Beryl A. Koblin

Risk factors for HIV infection among men who have sex with men.

Objectives:Risk factors for HIV acquisition were examined in a recent cohort of men who have sex with men (MSM). Design:A longitudinal analysis of 4295 HIV-negative MSM enrolled in a randomized behavioral intervention trial conducted in six US cities. Methods:MSM were enrolled and assessed for HIV infection and risk behaviors semi-annually, up to 48 months. Results:In multivariate analysis, men reporting four or more male sex partners, unprotected receptive anal intercourse with any HIV serostatus partners and unprotected insertive anal intercourse with HIV-positive partners were at increased risk of HIV infection, as were those reporting amphetamine or heavy alcohol use and alcohol or drug use before sex. Some depression symptoms and occurrence of gonorrhea also were independently associated with HIV infection. The attributable fractions of high number of male partners, use of alcohol or drugs before sex, and unprotected receptive anal intercourse with unknown status partners and the same with presumed negative partners accounted for 32.3, 29.0, 28.4 and 21.6% of infections, respectively. Conclusions:The challenge is to develop strategies to identify men in need. Interventions are needed to help men reduce their number of sexual partners, occurrences of unprotected anal intercourse, alcohol or drug use before sex and address other mental health issues.

Effect of aciclovir on HIV-1 acquisition in herpes simplex virus 2 seropositive women and men who have sex with men: a randomised, double-blind, placebo-controlled trial

BACKGROUND Across many observational studies, herpes simplex virus type 2 (HSV-2) infection is associated with two-fold to three-fold increased risk for HIV-1 infection. We investigated whether HSV-2 suppression with aciclovir would reduce the risk of HIV-1 acquisition. METHODS We undertook a double-blind, randomised, placebo-controlled phase III trial in HIV-negative, HSV-2 seropositive women in Africa and men who have sex with men (MSM) from sites in Peru and the USA. Participants were randomly assigned by block randomisation to twice daily aciclovir 400 mg (n=1637) or matching placebo (n=1640) for 12-18 months, and were seen monthly for dispensation of study drug, adherence counselling and measurement by pill count and self-reporting, and risk reduction counselling, and every 3 months for genital examination and HIV testing. The primary outcome was HIV-1 acquisition and secondary was incidence of genital ulcers. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00076232. FINDINGS 3172 participants (1358 women, 1814 MSM) were included in the primary dataset (1581 in aciclovir group, 1591 in control group). The incidence of HIV-1 was 3.9 per 100 person-years in the aciclovir group (75 events in 1935 person-years of follow-up) and 3.3 per 100 person-years in the placebo group (64 events in 1969 person-years of follow-up; hazard ratio 1.16 [95% CI 0.83-1.62]). Incidence of genital ulcers on examination was reduced by 47% (relative risk 0.53 [0.46-0.62]) and HSV-2 positive genital ulcers by 63% (0.37 [0.31-0.45]) in the aciclovir group. Adherence to dispensed study drug was 94% in the aciclovir group and 94% in the placebo group, and 85% of expected doses in the aciclovir group and 86% in the placebo group. Retention was 85% at 18 months in both groups (1028 of 1212 in aciclovir group, 1030 of 1208 in placebo group). We recorded no serious events related to the study drug. INTERPRETATION Our results show that suppressive therapy with standard doses of aciclovir is not effective in reduction of HIV-1 acquisition in HSV-2 seropositive women and MSM. Novel strategies are needed to interrupt interactions between HSV-2 and HIV-1.

Efficacy Trial of a DNA/rAd5 HIV-1 Preventive Vaccine

BACKGROUND A safe and effective vaccine for the prevention of human immunodeficiency virus type 1 (HIV-1) infection is a global priority. We tested the efficacy of a DNA prime-recombinant adenovirus type 5 boost (DNA/rAd5) vaccine regimen in persons at increased risk for HIV-1 infection in the United States. METHODS At 21 sites, we randomly assigned 2504 men or transgender women who have sex with men to receive the DNA/rAd5 vaccine (1253 participants) or placebo (1251 participants). We assessed HIV-1 acquisition from week 28 through month 24 (termed week 28+ infection), viral-load set point (mean plasma HIV-1 RNA level 10 to 20 weeks after diagnosis), and safety. The 6-plasmid DNA vaccine (expressing clade B Gag, Pol, and Nef and Env proteins from clades A, B, and C) was administered at weeks 0, 4, and 8. The rAd5 vector boost (expressing clade B Gag-Pol fusion protein and Env glycoproteins from clades A, B, and C) was administered at week 24. RESULTS In April 2013, the data and safety monitoring board recommended halting vaccinations for lack of efficacy. The primary analysis showed that week 28+ infection had been diagnosed in 27 participants in the vaccine group and 21 in the placebo group (vaccine efficacy, -25.0%; 95% confidence interval, -121.2 to 29.3; P=0.44), with mean viral-load set points of 4.46 and 4.47 HIV-1 RNA log10 copies per milliliter, respectively. Analysis of all infections during the study period (41 in the vaccine group and 31 in the placebo group) also showed lack of vaccine efficacy (P=0.28). The vaccine regimen had an acceptable side-effect profile. CONCLUSIONS The DNA/rAd5 vaccine regimen did not reduce either the rate of HIV-1 acquisition or the viral-load set point in the population studied. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00865566.).

