HIV Prevalence, Risks for HIV Infection, and Human Rights among Men Who Have Sex with Men (MSM) in Malawi, Namibia, and Botswana

BACKGROUND: In the generalized epidemics of HIV in southern Sub-Saharan Africa, men who have sex with men have been largely excluded from HIV surveillance and research. Epidemiologic data for MSM in southern Africa are among the sparsest globally, and HIV risk among these men has yet to be characterized in the majority of countries. METHODOLOGY: A cross-sectional anonymous probe of 537 men recruited with non-probability sampling among men who reported ever having had sex with another man in Malawi, Namibia, and Botswana using a structured survey instrument and HIV screening with the OraQuick(c) rapid test kit. PRINCIPAL FINDINGS: The HIV prevalence among those between the ages of 18 and 23 was 8.3% (20/241); 20.0% (42/210) among those 24-29; and 35.7% (30/84) among those older than 30 for an overall prevalence of 17.4% (95% CI 14.4-20.8). In multivariate logistic regressions, being older than 25 (aOR 4.0, 95% CI 2.0-8.0), and not always wearing condoms during sex (aOR 2.6, 95% CI 1.3-4.9) were significantly associated with being HIV-positive. Sexual concurrency was common with 16.6% having ongoing concurrent stable relationships with a man and a woman and 53.7% had both male and female sexual partners in proceeding 6 months. Unprotected anal intercourse was common and the use of petroleum-based lubricants was also common when using condoms. Human rights abuses, including blackmail and denial of housing and health care was prevalent with 42.1% (222/527) reporting at least one abuse. CONCLUSIONS: MSM are a high-risk group for HIV infection and human rights abuses in Malawi, Namibia, and Botswana. Concurrency of sexual partnerships with partners of both genders may play important roles in HIV spread in these populations. Further epidemiologic and evaluative research is needed to assess the contribution of MSM to southern Africa's HIV epidemics and how best to mitigate this. These countries should initiate and adequately fund evidence-based and targeted HIV prevention programs for MSM

Bone Mineral Density in HIV-Negative Men Participating in a Tenofovir Pre-Exposure Prophylaxis Randomized Clinical Trial in San Francisco

Pre-exposure prophylaxis (PrEP) trials are evaluating regimens containing tenofovir-disoproxil fumarate (TDF) for HIV prevention. We determined the baseline prevalence of low bone mineral density (BMD) and the effect of TDF on BMD in men who have sex with men (MSM) in a PrEP trial in San Francisco.We evaluated 1) the prevalence of low BMD using Dual Energy X-ray Absorptiometry (DEXA) in a baseline cohort of 210 HIV-uninfected MSM who screened for a randomized clinical trial of daily TDF vs. placebo, and 2) the effects of TDF on BMD in a longitudinal cohort of 184 enrolled men. Half began study drug after a 9-month delay to evaluate changes in risk behavior associated with pill-use. At baseline, 20 participants (10%) had low BMD (Z score≤-2.0 at the L2-L4 spine, total hip, or femoral neck). Low BMD was associated with amphetamine (OR = 5.86, 95% CI 1.70-20.20) and inhalant (OR = 4.57, 95% CI 1.32-15.81) use; men taking multivitamins, calcium, or vitamin D were less likely to have low BMD at baseline (OR = 0.26, 95% CI 0.10-0.71). In the longitudinal analysis, there was a 1.1% net decrease in mean BMD in the TDF vs. the pre-treatment/placebo group at the femoral neck (95% CI 0.4-1.9%), 0.8% net decline at the total hip (95% CI 0.3-1.3%), and 0.7% at the L2-L4 spine (95% CI -0.1-1.5%). At 24 months, 13% vs. 6% of participants experienced >5% BMD loss at the femoral neck in the TDF vs. placebo groups (p = 0.13).Ten percent of HIV-negative MSM had low BMD at baseline. TDF use resulted in a small but statistically significant decline in BMD at the total hip and femoral neck. Larger studies with longer follow-up are needed to determine the trajectory of BMD changes and any association with clinical fractures.ClinicalTrials.gov: NCT00131677

Challenges of diagnosing acute HIV-1 subtype C infection in African women: performance of a clinical algorithm and the need for point-of-care nucleic-acid based testing.

