during the conduct of the study. Dr Rudolph reported receiving grants from the National Institute on Aging during the conduct of the study. No other disclosures were reported.

Funding/Support: This study was supported by a VISN 1 Career Development Award from the Department of Veterans Affairs, Veterans Health Administration, to Dr Erqou. Dr Erqou was also funded by the Center for Aids Research, Rhode Island Foundation, and Lifespan Cardiovascular Institute. Drs Sullivan, Rudolph, and Wu were funded by grants CIN 13-419 and C19-20-213 from the VA Health Services Research and Development Center of Innovation in Long Term Services and Supports.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the US government.

Data Sharing Statement: See Supplement 2 .

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• Published: 16 May 2024

Magnitude of intestinal parasitic infections and its determinants among HIV/AIDS patients attending at antiretroviral treatment centers in East and West Gojam Zones, Northwest, Ethiopia: institution based cross-sectional study

• Mengistu Endalamaw 1 ,
• Abel Alemneh 1 ,
• Gashaw Azanaw Amare 1 ,
• Abebe Fenta 1 &
• Habtamu Belew 1  

AIDS Research and Therapy volume  21 , Article number:  32 ( 2024 ) Cite this article

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Intestinal parasitic infections (IP) are a major source of morbidity in people living with Human immunodeficiency virus (HIV), particularly in resource-limited settings, mostly as a result of high viral load. Hence, this study aimed to investigate the magnitude of intestinal parasitic infections and its determinants among patients with HIV/AIDS attending public health facilities in East and West Gojam Zones in Ethiopia.

Institution-based cross-sectional study was conducted on 327 people living with HIV visiting public health facilities from December 2022 to May 2023. A simple random sampling technique was used to recruit participants. Face-to-face interviews were used to collect socio-demographics and determinants. The fresh stool was collected from each patient, transported, and tested in accordance with laboratory standard operating procedures of wet mount, formol-ether concentration technique, and modified acid-fast staining. Data were entered and analyzed in the statistical package for Social Science (SPSS) version 20. A 95% CI with p-value < 0.05 was considered statistically significant.

The overall prevalence of IP in patients with HIV/AIDS was 19.3% (63/327). Hookworm was the most identified parasite 33.3% (21/63) followed by E.histolytica 17% (11/63) and G. lamblia 14.3% (9/63). Parasitic infections were significantly higher among viral load > 1000cps/ml ( p  = 0.035), WHO stage 4 ( p  = 0.002), CD4 < 200 cell/mm 3 ( p  = 0.001), and bare foot walking ( p  = 0.001).

IP infections are moderately high among patients with HIV/AIDS in the study area. The proportion of parasites was greatly affected by high viral load, WHO stage 4, CD4 < 200 cell/mm 3 , and being barefoot; this gives valuable insight to health professionals, health planners and community health workers. As a result, viral load monitoring, and WHO stage controlling were periodically assessed in patients with HIV/AIDS. Health education, awareness creation, routine stool examination, and environmental hygiene were regularly advocated to increase the life of patients with HIV/AIDS.

Introduction

Human immune deficiency virus HIV) is the most fatal virus causing the disease called acquired immunodeficiency syndrome (AIDS), this disease is known to depress the immune system of the infected individual, which favors other infectious organisms to cause disease including IP infections ( 1 ). Parasitic infections are the frequent cause of morbidity and mortality associated with AIDS patients by causing diarrhea, Cryptosporidium parvum and Isospora belli  are the most common opportunistic infectious parasites ( 2 ). In Ethiopia, HIV/AIDS remains a significant public health concern, with a high prevalence and substantial impact on the population ( 3 ). In Ethiopia, the total number of people with HIV/AIDS is 617,921, comprising 235,550 males and 382,371 females across all age groups, with 40, 528 children ( 4 ). Despite progress in the prevention and treatment of HIV/AIDS, co-infections with intestinal parasites continue to pose a significant public burden on affected individuals ( 5 ). Ongoing replication of HIV leads to a constant state of immune activation that persists during the chronic phase. This immune activation is characterized by heightened activity of immune cells and the release of proinflammatory cytokines. It occurs due to the effects of various HIV gene products as well as the immune response triggered by continuous HIV replication. Furthermore, the depletion of mucosal CD4 + T cells in the early stage of the disease disrupts the immune surveillance system of the intestinal barrier, contributing to immune activation ( 6 , 7 ). Intestinal parasite infections have been shown to exacerbate the immunosuppression associated with HIV/AIDS, resulting in increasing susceptibility of opportunistic infections leading to decreased life expectancy rates among people living with HIV/ADIS ( 8 ).

