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

Cross-reactive T cell responses in HIV CRF01_AE and B'-infected intravenous drug users: implications for superinfection and vaccines.

Abstract We previously observed limited cross-reactive T cell responses in two HIV-1-superinfected injection drug users (IDUs) before superinfection [Ramos A, et al.: J Virol 2002;76(15):7444-7452]. To elucidate the role of such responses in superinfection we examined cross-reactive T cell responses in IDUs infected with a single HIV-1 subtype. In this study, IFN-gamma ELISPOT assays were performed using recombinant vaccinia constructs and peripheral blood mononuclear cells (PBMCs) from 43 IDUs singly infected with CRF01_AE or B' from the same cohort as the superinfected IDUs. PBMCs were from time points corresponding to pre- (early) or post- (late) superinfection in the superinfected IDUs. We observed that most singly infected IDUs had cross-reactivity in samples from early (84% of CRF01_AE and 78% of B'-infected IDUs) and late (96% of CRF_01AE and 77% of B'-infected IDUs) time points. Frequent homologous reactivity at early (67% of CRF-01AE and 100% of B') and late (84% of CRF01_AE-infected and 100% of B'-infected IDUs) time points was also observed. Cross-reactive responses were predominantly to Pol and were broader and higher in CRF01_AE than in B'-infected IDUs (medians of 825 vs. 90 and 585 vs. 60 spot-forming units/10(6) PBMCs at early and late time points, respectively). Our results show that cross-reactive responses were more prevalent with greater height and breadth in singly infected IDUs than previously observed in corresponding collection time points of superinfected IDU. Thus, low or absent cross-reactivity may have contributed to the previously observed superinfections. These data are relevant for understanding superinfection and improving vaccine design

Risk behaviors and risk factors for HIV infection among participants in the Bangkok tenofovir study, an HIV pre-exposure prophylaxis trial among people who inject drugs.

INTRODUCTION: HIV spread rapidly among people who inject drugs in Bangkok in the late 1980s. In recent years, changes in drug use and HIV-associated risk behaviors have been reported. We examined data from the Bangkok Tenofovir Study, an HIV pre-exposure prophylaxis trial conducted among people who inject drugs, to assess participant risk behavior and drug use, and to identify risk factors for HIV infection. METHODS: The Bangkok Tenofovir Study was a randomized, double-blind, placebo-controlled trial. HIV status was assessed monthly and risk behavior every 3 months. We used generalized estimating equations logistic regression to model trends of injecting, needle sharing, drugs injected, incarceration, and sexual activity reported at follow-up visits; and proportional hazards models to evaluate demographic characteristics, sexual activities, incarceration, drug injection practices, and drugs injected during follow-up as predictors of HIV infection. RESULTS: The proportion of participants injecting drugs, sharing needles, and reporting sex with more than one partner declined during follow-up (p<0.001). Among participants who reported injecting at enrollment, 801 (53.2%) injected methamphetamine, 559 (37.1%) midazolam, and 527 (35.0%) heroin. In multivariable analysis, young age (i.e., 20-29 years) (p = 0.02), sharing needles (p<0.001), and incarceration in prison (p = 0.002) were associated with incident HIV infection. Participants reporting sex with an opposite sex partner, live-in partner, casual partner, or men reporting sex with male partners were not at a significantly higher risk of HIV infection compared to those who did not report these behaviors. CONCLUSION: Reports of HIV-associated risk behavior declined significantly during the trial. Young age, needle sharing, and incarceration were independently associated with HIV infection. Sexual activity was not associated with HIV infection, suggesting that the reduction in HIV incidence among participants taking daily oral tenofovir compared to those taking placebo was due to a decrease in parenteral HIV transmission

Assessment of Oral Fluid HIV Test Performance in an HIV Pre-Exposure Prophylaxis Trial in Bangkok, Thailand.

Rapid easy-to-use HIV tests offer opportunities to increase HIV testing among populations at risk of infection. We used the OraQuick Rapid HIV-1/2 antibody test (OraQuick) in the Bangkok Tenofovir Study, an HIV pre-exposure prophylaxis trial among people who inject drugs.The Bangkok Tenofovir Study was a randomized, double-blind, placebo-controlled trial. We tested participants' oral fluid for HIV using OraQuick monthly and blood using a nucleic-acid amplification test (NAAT) every 3 months. We used Kaplan-Meier methods to estimate the duration from a positive HIV NAAT until the mid-point between the last non-reactive and first reactive oral fluid test and proportional hazards to examine factors associated with the time until the test was reactive.We screened 3678 people for HIV using OraQuick. Among 447 with reactive results, 436 (97.5%) were confirmed HIV-infected, 10 (2.2%) HIV-uninfected, and one (0.2%) had indeterminate results. Two participants with non-reactive OraQuick results were, in fact, HIV-infected at screening yielding 99.5% sensitivity, 99.7% specificity, a 97.8% positive predictive value, and a 99.9% negative predictive value. Participants receiving tenofovir took longer to develop a reactive OraQuick (191.8 days) than participants receiving placebo (16.8 days) (p = 0.02) and participants infected with HIV CRF01_AE developed a reactive OraQuick earlier than participants infected with other subtypes (p = 0.04).The oral fluid HIV test performed well at screening, suggesting it can be used when rapid results and non-invasive tools are preferred. However, participants receiving tenofovir took longer to develop a reactive oral fluid test result than those receiving placebo. Thus, among people using pre-exposure prophylaxis, a blood-based HIV test may be an appropriate choice.ClinicalTrials.gov NCT00119106

Kaplan-Meier estimates of time (28 day months) from date HIV was detected using nucleic acid amplification until the mid-point date between the last non-reactive and first reactive oral fluid HIV test.

<p>(A) By study drug group: tenofovir or placebo. (B) Controlling for study drug group, by HIV subtype: CRF01_AE or other subtypes.</p

HIV test results of participants in the Bangkok Tenofovir Study, 2005–2012.

<p>OraQuick, OraQuick Rapid HIV-1/2 Antibody Test; EIA, enzyme immune assay; NAAT, nucleic-acid amplification test. ^aTwo participants with reactive OraQuick tests during follow-up were later found to have been HIV-infected before enrollment. ^bPlasma collected at 3-monthly visits from participants with a non-reactive OraQuick test result was tested for HIV using EIA.</p