High-risk behaviors among men who have sex with men in 6 US cities: Baseline data from the EXPLORE Study

OBJECTIVES We describe the prevalence of risk behaviors at baseline among men who have sex with men (MSM) who were enrolled in a randomized behavioral intervention trial conducted in 6 US cities. METHODS Data analyses involved MSM who were negative for HIV antibodies and who reported having engaged in anal sex with 1 or more partners in the previous year. RESULTS Among 4295 men, 48.0% and 54.9%, respectively, reported unprotected receptive and insertive anal sex in the previous 6 months. Unprotected sex was significantly more likely with 1 primary partner or multiple partners than with 1 nonprimary partner. Drug and alcohol use were significantly associated with unprotected anal sex. CONCLUSIONS Our findings support the continued need for effective intervention strategies for MSM that address relationship status, serostatus of partners, and drug and alcohol use.

Effects of a behavioural intervention to reduce acquisition of HIV infection among men who have sex with men: the EXPLORE randomised controlled study.

BACKGROUND Effective interventions are needed to prevent acquisition of HIV infection in men who have sex with men. To date, no behavioural interventions specifically for this risk group have been tested with HIV infection as the primary outcome. METHODS This multisite two-group randomised controlled phase IIb trial tested the efficacy of a behavioural intervention in preventing HIV infection among 4295 men who have sex with men. The experimental intervention consisted of ten one-on-one counselling sessions followed by maintenance sessions every 3 months. The standard condition was twice-yearly Project RESPECT individual counselling. Twice-yearly follow-up visits included testing for HIV antibody and assessment of behavioural outcomes. FINDINGS The rate of acquisition of HIV infection was 18.2% (95% CI -4.7 to 36.0) lower in the intervention group than the standard group. Adjustment for baseline covariates attenuated the intervention effect to 15.7% (-8.4 to 34.4). The effect was more favourable in the first 12-18 months of follow-up. The occurrence of unprotected receptive anal intercourse with HIV-positive and unknown-status partners was 20.5% (10.9 to 29.0) lower in the intervention than in the standard group. INTERPRETATION The results from the primary analyses allow us to rule out that the experimental intervention is associated with a 35% lower rate of HIV acquisition than in the standard group. The overall estimate of a difference of 18.2%, more favourable estimates of effect in the first 12-18 months, and similar effects on risk behaviours suggest that prevention of HIV infection among men who have sex with men by a behavioural intervention is feasible. Further work should be done to develop more effective interventions.

Associations of Race/Ethnicity With HIV Prevalence and HIV-Related Behaviors Among Young Men Who Have Sex With Men in 7 Urban Centers in the United States

Abstract:Using data from a multisite venue-based survey of male subjects aged 15 to 22 years, we examined racial/ethnic differences in demographics, partner type, partner type-specific condom use, drug use, and HIV prevalence in 3316 US black, multiethnic black, Latino, and white men who have sex with men (MSM). We further estimated associations of these factors with HIV infection and their influence on racial/ethnic disparities in HIV prevalence. HIV prevalences were 16% for both black and multiethnic black participants, 6.9% for Latinos, and 3.3% for whites. Paradoxically, potentially risky sex and drug-using behaviors were generally reported most frequently by whites and least frequently by blacks. In a multiple logistic regression analysis, positive associations with HIV included older age, being out of school or work, sex while on crack cocaine, and anal sex with another male regardless of reported condom use level. Differences in these factors did not explain the racial/ethnic disparities in HIV prevalence, with both groups of blacks experiencing more than 9 times and Latinos experiencing approximately twice the fully adjusted odds of infection compared with whites. Understanding racial/ethnic disparities in HIV risk requires information beyond the traditional risk behavior and partnership type distinctions. Prevention programs should address risks in steady partnerships, target young men before sexual initiation with male partners, and tailor interventions to men of color and of lower socioeconomic status.

