Introduction
Continuing and re-emerging HIV-epidemics have been reported among men who have sex with men (MSM) in the industrialized world [1–4]. In Africa, Latin America and Asia, studies have shown high HIV-prevalence in MSM [1,4–8]. MSM HIV-incidence estimates are scarce. Few MSM cohort studies exist, and estimates are usually based on detuning seroprevalent specimens [9]. MSM cohort studies from Amsterdam and Sydney showed yearly HIV-incidence around 1% [10,11], but in MSM in HIV-prevention trials this was 2.1–2.7% [12,13]. Detuned yearly HIV-incidence estimates were 1.5–5.0% in Europe [10,14–16], 4.2% in the United States [17], 5.1% in Central America [18] and 3.0% in China [19]. An acute HIV-infection study in Thai MSM found a yearly incidence of 2.7% [20]. However, methodological difficulties of detuned testing may have inflated HIV-incidence estimates [21]. HIV risk factors in MSM were mostly established during the early years of the epidemic, and current information is sparse. In this article, we report recent HIV-prevalence, incidence and risk factors in a cohort of MSM in Bangkok.
Methods
Study population
Eligible men were at least 18 years old, Thai national, Bangkok resident, had penetrative male-to-male sex in the past 6 months and available for 4-monthly follow-up for ≥3 years. Men were recruited from HIV testing services, entertainment venues (bars, discos, sauna's), the Internet and word of mouth. Men received pretest and posttest HIV and risk behaviour counselling during every study visit based on the FHI360 curriculum [22]. Those testing HIV-positive were referred for antiretroviral treatment (ART) according to Thai national guidelines [23]. Those with active sexually transmitted infections (STI) were treated and those without hepatitis B virus (HBV) immunity were offered HBV vaccination, free of charge. Study location was a dedicated clinic in a central Bangkok hospital.
Measures
HIV-infection was determined at baseline and every 4 months thereafter using OraQuick HIV-1/2 Rapid Test (OraSure Technologies, Bethlehem, Pennsylvania, USA), and if reactive, confirmed according to Thai national guidelines with three rapid tests on blood [Determine HIV-1/2; Abbott Laboratories, Tokyo, Japan; DoubleCheck II HIV-1&2; Organics, Yavne, Israel (after 02/2011 replaced by SD-Bioline HIV-1/2 3.0; Standard Diagnostics, Kyonggi-do, South-Korea); Capillus HIV-1/HIV-2; Trinity Biotech, Jamestown, New York, USA (after 11/2008 replaced by Core HIV-1/2, Birmingham, UK)]. The midpoint between the last HIV-negative and first HIV-positive date was considered the seroconversion date. Baseline blood specimens were tested for antihepatitis A virus (anti-HAV), anti-HBV, HBV-core antigen (HBcAg), HBV-surface antigen (HBsAg), and antihepatitis C virus (anti-HCV) (Murex anti-HAV, anti-HBV, HBcAg, HBsAg, anti-HCV; Murex Biotec, Dartford, UK) and antiherpes simplex virus type-1 and 2 (anti-HSV-1, 2) (HerpeSelect 1 and 2 Elisa; Focus Diagnostics, Cypress, California, USA), and for Treponema pallidum by rapid plasma regain (RPR) assay (Macro-Vue RPR 18 mm Circle Card Test; Becton Dickinson Microbiology Systems, Sparks, Maryland, USA) confirmed by immunochromatography (IC) (Determine Syphilis-TP; Abbott Laboratories). Persons with RPR at least 1 : 8 and positive IC were considered T. pallidum positive (current or past infection) [24]. Baseline urine was drug-use tested (TOX/See Drug Screen Test; Bio-Rad Laboratories, Hercules, California, USA); and rectal swabs for Neisseria gonorrhoeae and Chlamydia trachomatis by PCR. Demographic and behavioural data were collected at baseline and every 4 months thereafter using audio-computer-assisted self-interviewing. Circumcision was assessed clinically at baseline.
Statistics
Bivariate risk factors for prevalent HIV-infection were evaluated using odds ratios (OR) and 95% confidence intervals (CI). Variables with P-values of less than 0.05 were entered in multivariate stepwise backward logistic regression analyses to identify independent risk factors for prevalent infection. Crude HIV-incidence was calculated as the number of new infections divided by the number of person-years of follow-up, along with exact Poisson 95% CI. For time-dependent variables, person-years contributions were based on reports of the behaviour during the prior interval. The 60 months cumulative HIV-incidence was estimated using Kaplan–Meier analysis. Cox proportional hazard analysis using baseline demographic and behavioural characteristics as fixed and past 4-month behavioural risks as time-dependent variables (Table 1) was applied to evaluate bivariate and multivariate risk factors for incident HIV-infection (SAS, Version 9; SAS Institute Inc., Cary, North Carolina, USA).
