A phase 1 randomized, open label, rectal safety, acceptability, pharmacokinetic, and pharmacodynamic study of three formulations of tenofovir 1% Gel (the CHARM-01 study)

Objectives: The CHARM-01 study characterized the safety, acceptability, pharmacokinetics (PK), and pharmacodynamics (PD) of three tenofovir (TFV) gels for rectal application. The vaginal formulation (VF) gel was previously used in the CAPRISA 004 and VOICE vaginal microbicide Phase 2B trials and the RMP-02/MTN-006 Phase 1 rectal safety study. The reduced glycerin VF (RGVF) gel was used in the MTN-007 Phase 1 rectal microbicide trial and is currently being evaluated in the MTN-017 Phase 2 rectal microbicide trial. A third rectal specific formulation (RF) gel was also evaluated in the CHARM-01 study. Methods: Participants received 4 mL of the three TFV gels in a blinded, crossover design: seven daily doses of RGVF, seven daily doses of RF, and six daily doses of placebo followed by one dose of VF, in a randomized sequence. Safety, acceptability, compartmental PK, and explant PD were monitored throughout the trial. Results: All three gels were found to be safe and acceptable. RF and RGVF PK were not significantly different. Median mucosal mononuclear cell (MMC) TFV-DP trended toward higher values for RF compared to RGVF (1136 and 320 fmol/106 cells respectively). Use of each gel in vivo was associated with significant inhibition of ex vivo colorectal tissue HIV infection. There was also a significant negative correlation between the tissue levels of TFV, tissue TFV-DP, MMC TFV-DP, rectal fluid TFV, and explant HIV-1 infection. Conclusions: All three formulations were found to be safe and acceptable. However, the safety profile of the VF gel was only based on exposure to one dose whereas participants received seven doses of the RGVF and RF gels. There was a trend towards higher tissue MMC levels of TFV-DP associated with use of the RF gel. Use of all gels was associated with significant inhibition of ex vivo tissue HIV infection. Trial Registration: ClinicalTrials.gov NCT01575405

Failure to Identify HIV-Infected Individuals in a Clinical Trial Using a Single HIV Rapid Test for Screening

BACKGROUND: In the HIV Prevention Trials Network (HPTN) 061 study, 8 (2.3%) of 348 HIV-infected participants identified as HIV uninfected at study enrollment using a single HIV rapid test for screening were found to be HIV infected after additional testing. OBJECTIVES: To evaluate the performance of different HIV assays for detection of HIV infection in HPTN 061 participants with missed infection and individuals with viral suppression. METHODS: Plasma samples from 8 HPTN 061 participants, 17 elite controllers, and 101 individuals on antiretroviral treatment (ART) were tested for HIV with 3 rapid tests, 2 laboratory-based immunoassays, and a Western blot assay. The HPTN 061 samples were also tested with 2 HIV RNA assays and an antiretroviral drug assay. RESULTS: Of the 8 HPTN 061 participants with missed infection, 1 was an elite controller, 1 was taking ART, 2 were missed because of testing or clerical errors, 1 had recent HIV infection (identified using a multi-assay algorithm), and 3 had acute HIV infection. Two (1.7%) of 118 individuals with viral suppression (both taking ART) had at least 1 false-negative test. CONCLUSIONS: In clinical trials, HIV infections can be missed for a variety of reasons. Using more than one assay to screen for HIV infection may reduce the number of missed infections

HIV and STIs Among MSM in Tajikistan: Laboratory-Confirmed Diagnoses and Self-Reported Testing Behaviors

Little is known about the prevalence and associations of HIV/STI diagnoses and testing behaviors among men who have sex with men (MSM) in Tajikistan. A non-governmental organization conducted a cross-sectional study of MSM (n = 502) assessing laboratory-confirmed HIV/STI diagnoses, HIV/STI testing behavior in the past 6 months, sociodemographics, HIV/STI risk factors, and victimization/discrimination. Overall, 2.6 % were diagnosed with HIV, 2.2 % with syphilis, 17.6 % with chlamydia, and 56.0 % with herpes. Recent testing rates were low for HIV (35.9 %) and STIs (14.1 %). Compared to MSM who completed university, MSM with a high school education or less had lower odds of recent HIV and STI testing; however, victimization and healthcare discrimination were associated with greater odds of recent STI testing. Given the low HIV prevalence, there is a window of opportunity to extinguish the epidemic before it worsens. Non-governmental organizations are indispensable for expanding testing strategies because they can efficiently reach MSM in Tajikistan

Predictors of Daily Adherence to HIV Pre-exposure Prophylaxis in Gay/Bisexual Men in the PRELUDE Demonstration Project

Adequate adherence to pre-exposure prophylaxis (PrEP) is critical to prevent HIV infection, but accurately measuring adherence remains challenging. We compared two biological [blood drug concentrations in plasma and peripheral blood mononuclear cells (PBMC)] and two self-reported measures (facilitated recall to clinicians and self-report in online surveys) and identified predictors of daily PrEP adherence among gay and bisexual men (GBM) in their first 12 months on PRELUDE, an open-label, single-arm PrEP demonstration project in New South Wales, Australia. 327 participants were enrolled; 263 GBM attended their 12-month follow-up visit (81% retention). Overall, 91% of blood samples had plasma drug concentrations indicative of taking 7 pills/week, and 99% had protective drug concentrations (≥ 4 pills/week). Facilitated recall to clinicians identified 99% of participants with protective adherence as measured by PBMC drug concentrations. Daily adherence measured by facilitated recall was associated with behavioural practices including group sex (aOR 1.33, 95% CI 1.15–1.53, p < 0.001). Retained participants maintained high adherence to daily PrEP over 12 months, confirmed by four different measures. Facilitated recall to clinicians is a suitable measure for assessing PrEP adherence in populations engaged in care where there is established trust and rapport with patients. Trial registration: ClinicalTrials.gov NCT02206555