Baral S, Sifakis F, Cleghorn F, Beyrer C. Elevated risk for HIV infection among men who have sex with men in low- and middle-income countries 2000-2006: a systematic review. PLoS 2007 Dec;4(12):e339.
To summarize available data on the global epidemic of HIV among men who have sex with men (MSM) in low- and middle-income countries and relation to HIV prevalence in the general population.
A systematic review and meta-analysis.
The authors searched databases including PubMed, EMBASE, EBSCO, and the Cochrane Database of Systematic Reviews. Inclusion criteria for studies were determined a priori to be: 1. studies including HIV prevalence data among MSM populations (including homosexual, bisexual, male sex workers, transgender, and other country-specific populations of MSM); 2. publication in a peer-reviewed journal; an abstract at a conference with a peer-reviewed, blinded abstract selection process; 3. listed details regarding data sampling techniques; 4. data collection started since January 1, 2000; 5. studies in low and middle-income countries; and studies taking place in countries where UNAIDS has calculated a general population prevalence for 2006. Studies not published in a peer-reviewed journal, though commissioned by government managed epidemiologic monitoring agencies such as European Centre for the Epidemiological Monitoring of AIDS (EuroHIV) or the US Centers for Disease Control and Prevention (CDC), also were included. Although the authors do not provide their entire search strategy, they describe using the following medical subject heading (MESH) terms in PubMed and as keywords in the other databases: "Homosexual, Men" OR "Homosexual" which were cross-referenced with the key word (AND) "HIV" OR the MESH term "Human Immunodeficiency Virus" and limited to reports in the English language published between October 3, 2000, and October 3, 2006, and pertaining to individuals 15 years of age and older. The exclusion criteria were studies with a sample size less than 50, self-reported HIV status rather than serologic testing, and samples that were a subset of another population used in another study. Eligible studies with 0% HIV prevalence among MSM were included. Both online and CD-based abstract volumes were searched from the International AIDS Conference; The Conference on HIV Pathogenesis, Treatment, and Prevention; and the Conference on Retroviruses and Opportunistic Infections with similar restrictions using search terms including "men who have sex with men," "MSM," "homosexual," "bisexual," OR "transgender."
In the database searches, the authors initially identified 1395 articles (including 96 reviews - it was not stated whether these were narrative reviews or systematic reviews). They examined the full texts of 115 articles, and found that 22 contained data from at least one study that fulfilled their inclusion criteria. Of the 779 conference abstracts reviewed, 524 were unique and 49 met all the inclusion and exclusion criteria, though six were later excluded due to the inability to contact the respective study authors for methodologic clarification, or an inability to retrieve background prevalence of HIV in that country. An additional 16 studies were retrieved from the most recent full report from EuroHIV. In all, 83 studies from 58 unique reports were used in the meta-analysis describing MSM populations in 38 countries.
There was an aggregate total of 63,538 participants from 38 different low- and middle-income countries (as defined by the World Bank). The participants were males ≥15 years old. Data regarding prevalence and total sample size were obtained from each of the studies that met inclusion criteria. Aggregate values were calculated for each country by combining the absolute number of MSM with HIV and without HIV. As only raw data were collected from the studies, prevalence estimates of HIV among MSM were determined for each country with 95% confidence intervals (CIs). A combined prevalence estimate was calculated by combining a weighted HIV prevalence among MSM for each country. The pooled estimate was weighted according to the sample size of MSM studied in that country's sampling.
Estimates of HIV prevalence ,from UNAIDS were used for overall prevalence in individual countries and prevalence among MSM within those countries was derived from the abstracted studies; the odds ratio (OR) between being MSM and HIV infection was calculated. The overall pooled OR and pooled ORs within strata classifying countries were calculated with a random effects meta-analysis.
Using studies from all 38 countries, MSM had a 19.3 (95% CI 18.8-19.8) times greater odds of having HIV compared with background populations. When the pooled OR was stratified by prevalence levels of countries, very low-prevalence countries had the highest OR of infection in MSM compared with the general population, 58.4 (95% CI 56.3-60.6); in low-prevalence countries the OR was 14.4 (95% CI 13.8-14.9); and in medium- to high-prevalence settings it was 9.6 (95% CI 8.9- 10.2). The OR was higher where transmission in injection drug users (IDUs) was not a substantial component of the HIV epidemic: 24.4 (95% CI 23.7-25.2) compared with 12.8 (95% CI 12.3-13.4) where IDUs are a substantial driver of the local HIV epidemic. ORs for HIV infection among MSM were similar among UNAIDS classified low-level (24.5, 95% CI 22.8-26.3) and concentrated (23.5, 95% CI 22.9-24.1) epidemics, and both ratios were higher than in generalized epidemics (10.8, 95% CI 10.3- 11.4). Significant differences in ORs for HIV infection among MSM were seen when comparing low- and middle-income countries; low-income countries had an OR of 7.8 (95% CI 7.2-8.4), whereas middle-income countries had an OR of 23.4 (95% CI 22.8-24.0). Finally, when stratifying by region, an OR for HIV among MSM in the Americas was 33.3 (95% CI 32.3-34.2), 18.7 (95% CI 17.7-19.7) for Asia, 1.3 (95% CI 1.1-1.6) for Europe, and 3.8 (95% CI 3.3-4.3) for Africa.
The authors conclude that MSM have a markedly greater risk of being infected with HIV compared with general population samples from low- and middle-income countries in the Americas, Asia, and Africa. ORs for HIV infection in MSM are elevated across prevalence levels by country and decrease as prevalence in the general population increases, but remain 9-fold higher in medium-high prevalence settings. MSM from low- and middle-income countries are in urgent need of prevention and care, and appear to be both understudied and underserved.
