Frits van Griensven

Global epidemiology of HIV infection in men who have sex with men

Epidemics of HIV in men who have sex with men (MSM) continue to expand in most countries. We sought to understand the epidemiological drivers of the global epidemic in MSM and why it continues unabated. We did a comprehensive review of available data for HIV prevalence, incidence, risk factors, and the molecular epidemiology of HIV in MSM from 2007 to 2011, and modelled the dynamics of HIV transmission with an agent-based simulation. Our findings show that the high probability of transmission per act through receptive anal intercourse has a central role in explaining the disproportionate disease burden in MSM. HIV can be transmitted through large MSM networks at great speed. Molecular epidemiological data show substantial clustering of HIV infections in MSM networks, and higher rates of dual-variant and multiple-variant HIV infection in MSM than in heterosexual people in the same populations. Prevention strategies that lower biological transmission and acquisition risks, such as approaches based on antiretrovirals, offer promise for controlling the expanding epidemic in MSM, but their potential effectiveness is limited by structural factors that contribute to low health-seeking behaviours in populations of MSM in many parts of the world.

The global epidemic of HIV infection among men who have sex with men.

Purpose of reviewIn the last few years, there have been reports of new, newly identified and resurging epidemics of HIV infection among men who have sex with men (MSM). This article reviews and summarizes the global epidemic of HIV infection among MSM. Recent findingsIn the Western world, the increase in notifications of new HIV infections among MSM is continuing. Steep increases in reports of new HIV diagnoses among MSM were also seen in the developed economies of East Asia. In the developing world, epidemiologic studies have now established the presence of MSM populations in Africa, China and Russia and a high HIV prevalence among them. High and increasing HIV prevalence was also reported from South and Southeast Asia, and Latin America and the Caribbean. SummaryHIV continues to spread among MSM on a global level. Current prevention efforts have been unable to contain or reduce HIV transmission in this population. Additional behavioral and biomedical interventions are urgently needed.

Central Nervous System Viral Invasion and Inflammation During Acute HIV Infection

BACKGROUND Understanding the earliest central nervous system (CNS) events during human immunodeficiency virus (HIV) infection is crucial to knowledge of neuropathogenesis, but these have not previously been described in humans. METHODS Twenty individuals who had acute HIV infection (Fiebig stages I-IV), with average 15 days after exposure, underwent clinical neurological, cerebrospinal fluid (CSF), magnetic resonance imaging, and magnetic resonance spectroscopy (MRS) characterization. RESULTS HIV RNA was detected in the CSF from 15 of 18 subjects as early as 8 days after estimated HIV transmission. Undetectable CSF levels of HIV (in 3 of 18) was noted during Fiebig stages I, II, and III, with plasma HIV RNA levels of 285651, 2321, and 81978 copies/mL, respectively. On average, the CSF HIV RNA level was 2.42 log(10) copies/mL lower than that in plasma. There were no cases in which the CSF HIV RNA level exceeded that in plasma. Headache was common during the acute retroviral syndrome (in 11 of 20 subjects), but no other neurological signs or symptoms were seen. Intrathecal immune activation was identified in some subjects with elevated CSF neopterin, monocyte chemotactic protein/CCL2, and interferon γ-induced protein 10/CXCL-10 levels. Brain inflammation was suggested by MRS. CONCLUSIONS CSF HIV RNA was detectable in humans as early as 8 days after exposure. CNS inflammation was apparent by CSF analysis and MRS in some individuals during acute HIV infection.

Impact of Multi-Targeted Antiretroviral Treatment on Gut T Cell Depletion and HIV Reservoir Seeding during Acute HIV Infection

Background Limited knowledge exists on early HIV events that may inform preventive and therapeutic strategies. This study aims to characterize the earliest immunologic and virologic HIV events following infection and investigates the usage of a novel therapeutic strategy. Methods and Findings We prospectively screened 24,430 subjects in Bangkok and identified 40 AHI individuals. Thirty Thais were enrolled (8 Fiebig I, 5 Fiebig II, 15 Fiebig III, 2 Fiebig IV) of whom 15 completed 24 weeks of megaHAART (tenofovir/emtricitabine/efavirenz/raltegravir/maraviroc). Sigmoid biopsies were completed in 24/30 at baseline and 13/15 at week 24. At baseline, the median age was 29 years and 83% were MSM. Most were symptomatic (87%), and were infected with R5-tropic (77%) CRF01_AE (70%). Median CD4 was 406 cells/mm3. HIV RNA was 5.5 log10 copies/ml. Median total blood HIV DNA was higher in Fiebig III (550 copy/106 PBMC) vs. Fiebig I (8 copy/106 PBMC) (p = 0.01) while the median %CD4+CCR5+ gut T cells was lower in Fiebig III (19%) vs. Fiebig I (59%) (p = 0.0008). After 24 weeks of megaHAART, HIV RNA levels of <50 copies were achieved in 14/15 in blood and 13/13 in gut. Total blood HIV DNA at week 0 predicted reservoir size at week 24 (p<0.001). Total HIV DNA declined significantly and was undetectable in 3 of 15 in blood and 3 of 7 in gut. Frequency of CD4+CCR5+ gut T cells increased from 41% at baseline to 64% at week 24 (p>0.050); subjects with less than 40% at baseline had a significant increase in CD4+CCR5+ T cells from baseline to week 24 (14% vs. 71%, p = 0.02). Conclusions Gut T cell depletion and HIV reservoir seeding increases with progression of AHI. MegaHAART was associated with immune restoration and reduced reservoir size. Our findings could inform research on strategies to achieve HIV drug-free remission.