The burden of IP among HIV patients in Africa was found to be more prevalent from 20.9% to 65.3% ( 9 , 10 , 11 , 12 , 13 ), and in Ethiopia, the magnitude of IP in people with HIV from 2011 to 2020 was 39.15% ( 14 ). The East and West Gojam Zones, located in the Northwest region of Ethiopia, are known for the high prevalence of HIV/AIDS ( 15 ). However, limited research has been conducted to assess the magnitude of intestinal parasite infections among patients with HIV in East and West Gojam Zones. Understanding the prevalence and associated factors of intestinal parasite infections in this vulnerable population is crucial for developing targeted interventions and improving the overall health outcomes of patients with HIV ( 5 ).

This research aims to determine the magnitude of intestinal parasite infections and their associated factors among patients with HIV attending antiretroviral therapy in the East and West Gojam Zones of Northwest Ethiopia. By assessing the prevalence of intestinal parasite infections and identifying the factors contributing to their occurrence, this study seeks to provide valuable insights for policymakers, healthcare providers, and researchers working toward the control and prevention of these infections.

Study area and study design

A cross-sectional study was conducted from December 2022 to May 2023 at selected public health institutions from East and West Gojam zones in North-western Ethiopia. Debre Markos Comprehensive Specialized Hospital (DMCSH) provides service for 1340, Yejube Primary Hospital (YPH) 385 and Lumamie Primary Hospital (LPH) 221 from the East Gojam zone, and Finote Selam General Hospital (FSGH) 620 from the West Gojam.

Study population

All HIV-positive patients who attended ART clinics at selected public health facilities.

Exclusion criteria

People living with HIV/AIDS who had a mental illness, because they were unable to provide consent and patients who received anti-parasitic drugs within two weeks were excluded.

Sample size determination

The sample size was determined by using the single population proportion formula, with the formula n = (Z a/2 ) 2 *P (1-P)/d 2 , where n is the minimum required sample size, P is the prevalence of intestinal parasite among HIV patients from a previous study ( p  = 24.2%) ( 16 ), d is the marginal error between the sample and the population ( d  = 0.05), and Z is the critical value at 95% certainty (1.96). Then n  = (1.96) 2 (0.242) (0.799)/(0.05) 2  = 297.

The final sample size, including a 10% non-responding rate, was 327.

Sampling technique and sampling procedure

A simple random sampling with a computer-generated technique was used to select study participants in each selected health institution and proportionally allocated in each facility. From DMCSH ( n  = 171), FSGH ( n  = 79), LPH ( n  = 49), and YPH ( n  = 28) were collected.

Data collection, processing, and analysis

Data collection.

Socio-demographic and clinical data were collected through a face-to-face interviewer-administered structured questionnaire.

Stool sample collection

A fresh stool sample was collected with clean and wide-mouthed plastic containers and was preserved by formalin for the direct wet mount, formal-ether concentration, and modified acid-fast staining, if not processed immediately.

Stool sample direct microscopy

A fresh stool sample was collected in labeled cups from all study participants and a direct saline wet mount of each sample was done at the laboratory for motile trophozoite, ova, cyst, and larval stages of intestinal parasites. The wet mounts were examined under the light microscope at 10X and 40X objectives.