Age-Specific Prevalence of Anal Human Papillomavirus Infection in HIV-Negative Sexually Active Men Who Have Sex with Men: The EXPLORE Study

BACKGROUND In the United States, anal cancer in men who have sex with men (MSM) is more common than cervical cancer in women. Human papillomavirus (HPV) is causally linked to the development of anal and cervical cancer. In women, cervical HPV infection peaks early and decreases after the age of 30. Little is known about the age-specific prevalence of anal HPV infection in human immunodeficiency virus (HIV)-negative MSM. METHODS We studied the prevalence and determinants of anal HPV infection in 1218 HIV-negative MSM, 18-89 years old, who were recruited from 4 US cities. We assessed anal HPV infection status by polymerase chain reaction. RESULTS HPV DNA was found in the anal canal of 57% of study participants. The prevalence of anal HPV infection did not change with age or geographic location. Anal HPV infection was independently associated with receptive anal intercourse (odds ratio [OR], 2.0; P<.0001) during the preceding 6 months and with >5 sex partners during the preceding 6 months (OR, 1.5; P<.0001). CONCLUSIONS Urban, HIV-negative MSM have a stable, high prevalence of anal HPV infection across all age groups. These results differ substantially from the epidemiologic profile of cervical HPV infection in women. This may reflect differences between these populations with respect to the number of new sex partners after the age of 30 and may explain the high incidence of anal cancer in MSM.

Unrecognized HIV infection, risk behaviors, and perceptions of risk among young men who have sex with men: opportunities for advancing HIV prevention in the third decade of HIV/AIDS.

This study evaluated the magnitude and distribution of unrecognized HIV infection among young men who have sex with men (MSM) and of those with unrecognized infection, the prevalence and correlates of unprotected anal intercourse (UAI), perceived low risk for infection, and delayed HIV testing. MSM aged 15-29 years were approached, interviewed, counseled, and tested for HIV at 263 randomly sampled venues in 6 US cities from 1994-2000. Of 5649 MSM participants, 573 (10%) tested positive for HIV. Of these, 91% of black, 69% of Hispanic, and 60% of white MSM (77% overall) were unaware of their infection. The 439 MSM with unrecognized infection reported a total of 2253 male sex partners in the previous 6 months; 51% had UAI; 59% perceived that they were at low risk for being infected; and 55% had not tested in the previous year. The HIV epidemic among MSM in the United States continues unabated, in part, because many young HIV-infected MSM are unaware of their infection and unknowingly expose their partners to HIV. To advance HIV prevention in the third decade of HIV/AIDS, prevention programs must reduce unrecognized infection among young MSM by increasing the demand for and availability of HIV testing services.

Longitudinal patterns of methamphetamine, popper (amyl nitrite), and cocaine use and high-risk sexual behavior among a cohort of san francisco men who have sex with men.

Most prior studies examining drug use among men who have sex with men (MSM) have been cross-sectional or retrospective and have not determined whether periods of increased drug use are associated with high-risk sexual behavior at the individual level. In this article, we describe patterns of use of methamphetamines, poppers, and sniffed cocaine and sexual risk behavior among 736 San Francisco MSM enrolled in the EXPLORE study and followed for up to 48 months. In longitudinal analysis, use of methamphetamines, poppers, and sniffed cocaine declined during follow-up. However, compared with older participants, younger participants were more likely to increase their drug use over time. Results of conditional logistic regression demonstrated that high-risk sexual behavior was more common during reporting periods characterized by increased methamphetamine, poppers, or sniffed cocaine use. This within-person analysis found that compared with periods of no drug use, periods of both light drug use (less than weekly use of drugs) and heavier drug use (at least weekly use of at least one drug) were significantly associated with increased risk of engaging in uprotected anal sex with an HIV-positive or unknown-status partner. These results suggest that even intermittent, recreational use of these drugs may lead to high-risk sexual behavior, and that, to reduce and prevent risks of HIV, no level of use of these drugs should be considered “safe.” HIV prevention interventions should target MSM who report either light or heavy use of methamphetamines, poppers, and sniffed cocaine.

Sexual risk, nitrite inhalant use, and lack of circumcision associated with HIV seroconversion in men who have sex with men in the united states

Men who have sex with men (MSM) continue to account for the largest number of new HIV infections in the United States, but limited data exist on independent risk factors for infection beyond the early 1990s. The HIV Network for Prevention Trials Vaccine Preparedness Study enrolled 3257 MSM in 6 US cities from 1995 to 1997. HIV seroincidence was 1.55 per 100 person-years (95% confidence interval: 1.23-1.95) over 18 months of follow-up. On multi-variable analysis using time-dependent covariates, independent risk factors for HIV seroconversion were increased number of reported HIV-negative male sex partners (adjusted odds ratio (AOR) = 1.14 per partner, population attributable risk (PAR) = 28%), nitrite inhalant use (AOR = 2.2, PAR = 28%), unprotected receptive anal sex with an HIV unknown serostatus partner (AOR = 2.7, PAR = 15%) or HIV-positive partner (AOR = 3.4, PAR = 12%), protected receptive anal sex with an HIV-positive partner (AOR = 2.2, PAR = 11%), lack of circumcision (AOR = 2.0, PAR = 10%), and receptive oral sex to ejaculation with an HIV-positive partner (AOR = 3.8, PAR = 7%). Having a large number of male sex partners, nitrite inhalant use, and engaging in receptive anal sex explained the majority of infections in this cohort and should be targeted in prevention strategies for MSM.