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Table 1-a: Demographic and behavioral characteristics and bivariate and multivariate analyses of risk factors for HIV-prevalence and incidence in a cohort of men who have sex with men in Bangkok, Thailand, 2006–2012.
Table 1-b: Demographic and behavioral characteristics and bivariate and multivariate analyses of risk factors for HIV-prevalence and incidence in a cohort of men who have sex with men in Bangkok, Thailand, 2006–2012.
Table 1-c: Demographic and behavioral characteristics and bivariate and multivariate analyses of risk factors for HIV-prevalence and incidence in a cohort of men who have sex with men in Bangkok, Thailand, 2006–2012.
Human patients review
The study protocol was reviewed and approved by the Thailand Ministry of Public Health Ethical Review Committee and by a CDC Institutional Review Board. Written informed consent was obtained from all participants.
Results
Baseline demographic and behavioural characteristics
Between April 2006 and November 2010, 1977 men were screened, 1764 (89.2%) were eligible, and 1744 (98.9%) enrolled. The on-going 36-months retention rate was 76.1%. Participant's median and mean ages were 26 years (range 18–56 years). During 4 months prior to baseline, binge drinking was reported by 11.9%, use of ‘club’ drugs, 10.8%, nitrate inhalation, 10.9%, drug use for sexual pleasure, 17.6%, erectile dysfunction drug (EDD) use, 11.6%, sex with women, 9.1%, prereceptive and postreceptive anal cleansing, 77.3%, at least six male sexual partners, 40.1%, and inconsistent condom use, 54.0%. Having paid or received money for sex was reported by 13.9 and 19.0%, respectively. At baseline, receptive or both receptive and insertive anal intercourse was reported by 64.0%, group sex by 35.6% and a history of sexual coercion by 17.3%. Fifty percent ever had an HIV-test and 10.3% had been circumcised (Table 1).
Prevalence of baseline sexually transmitted infection and drug-use reactivity
Of those tested, 5.6% had evidence of rectal N. gonorrhoeae and 8.7% of rectal C. trachomatis (Table 1). Anti-HAV, anti-HBV, and anti-HCV prevalence was 27.1, 46.4, and 0.8%, respectively; 9.2% were HBV-antigenemic. Anti-HSV-1 and anti-HSV-2 was found in 56.5 and 21.3%, respectively and 4.7% tested positive for T. pallidum. Drug-use positive urine was found in 4.5%, mostly due to benzodiazepine reactivity.
HIV-prevalence and incidence
Baseline HIV-prevalence was 21.3%. Among 18–21-year olds it was 15.9%, among 22–29 year olds, 22.6% and among at least 30 year olds, 22.4%. The overall HIV-incidence was 5.9 per 100 person-years. Among 18–21 years olds it was 8.8, among 22–29 year olds, 6.4 and among at least 30 year olds, 3.7 per 100 person-years (Table 1). After 60 months of follow-up, the cumulative HIV-incidence was 23.9%. Among 18–21 year olds this was 31.3%, among 22–29 year olds, 26.3% and among at least 30 year olds, 15.2% (Fig. 1).
Fig. 1: Sixty months cumulative HIV-incidence (Kaplan–Meier method) in a cohort of men who have sex with men, Bangkok, Thailand, 2006–2012, by age group.
Risk factors for HIV-prevalence and incidence
In multivariate logistic regression analysis, older age, secondary/vocational education, not studying, nitrite inhalation, drug use for sexual pleasure, receptive anal intercourse, sexual coercion, no prior HIV-test, and baseline anti-HSV-1, 2, and T. pallidum positivity were significantly and independently associated with prevalent HIV-infection (Table 1).
In multivariate Cox proportional hazard analysis including data collected until July 2012, younger age, living alone or with roommate, drug use for sexual pleasure, inconsistent condom use, receptive anal intercourse, group sex, and baseline anti-HSV-1, 2 and T. pallidum positivity were significantly and independently associated with incident HIV-infection. Having no anal intercourse partners was inversely associated with incident HIV-infection (Table 1).
Discussion
This study documents an explosive epidemic of HIV-infection in Bangkok MSM. Baseline HIV-prevalence was 21.3% and HIV-incidence 5.9 per 100 person-years. This HIV-incidence is among the highest reported since the initial outbreak of HIV-infection among MSM in the Western world [25,26] and only comparable to current incidence among MSM in Kenya [27] and to that estimated among inner-city black MSM in the United States [17].