Evidence of a previously undocumented epidemic of HIV infection among men who have sex with men in Bangkok, Thailand

Background:The HIV prevalence and associated risk behaviours in Thai men who have sex with men (MSM) are unknown. This information is crucial to inform and implement targeted preventive interventions for this population. Methods:A cross-sectional assessment, using venue–day–time sampling, was conducted. Participants were 1121 Thai men who were 18 years or older, were residents of Bangkok, and reported anal or oral sex with a man during the past 6 months. Oral fluid specimens were tested for HIV antibody. Demographic and behavioural data were collected using an interviewer-administered Palm based automated questionnaire. Results:HIV prevalence was 17.3% (194 of 1121). Mean age was 26.9 years (median 25 years), and university education was completed by 42.5%. Sex with men and women during the past 6 months was reported by 22.3%; sex with a woman ever, 36%; and unprotected sexual intercourse during the past 3 months, 36.0%. Alcohol use during the past 3 months was common (73.7%); drug use was rare (2.5%). Multivariate logistic regression analyses showed lower education, recruitment from a park, self-identification as homosexual, receptive and insertive anal intercourse, more years since first anal intercourse, and more male sex partners to be significantly and independently associated with HIV prevalence. Conclusions:HIV infection is common among MSM in Bangkok. HIV prevention programs are urgently needed to prevent further spread of HIV in this young and sexually active population.

Trends in HIV Prevalence, Estimated HIV Incidence, and Risk Behavior Among Men Who Have Sex With Men in Bangkok, Thailand, 2003–2007.

Background:Men who have sex with men (MSM) continue to be at high risk for HIV infection. Here we evaluate trends in HIV prevalence, estimated HIV incidence, and risk behavior among MSM in Bangkok, Thailand. Methods:Between 2003 and 2007, 3 biennial cross-sectional HIV prevalence assessments were conducted among MSM in Bangkok, Thailand, using venue-day-time sampling. Oral fluid was tested for HIV infection; demographic and behavioral data were self-collected using hand-held computers. Estimates of annual HIV incidence in young MSM were derived as follows: (number of HIV infections/sum of [current age-age at start of anal intercourse]) × 100). Logistic and Poisson regression was used to evaluate trends in HIV prevalence, estimated HIV incidence, and risk behavior. Findings:The overall HIV prevalence increased from 17.3% in 2003 to 28.3% in 2005 to 30.8% in 2007 (P < 0.001 for trend). The estimated HIV incidence among young MSM increased from 4.1% in 2003 to 6.4% in 2005, to 7.7% in 2007 (P < 0.02 for trend). The increase in HIV prevalence from 2005 to 2007 was not statistically significant. The proportion of men reporting anal sex and casual or steady male sex partners in the past 3 months significantly decreased, whereas the proportion reporting drug use and drug use during sex significantly increased. No increase was observed in the proportion of men reporting consistent condom use. Interpretation:Our data suggest that after a strong increase from 2003 to 2005, the HIV prevalence among MSM in Bangkok may have begun to stabilize. Given the continuing high levels of risk behavior and the estimated high HIV incidence in young MSM, additional HIV preventive interventions are necessary.

Sexual initiation, substance use, and sexual behavior and knowledge among vocational students in northern Thailand.

CONTEXT Thailand has undergone dramatic social changes in the last two decades, yet little is known about factors related to sexual initiation among adolescents. METHODS A survey using the audio computer-assisted self-interviewing method was conducted to assess social and demographic characteristics, substance use, sexual behavior, and knowledge of HIV and STIs among 1,725 vocational school students aged 15-21 living in northern Thailand. Gender differences for these factors were evaluated using chi-square and Mann-Whitney U tests. Multivariate survival analysis using Cox proportional hazards models assessed associations between these variables and sexual initiation for each gender. RESULTS Males initiated sexual intercourse at an earlier age than females (median ages of 17 and 18, respectively). At any given age, sexual initiation was associated with having a nonagricultural background and using alcohol or methamphetamine (adjusted rate ratios, 1.3-2.9). For males, initiation was also associated with having parents who did not live together, having a friend as a confidant, tobacco use, high perceived risk for HIV and high STI knowledge (1.3-1.7). For females, other factors associated with earlier initiation were younger age at interview, living away from family, lacking a family member as a confidant, high perceived risk for STIs and ever having smoked marijuana (1.3-2.4). CONCLUSIONS Interventions to ameliorate the adverse consequences of early sexual initiation need to address social influences such as parents and peer groups. Programs should identify and target high-risk subgroups, such as those who are sexually experienced at an early age and those engaged in patterns of generalized risk-taking.