The systematic review and meta-analysis are of high quality. This review meets 12 of the 16 criteria on the QUOROM checklist for assessing the quality of reports of meta-analyses of randomized controlled trials, and since this is a review of prevalence studies, some of those criteria do not apply. The chief limitation of the review is that only English-language articles were included in the search, but the authors state that an informal search of non-English databases did not identify a study not published in an English-language journal.
Aside from the formal quality of the review, there are greater concerns, as the authors acknowledge, with the quality of the studies themselves. MSM in many developing countries are often difficult to access and to study because of criminalization of their behavior, the social stigma associated with their behaviors and identities, participant safety concerns in some settings, and low levels of self-identification among MSM. These barriers likely limited both the number and quality of studies in the literature - only a few lower-income countries, including Mexico, Brazil, Thailand, and Peru, have systematically surveyed MSM. The majority of studies cited in this analysis are convenience samples and cross-sectional in design, and so may not be representative of MSM. To determine a corollary of risk for HIV infection among MSM in low- and middle-income countries, the authors used UNAIDS general population prevalence estimates for each country as the unexposed population to compute ORs. Because of the lack of controls, issues affecting internal validity could not be formally controlled for in the review. MSM tend to congregate in urban areas, at least partially explaining why the majority of reported studies are urban; again, this may limit generalizability. In very populous countries such as China and India, there may be even more marked differences between urban and rural areas in HIV prevalence and in reporting of MSM behaviors.
An editorial note on the use of odds ratios in the review: The authors mention the possibility of a ceiling effect in using relative measures of association like the odds ratio but do not clarify what this might mean for their results. To clarify with an example of a country with high prevalence (>5%), the odds ratio for MSM if the MSM prevalence in such a country were as high as, say, 1 in 4 or more (the MSM prevalence in San Francisco), the odds ratio would be constrained to be below 7 (OR for 25% prevalence divided by 5% prevalence is approximately 20/3). So in high-prevalence countries this ceiling effect could be quite pronounced.
This is probably the first meta-analysis of HIV survey data collected from MSM participants in low- to middle-income countries. Overall, the odds of having HIV infection are markedly and consistently higher among MSM than among the general population of adults of reproductive age across Asia, Africa, the Americas, and the former Soviet Union. The stratification of the pooled OR estimate revealed some general differences in risk status among MSM globally. The highest OR for HIV infection was found in the Americas, at 33.3. It was lower, but still extremely high, in Asia at 18.7, lower still in Africa at 3.8, and lowest in Eastern Europe at 1.3. The authors believe that the relatively outlying result from Eastern Europe is likely due to comparing MSM with populations where IDUs are the main driver of HIV. There is also a shortage of data from Eastern Europe. No peer-reviewed published report or abstract meeting the authors' inclusion criteria was found in Eastern Europe. The most recent EuroHIV surveillance report served as the primary source for these data. Since an unknown but potentially significant number of MSM in this region may also be IDUs, estimating the attributable risk fraction for these differing behaviors is difficult. What is clear is the need for more effort to characterize the risks for MSM in this region. The very high rates in the Americas and Asia were by far the best evidenced, suggesting that these epidemics among MSM are real, and that these men are indeed at markedly greater risk than heterosexuals in these settings. Data regarding MSM in Africa were the sparsest, but are beginning to emerge. Recent reports of HIV risks (if not rates) among MSM were found from Uganda, Zambia, Sudan, and Nigeria, though not all met inclusion criteria for this analysis. These epidemics appear to be driven, in part, by marked stigma and homophobia in these settings and by a lack of specific prevention strategies. The UNAIDS classification of HIV epidemics was designed, in part, to provide guidance on the type of surveillance that should be conducted in a country. However, the absence of a difference in the odds of HIV infection among MSM between concentrated and low-level epidemics suggests that this classification system is currently not ideal for measuring the increased risk of specific subsets of the population. The accuracy of HIV epidemic levels may be improved as more comprehensive prevalence data of specific vulnerable populations such as MSM become available.
These results constitute a clear call to action on three fronts: surveillance, research, and prevention. The various subgroup analyses completed for this study may not necessarily explain complex differences in global HIV epidemic dynamics, but they do demonstrate that high HIV prevalence rates among MSM are not limited to any one epidemic level, prevalence category, region, or income level. HIV surveillance efforts should take into account the high burden of HIV among MSM and expand surveillance to include them in countries where they are not now included. Social science, epidemiologic, and behavioral research should use population-based sampling methods and standardized data collection tools to assess prevalence of HIV risk behaviors, knowledge about HIV, and social and sexual network interactions, and the roles individual and partner circumcision status may play in male-to-male HIV transmission and acquisition dynamics. Ethnographic assessments could further describe the cultural and behavioral nuances of MSM globally and refine data collection instruments. Human rights advocacy and cessation of discrimination against MSM could afford greater access to HIV prevention and education services and are an urgent priority in much of the world. Although these data indicate that these MSM populations are in desperate need of targeted prevention campaigns, social intolerance currently limits prevention efforts. UNAIDS estimates that in 2005, fewer than one in 10 MSM globally had access to appropriate HIV prevention services.(1) Notably, there exists a risk that demonstrating high HIV prevalence rates among MSM will further contribute to stigma. However, prevention expenditures are generally allocated based on need; thus, the risk of increasing stigma must be balanced by the potential benefits of successfully advocating for dedicated funding resources for MSM.
- UNAIDS. Report on the Global AIDS Epidemic. Geneva, 2006