MTN-003B

Primary Objective

• Compare changes in Bone Mineral Density (BMD) after one year among VOICE participants receiving oral tenofovir disoproxil fumarate (tenofovir or TDF) and emtricitabine (FTC)/TDF (Truvada) compared with oral placebo

Study Summary
The BMD Substudy was an observational substudy of VOICE designed to assess the impact of oral TDF and oral FTC/TDF on bone mineral density. VOICE participants randomized to oral study product at MTN-003B study sites were offered participation in the BMD Substudy. Scheduled follow-up, including nutritional assessment, DXA scan, and blood tests related to bone turnover and metabolism, occurred on a semi-annual basis during VOICE study participation, at the scheduled end of product use visit, and at 6 and 12 months following the discontinuation of an oral study product in VOICE. A secondary objective was to provide a description of changes over time in nutritional assessment components among eligible VOICE participants. Exploratory objectives included the examination of potential mechanisms of BMD changes among eligible VOICE participants, as well as changes in urinary phosphorous excretion in relation to possible changes in bone density. The potential impact of tenofovir-containing prevention agents on the bone density of healthy women of reproductive age, who may be exposed to other possible stressors on bone health, is important for the evaluation of the overall safety of these agents for prevention of HIV infection in women.

MTN-003B completed follow-up on July 29, 2013. Primary study results were presented at the HIV Research for Prevention (HIV R4P) meeting held on October 28-31, 2014, in Cape Town, South Africa. The primary manuscript was published in the Journal of Acquired Immune Deficiency Syndromes in March 2016. A total of two papers have been published from this study.

Primary Results
Small but significant reversible decreases in BMD were observed among young African women with higher adherence on TDF-based oral PrEP. Observed differences were in the range seen in prior studies of HIV-negative men and women. Of 518 women enrolled, 432 had dual-energy x-ray absorptiometry results at baseline and week 48. In the primary analysis, no significant differences in percent BMD change in hip or spine between arms observed, likely because of low product adherence. Among the subset with tenofovir detection in 75%–100% of plasma samples, the mean percent BMD change from baseline to week 48 in the LS was 1.4% lower for TDF or emtricitabine/TDF recipients than for placebo (P = 0.002) and TH BMD was 0.9% lower (P = 0.018). BMD changes from end of active treatment to 48 weeks were significantly greater in the active arm participants compared with placebo participants with a net difference of approximately +0.9% at the LS (P = 0.007) and +0.7% (P = 0.003) at the TH.