Risk factors consistent across HIV-prevalence and incidence were drug use for sexual pleasure, receptive anal intercourse, and anti-HSV-1, 2 and T. pallidum positivity. These are well established risk factors [28–31], but drug use, particularly of methamphetamine (‘crystal-ice’), is an emerging risk in MSM in Asia [4,7,28,29,32]. Methamphetamine injection has been reported by MSM in the USA and Australia [28], but drug injection was rare in our cohort. Among Thai MSM, methamphetamine is usually smoked, often combined with EDD to prolong sexual intercourse and pleasure. This behaviour may cause anogenital trauma, whereas drug impairment may lead to inconsistent condom use and ultimately to HIV transmission. Prevention and education about drug use, possibly in combination with harm reduction strategies, should therefore be included in HIV prevention programs for MSM. As expected, older age was associated with HIV-prevalence, whereas younger age was associated with HIV-incidence. Younger age has been identified as an HIV risk factor in previous studies [33] and may be associated with increased risk taking and a higher background number of susceptible and acutely HIV-infected persons. Other known risk factors for HIV-prevalence included lower education, history of sexual coercion and lack of prior HIV-testing [34–38]. A remaining risk factor for incident HIV-infection was inconsistent condom use, while not having any anal intercourse partners was protective against HIV-infection. Consistent and correct use of condoms is an efficient method to prevent HIV-infection in MSM, and their use, in combination with water-based gels, should be promoted [39]. However, avoidance of any anal intercourse, if at all possible, appears to be a more effective prevention method.
A remarkable finding was the high prevalence of preanal and postanal receptive cleansing by Thai MSM. Cleansing usually consists of inter-rectal showering with water before and after receptive anal intercourse. Pre and postreceptive anal intercourse cleansing was more often reported than receptive anal sex, possibly as a result of underreporting and stigma associated with being receptive during anal sex. Because of collinearity with anal intercourse, cleansing could not be evaluated in our analyses. Nevertheless, these findings are important for future rectal microbicide studies as cleansing may confound or interfere with possible microbicide efficacy. Another area of interest is male circumcision. However, circumcision was rare in this cohort and was not associated with prevalent or incident HIV-infection. When evaluated separately among predominantly anal insertive or receptive men no association with HIV-infection was found.
Our study has several limitations. Men were not randomly selected and may not be perfectly representative of the Bangkok MSM population. Another limitation was the absence of incident STI, and their association with HIV-infection could not evaluated. Our study had several strengths as well, including the long follow-up time and the dual evaluation of risk factors for HIV-prevalence and incidence in one design.
Given the high and continuing HIV-incidence in our cohort, particularly among young MSM, this group should be considered for recently proven daily oral antiretroviral preexposure chemo-prophylaxis (PrEP) for the prevention of HIV-infection [40]. Since the demographic and behavioural risk factors for HIV-acquisition in this cohort are well described, a targeted HIV prevention program consisting of behavioural and biomedical interventions for those at the highest risk should be considered. Such a program should include careful evaluation of PrEP efficiency by comparing HIV-incidence with historical information or in a wait-list control group design. In addition, peer-driven adherence support and monitoring of drug safety and tolerance as well as of drug resistance in break-through infections should be included.
The explosive HIV-epidemic in Bangkok MSM underscores the need for innovative and increased efforts to prevent HIV-infection in this population. Simultaneous and combined implementation of scientifically proven interventions, such as increased HIV-testing [38], ART for prevention [41], PrEP [40], together with educational and motivational programs for protective behavior and unlimited access to condoms and nonlatex deteriorating gels may decrease transmission [39]. Finally, discriminatory policies and stigmatizing practices that hinder access to HIV-prevention services for MSM should be eliminated.
Acknowledgements
The authors kindly acknowledge the support of the personnel of the Thailand MOPH-US CDC Collaboration and the Silom Community Clinic. The authors also would like to express their gratitude towards the participants in the study for their time and dedication.
Role of the study sponsor: The US Centers for Disease Control and Prevention sponsored this study. The study sponsor reviewed and approved of the study protocol and of this article. The study sponsor had no role in the analysis or interpretation of the data or in the writing of the article.
Author contributions: F.V.G., P.A. and J.T. conceived the study; F.V.G. oversaw study implementation and drafted the article; W.T., W.W. and P.M. oversaw data collection, performed data management and statistical analysis; J.M., W.C. and P.S. oversaw and performed laboratory testing; S.C. and A.V. were responsible for study implementation and clinical data collection. All authors reviewed and edited the manuscript and approved of the final version. F.V.G. had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Disclaimer: The findings and conclusions presented in this article are those of the authors and do not necessarily represent the views of the US Centers for Disease Control and Prevention.
Conflicts of interest
There are no conflicts of interest.
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