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

Scatterplots of PBMC TFV-DP concentration versus plasma TFV concentration (2a), PBMC TFV-DP concentration versus hair TFV concentration (2b) and plasma TFV concentration versus hair TFV concentration (2c).

<p>Scatterplots of PBMC TFV-DP concentration versus plasma TFV concentration (2a), PBMC TFV-DP concentration versus hair TFV concentration (2b) and plasma TFV concentration versus hair TFV concentration (2c).</p

Baseline characteristics of participants in the active and placebo participant arms of the US CDC PrEP safety study.

<p>Baseline characteristics of participants in the active and placebo participant arms of the US CDC PrEP safety study.</p

Detection of tenofovir in hair, plasma and peripheral blood mononuclear cells in active and placebo participant arms in the US CDC PrEP safety study.

<p>Detection of tenofovir in hair, plasma and peripheral blood mononuclear cells in active and placebo participant arms in the US CDC PrEP safety study.</p

Percent differences in tenofovir in hair, plasma and peripheral blood mononuclear cells in active arm participants, by linear regression (univariate and multivariable results presented), in the US CDC PrEP safety study.

<p>Percent differences in tenofovir in hair, plasma and peripheral blood mononuclear cells in active arm participants, by linear regression (univariate and multivariable results presented), in the US CDC PrEP safety study.</p

Scatterplots of PBMC TFV-DP concentration versus plasma TFV concentration (2a), PBMC TFV-DP concentration versus hair TFV concentration (2b) and plasma TFV concentration versus hair TFV concentration (2c).

<p>Scatterplots of PBMC TFV-DP concentration versus plasma TFV concentration (2a), PBMC TFV-DP concentration versus hair TFV concentration (2b) and plasma TFV concentration versus hair TFV concentration (2c).</p

Study design and participant disposition.

<p>Study design and participant disposition.</p

“Research participants want to feel they are better off than they were before research was introduced to them”: engaging cameroonian rural plantation populations in HIV research

<p>Abstract</p> <p>Background</p> <p>During a period of evolving international consensus on how to engage communities in research, facilitators and barriers to participation in HIV prevention research were explored in a rural plantation community in the coastal region of Cameroon.</p> <p>Methods</p> <p>A formative rapid assessment using structured observations, focus group discussions (FGD), and key informant interviews (KIIs) was conducted with a purposive non-probabilistic sample of plantation workers and their household members. Eligibility criteria included living or working >1 year within the plantation community and age >18 years. Both rapid and in-depth techniques were used to complete thematic analysis.</p> <p>Results</p> <p>Sixty-five persons participated in the study (6 FGDs and 12 KIIs). Participants viewed malaria and gastrointestinal conditions as more common health concerns than HIV. They identified three factors as contributing to HIV risk: concurrent sexual relationships, sex work, and infrequent condom use. Interviewees perceived that the community would participate in HIV research if it is designed to: (1) improve community welfare, (2) provide comprehensive health services and treatment for illnesses, (3) protect the personal information of participants, especially those who test positive for HIV, (4) provide participant incentives, (5) incorporate community input, and (6) minimize disruptions to “everyday life”. Barriers to participation included: (1) fear of HIV testing, (2) mistrust of researchers given possible disrespect or intolerance of plantation community life and lack of concern for communication, (3) time commitment demands, (3) medical care and treatment that would be difficult or costly to access, and (4) life disruptions along with potential requirements for changes in behaviour (i.e., engage in or abstain from alcohol use and sex activities).</p> <p>Conclusions</p> <p>Consistent with UNAIDS guidelines for good participatory practice in HIV prevention research, study participants placed a high premium on researchers’ politeness, trust, respect, communication, tolerance and empathy towards their community. Plantation community members viewed provision of comprehensive health services as an important community benefit likely to enhance HIV research participation.</p

Comparing pharmacologic measures of tenofovir exposure in a U.S. pre-exposure prophylaxis randomized trial

<div><p>It is critical to assess adherence to pre-exposure prophylaxis (PrEP) in clinical trials. The relationship between pharmacokinetic measures of PrEP adherence and other adherence measures used in PrEP trials requires further characterization. Plasma, peripheral blood mononuclear cells (PBMCs), and hair samples were collected from 88 HIV-uninfected men who have sex with men in a placebo-controlled randomized PrEP trial; announced pill counts, medication electronic monitoring (MEMS), and self-report using visual analog scale (VAS) were also collected. Tenofovir (TFV or TFV-DP) in plasma, hair, and PBMCs were quantified. Proportions with drug detection, Spearman correlation coefficients, and univariate and multivariable regression models were used. Drug detection in plasma, PBMC, and hair samples was highly concordant with treatment arm assignment. TFV or TFV-DP levels were detected in most active-arm participants: 44/47 (94%) in plasma, 46/47 (98%) in hair, and 44/47 (94%) in PBMCs and in only 1/41 placebo arm participant. Correlation coefficients were r = 0.59 for plasma and PBMC, r = 0.34 for PBMC and hair and r = 0.36 for plasma and hair. MEMS and announced pill-counts were moderately correlated (r = 0.52) but less so with pharmacologic measures (range of r = 0.12 to 0.38). Self-reported adherence by visual analog scale demonstrated essentially no correlation with drug levels (r = 0.06 for hair, PBMC or plasma) and was a poor indicator of exposure to study product. Indices of drug exposure are important indicators in assessing adherence to PrEP; accounting for variability between measures may improve interpretation and use of adherence measures in future PrEP studies.</p><p>Clinical trial registration</p><p>Clinical Trials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT00131677" target="_blank">NCT00131677</a></p></div