HIV Type 1 Incidence Estimates by Detection of Recent Infection from a Cross-Sectional Sampling of Injection Drug Users in Bangkok: Use of the IgG Capture BED Enzyme Immunoassay

Development of serologic tests to detect recent HIV-1 infection has generated worldwide interest in applying this approach to estimate incidence. We previously devised an IgG-capture BED-EIA (or BED-CEIA) that detects increasing levels of anti-HIV IgG following seroconversion to identify recent infection and to estimate incidence among persons infected with diverse HIV-1 subtypes worldwide. Injection drug users (IDUs; n = 1969) were screened in 1996 for participation in a prospective cohort study. Serum specimens from 594 IDUs were HIV-1 seropositive (30.2%) and were tested with the BED-CEIA. The proportion of recent infections and estimated incidence by different epidemiological risk factors were compared with incidence data measured from the prospective cohort. Of 594 HIV-1-seropositive specimens, 113 (19%) were identified as recent infections. Overall, the estimated annual incidence among persons screened was 17.3%/year (95% CI, 12.8-24.2%/year) compared with 9.0%/year (95% CI, 6.7-11.9%/year) measured from the prospective cohort during the same time period. Estimated incidence was higher among younger aged and unemployed IDUs as well as among those who injected more frequently, confirming previously reported risk factors from this prospective cohort. As persons screened from a cross-sectional sampling probably have higher risk for HIV than selected uninfected individuals who choose to participate and receive risk reduction counseling in a longitudinal cohort study, use of this or other serologic testing strategies to identify populations with high incidence (such as for HIV vaccine trials) may overestimate incidence measured from prospective cohorts.

Inconsistent Condom Use Among Young Men Who Have Sex With Men, Male Sex Workers, and Transgenders in Thailand

Young men who have sex with men (MSM) are at risk for HIV infection. We investigated inconsistent condom use among 827 sexually active young MSM (15-24 years), enrolled using venue-day-time sampling in Bangkok, Chiang Mai and Phuket, Thailand. Data was collected using palmtop computer-assisted self-interviewing. Of participants, 33.1% were regular MSM, 37.7% were male sex workers (MSWs) and 29.1% were transgenders (TGs). Of MSM, 46.7%, of MSWs, 34.9% and of TGs, 52.3% reported recent inconsistent condom use. In multivariate analysis, receptive anal intercourse (MSM, MSWs), receptive and insertive anal intercourse, living alone and a history of sexual coercion (MSWs), not carrying a condom when interviewed (MSM, TGs), lower education, worrying about HIV infection and a history of sexually transmitted infections (TGs) were significantly and independently associated with inconsistent condom use. Interventions for young MSM are needed and must consider the distinct risk factors of MSM, MSWs, and TGs.

Sexual health risks among young Thai women: implications for HIV/STD prevention and contraception.

This paper examines factors that may place female Thai adolescents and young adults at risk for HIV, sexually transmitted diseases (STDs), and unintended pregnancies. A total of 832 female vocational students participated in a cross-sectional audio-computer-assisted self-interview (ACASI) survey after providing informed consent. The questionnaire covered: sociodemographic characteristics; knowledge, attitudes, and beliefs related to HIV and STDs; contraceptive practices; sexual experiences and behaviors; and drug use. Oral fluid was tested for HIV antibodies and urine was tested for illicit drugs and for the presence of gonococcal or chlamydial nucleic acids. A total of 359 women (43.1%) reported sexual intercourse history, with an average age at first sex of 17.6 years, and a 2.6 mean number of lifetime sex partners. Twenty-one percent of the entire sample reported coerced sexual contact or intercourse. Among those with sexual intercourse experience, 27.3% (n = 98) had been pregnant and the majority of their most recent pregnancies were terminated. Three tested positive for HIV antibodies. Sexually active young Thai women report behaviors or experiences that may expose them to HIV/STD infection and unintended pregnancy in the future. These include unprotected intercourse, sexual coercion, low levels of contraceptive use, and drug and alcohol use. Culturally appropriate interventions that increase their awareness of and ability to respond to these sexual health risks are needed.