Formol-Ether concentration technique

The formol-ether sedimentation technique was performed from fresh and preserved stool samples as follows. A suspension of stool was made from a gram of stool sample with 7 ml of formalin in a 15 ml conical centrifuge tube and filtered through the sieve, then 3 ml of diethyl ether was added into and centrifuged at 3200 rpm for 3 min. After that, the smear was made from the sediment for microscopic examination under 10 × and 40 × objectives.

Modified Ziehl Neelson method

A small portion of the fresh stool sample was processed for the detection of opportunistic parasites using the modified Ziehl-Neelson method. A thin smear was prepared directly from the sediment of concentrated stool and allowed to air dry. Then the slide was fixed with methanol for 5 min and it was stained with 1% carbol-fuchsine for 30 min. After washing the slide in tap water, the slide was decolorized with 1% acid alcohol for 2 min and stained in 0.5% methylene blue for 1 min. The slide was then washed in tap water and observed under a light microscope with a magnification of 1000X.

Data analysis

Data was entered and analyzed by using the SPSS version 20 software package. Univariate and multivariate logistic regression were used to assess the associations of independent variables and dependent variables. All variables with p-values less than 0.25 in the Univariate analysis were candidates for multivariable logistic regression analysis to resolve the confounding effects. The association between independent variables and dependent variables was considered to be statistically significant only if the P value was less than < 0.05 at a 95% confidence level.

Socio-demographic characteristics of the study population

A total of 327 individuals living with HIV/AIDS were enrolled in the study. Most of the participants, 52% ( n  = 170) were urban residents. The majority (54.2%) of the study participant’s age group was from 21 to 40 years and 63% were married. Regarding the educational status of the study participants, 38.2% were illiterate and 31.8% had high school (Table  1 ).

Prevalence and distribution of intestinal parasites

The overall prevalence of IP among people living with HIV/AIDS was 19.3% ( n  = 63). Of which 33.3% ( n  = 21) were Hookworm , which was the highest prevalent followed by 17% ( n  = 11) E. histolytica . Distribution of helminthic parasites 58.7% ( n  = 37) were more prevalent than protozoan parasites 41.3% ( n  = 26) (Fig.  1 ).

Intesting parasite distribution among people living with HIV/AIDS in West and East Gojam, Ethiopia, 2023

Association of intestinal parasites with socio-demographic and other risk factors

Out of the total 63 IP-positive participants, 69.8% ( n  = 44) were female, and 30.2% ( n  = 19) were male. The majority, 28.6% of infected individuals were aged 31–40, and individuals aged 51–60 had less probability of being infected with IP (6.3%), regarding the marriage status the majority of infected participants 71.4% ( n  = 45) were married. Of patients with HIV diagnosed with IP infection, 58.7% (n = 37) had latrines, and 45.9% (n = 17) of participants used them always, whereas 35.2% (n = 13) didn’t use them at all. Of co-infected 98.4% had regular hand-washing habits before meals (Table  2 ).

Multivariate analysis was done to determine the further association of the potential confounding factors such as sex, age, educational status, marital status, income, presence of latrine, viral load, and World Health Organization (WHO) stage with intestinal parasitosis. As a result, viral load level, WHO stage 4 of HIV/AIDS (the severely symptomatic stage) ( 17 ), and availability of latrine showed significant association. People living with HIV who had viral load count 20–1000 cps/ml were more likely to develop a parasitic infection than those having a viral load count results of target not detected (TND) (AOR = 2.37, 95% CI 1.92, 20.1) and those who did not have latrine were 1.2 times more likely acquire intestinal parasite infection than those who had latrine (AOR = 1.21, 95% CI 1.1, 3.4). Patients who had WHO stage 4 of HIV/AIDS were more likely infected with parasitic infection than those who had stage 1. (AOR = 3.83, 95% CI 1.23, 11.54) (Table  2 ).