Background. Prompt diagnosis of acute HIV infection (AHI) benefits the individual and provides opportunities for public health intervention. The aim of this study was to describe most common signs and symptoms of AHI, correlate these with early disease progression and develop a clinical algorithm to identify acute HIV cases in resource limited setting. Methods. 245 South African women at high-risk of HIV-1 were assessed for AHI and received monthly HIV-1 antibody and RNA testing. Signs and symptoms at first HIV-positive visit were compared to HIV-negative visits. Logistic regression identified clinical predictors of AHI. A model-based score was assigned to each predictor to create a risk score for every woman. Results. Twenty-eight women seroconverted after a total of 390 person-years of follow-up with an HIV incidence of 7.2/100 person-years (95%CI 4.5–9.8). Fifty-seven percent reported ≥1 sign or symptom at the AHI visit. Factors predictive of AHI included age <25 years (OR = 3.2; 1.4–7.1), rash (OR = 6.1; 2.4–15.4), sore throat (OR = 2.7; 1.0–7.6), weight loss (OR = 4.4; 1.5–13.4), genital ulcers (OR = 8.0; 1.6–39.5) and vaginal discharge (OR = 5.4; 1.6–18.4). A risk score of 2 correctly predicted AHI in 50.0% of cases. The number of signs and symptoms correlated with higher HIV-1 RNA at diagnosis (r = 0.63; p<0.001). Conclusions. Accurate recognition of signs and symptoms of AHI is critical for early diagnosis of HIV infection. Our algorithm may assist in risk-stratifying individuals for AHI, especially in resource-limited settings where there is no routine testing for AHI. Independent validation of the algorithm on another cohort is needed to assess its utility further. Point-of-care antigen or viral load technology is required, however, to detect asymptomatic, antibody negative cases enabling early interventions and prevention of transmission

Screening for genital and anorectal sexually transmitted infections in HIV prevention trials in Africa.

OBJECTIVES: To demonstrate the value of routine, basic sexually transmitted infection (STI) screening at enrolment into an HIV-1 vaccine feasibility cohort study and to highlight the importance of soliciting a history of receptive anal intercourse (RAI) in adults identified as "high risk". METHODS: Routine STI screening was offered to adults at high risk of HIV-1 upon enrolment into a cohort study in preparation for HIV-1 vaccine trials. Risk behaviours and STI prevalence were summarised and the value of microscopy assessed. Associations between prevalent HIV-1 infection and RAI or prevalent STI were evaluated with multiple logistic regression. RESULTS: Participants had a high burden of untreated STI. Symptom-directed management would have missed 67% of urethritis cases in men and 59% of cervicitis cases in women. RAI was reported by 36% of male and 18% of female participants. RAI was strongly associated with HIV-1 in men (adjusted odds ratio (aOR) 3.8; 95% CI 2.0 to 6.9) and independently associated with syphilis in women (aOR 12.9; 95% CI 3.4 to 48.7). CONCLUSIONS: High-risk adults recruited for HIV-1 prevention trials carry a high STI burden. Symptom-directed treatment may miss many cases and simple laboratory-based screening can be done with little cost. Risk assessment should include questions about anal intercourse and whether condoms were used. STI screening, including specific assessment for anorectal disease, should be offered in African research settings recruiting participants at high risk of HIV-1 acquisition

Longitudinal dynamics of the HIV-specific B cell response during intermittent treatment of primary HIV infection

BACKGROUND: Neutralizing antibodies develop in natural HIV-1 infection. Their development often takes several years and may rely on chronic virus exposure. At the same time recent studies show that treatment early in infection may provide opportunities for immune preservation. However, it is unknown how intermittent treatment in early infection affects development of the humoral immune response over time. We investigate the effect of cART in early HIV infection on the properties of the memory B cell compartment following 6 months of cART or in the absence of treatment. The patients included participated in the Primo-SHM trial where patients with an early HIV-1 infection were randomized to no treatment or treatment for 24 or 60 weeks. METHODS: Primo-SHM trial patients selected for the present study were untreated (n = 23) or treated for 24 weeks (n = 24). Here we investigate memory B cell properties at viral set-point and at a late time point (respectively median 54 and 73 weeks) before (re)-initiation of treatment. RESULTS: At viral set-point, the memory B cell compartment in treated patients demonstrated significantly lower fractions of antigen-primed, activated, memory B cells (p = 0.006). In contrast to untreated patients, in treated patients the humoral HIV-specific response reached a set point over time. At a transcriptional level, sets of genes that showed enhanced expression in memory B cells at viral setpoint in untreated patients, conversely showed rapid increase of expression of the same genes in treated patients at the late time point. CONCLUSION: These data suggest that, although the memory B cell compartment is phenotypically preserved until viral setpoint after treatment interruption, the development of the HIV-specific antibody response may benefit from exposure to HIV. The effect of viral exposure on B cell properties is also reflected by longitudinal changes in transcriptional profile in memory B cells over time in early treated patients

No Treatment versus 24 or 60 Weeks of Antiretroviral Treatment during Primary HIV Infection: The Randomized Primo-SHM Trial

Background: The objective of this study was to assess the benefit of temporary combination antiretroviral therapy (cART) during primary HIV infection (PHI). Methods and Findings: Adult patients with laboratory evidence of PHI were recruited in 13 HIV treatment centers in the Netherlands and randomly assigned to receive no treatment or 24 or 60 wk of cART (allocation in a 1:1:1 ratio); if therapy was clinically indicated, participants were randomized over the two treatment arms (allocation in a 1:1 ratio). Primary end points were (1) viral set point, defined as the plasma viral load 36 wk after randomization in the no treatment arm and 36 wk after tr Conclusions: In this trial, temporary cART during PHI was found to transiently lower the viral set point and defer the restart of cART during chronic HIV infection