The present study investigated the socio-demographic characteristics and prevalence of IPs among individuals living with HIV/AIDS in East and West Gojam Zones, Amhara region, Ethiopia. The findings of this study provide important insights into the factors associated with IP infections in this specific geographic area.

The socio-demographic characteristics of the study population revealed that most participants were urban residents (52%), aged between 21 and 40 (54.2%), and 38.2% couldn’t read and write, while 31.8% had completed high school. This finding is consistent with previous reports in different parts of Ethiopia. The higher rates of HIV/AIDS in urban areas due to factors such as increased mobility, higher population density, and greater access to healthcare services, and the global HIV/AIDS epidemiology reported that young adults are often at higher risk of HIV infection due to behavioral factors, including engaging in risky sexual behaviors and substance abuse. Low educational attainment is often associated with limited health literacy, which can hinder individuals' ability to understand and adopt preventive measures against parasitic infections ( 18 , 19 , 20 , 21 , 22 , 23 ).

The overall prevalence of IPs among people living with HIV/AIDS attending the study areas was 19.3%. This finding is consistent with some previous studies conducted in Amhara region, Ethiopia, which have reported a high burden of IP infections among HIV-positive individuals ( 19 , 24 ). However, our finding was much lower than the expected prevalence obtained from the systematic review and meta-analysis research in Ethiopia (39.15%) ( 14 ). This might be due to in the study area people living with HIV/AIDS have a strong adherence to ART drugs, counseling, improved knowledge through health education, and good sanitation practices. The prevalence of specific parasites in this study revealed that hookworms were the most prevalent (33.3%), followed by E. histolytica (17%). These findings are consistent with the literature, as hookworm infection is known to be highly prevalent in Ethiopia, particularly in rural areas with poor sanitation and hygiene practices ( 25 ).

The association analysis between intestinal parasitosis and socio-demographic and other risk factors revealed several important findings. Female participants had a higher likelihood of being infected with intestinal parasites compared to males. This finding is consistent with previous studies in Ethiopia, which have reported a higher prevalence of intestinal parasites among females living with HIV/AIDS ( 26 ). This might be due to biological factors like immunosuppression and gastrointestinal changes, socially limited access to healthcare, stigma, and discrimination associated with HIV/AIDS, poor nutritional status, and cultural like menstrual hygiene practices and traditional practices (herbal medicine usage) differences in hygiene practices, may contribute to this gender disparity. The presence of a latrine/toilet was found to be a significant protective factor against intestinal parasitic infections. Participants who did not have access to a latrine were 1.2 times more likely to acquire such infections compared to those who had access. This finding highlights the importance of proper sanitation and hygiene practices in preventing parasitic infections, particularly in resource-limited settings like East and West Gojam Zones. Lack of access to adequate sanitation facilities increases the risk of fecal–oral transmission of parasites ( 27 , 28 ).

Furthermore, the viral load level and the WHO stage of HIV/AIDS were significantly associated with intestinal parasitosis. Individuals with a viral load count between 20 and 1000 cps/ml were more likely to develop parasitic infections compared to those with undetectable viral load counts. This finding suggests that individuals with higher viral loads may have compromised immune systems, making them more susceptible to opportunistic infections, including intestinal parasites ( 23 , 29 ). Additionally, patients in WHO stage 4 of HIV/AIDS had a higher likelihood of being infected with parasitic infections compared to those in stage 1. Advanced HIV/AIDS disease progression weakens the immune system, increasing vulnerability to various infections, including parasitic infections ( 30 ).

Individuals with a CD4 count below 200 cell/mm 3 , indicating advanced HIV/AIDS progression, had a significantly higher likelihood of being infected with intestinal parasites. In this study, the adjusted odds ratio was 5.7 (95% CI 2.77–11.7). Even individuals with a CD4 count between 200 and 500 cells/mm 3 showed an increased risk of parasitic infections compared to those with higher CD4 counts, with an adjusted odds ratio of 4.6 (95% CI 1.80–11.7, p-value = 0.001). Walking barefoot was also significantly associated with a higher risk of parasitic infections, with an adjusted odds ratio of 6.6 (95% CI 2.7–16.4, p-value = 0.001). These findings emphasize the importance of monitoring CD4 counts, promoting preventive measures, and improving hygiene practices, including the use of footwear, to reduce the burden of intestinal parasitic infections among individuals living with HIV/AIDS.

The findings of this study have important implications for public health interventions in East and West Gojam Zones, Amhara region, Ethiopia. Targeted interventions should focus on improving health literacy and promoting proper sanitation and hygiene practices among individuals living with HIV/AIDS. Efforts to increase awareness about the importance of regular screening and appropriate treatment for intestinal parasitic infections are crucial. Integration of interventions targeting both HIV/AIDS and parasitic infections is recommended to improve the overall health outcomes of individuals living with HIV/AIDS. This can include providing comprehensive healthcare services that address both HIV/AIDS management and the prevention and treatment of parasitic infections. The strength of this study was used different parasitological diagnostic modalities to detect IPs in people living with HIV/AIDS, however, there was a delayance in sample transportation to the reference laboratory which performed formol-ether concentration technique and modified acid-fast staining, this issue could affect the prevalence of IPs among the participants.

This study highlights the high prevalence of intestinal parasitic infections among individuals living with HIV/AIDS in East and West Gojam Zones, Amhara region, Ethiopia. The findings underscore the importance of addressing socio-demographic factors, such as gender and educational status, as well as improving sanitation and hygiene practices among this vulnerable population. Integrated interventions that target both HIV/AIDS and parasitic infections are essential to improve the overall health and well-being of individuals living with HIV/AIDS in this region.

Availability of data and materials

The datasets used and/or analysed during the current study are in the manuscript and available from the corresponding author on reasonable request.

Abbreviations

Acid fast bacilli

Acquired immuno deficiency syndrome

Anti retro viral treatment

Cluster for differentiation

Debre markos compressive specialized hospital

Finote selam general hospital

Lumamie distirict hospital

Yejuba district hospital

Central nervous system

Human immunodeficiency virus

People living with human immunodeficiency virus

Human thymus lymphocyte virus

• Intestinal parasite

Ministry of Health

Stastical package of social science

Revolution per minute

United Nation on ADIS Program

Highly active antiretroviral therapy

People living with HIV/ADIS

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Acknowledgements

We express our gratitude to the Department of Medical Laboratory Sciences, Health Science College, Debre Markos University for facilitating the study. We would also like to extend our deepest appreciation to the staff of hospitals and health centers, particularly those in the ART department, as well as the study participants who were involved in the research.

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ME and AA were responsible for designing the study, collecting, analysing the data, a interpreting the results, and writing the initial manuscript. GAA and AF were involved in analysing and critically reviewing the manuscript. HB supervised the data collection process and ensured the quality of the data. All authors actively participated in preparing and revising the final manuscript, and they all read and approved the final version of the manuscript.

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This research has been performed by the Declaration of Helsinki. Ethical clearance was obtained from the ethical review committee of the Department of Medical and Laboratory Sciences, College of Medicine and Health Sciences, Debre Markos University, Ethiopia (DMLS/ser/104/2022). Support letters and permission were obtained from the respective hospitals as well.

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Endalamaw, M., Alemneh, A., Amare, G.A. et al. Magnitude of intestinal parasitic infections and its determinants among HIV/AIDS patients attending at antiretroviral treatment centers in East and West Gojam Zones, Northwest, Ethiopia: institution based cross-sectional study. AIDS Res Ther 21 , 32 (2024). https://doi.org/10.1186/s12981-024-00618-3

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Received : 05 February 2024

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DOI : https://doi.org/10.1186/s12981-024-00618-3

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