Bone Mineral Density Changes among HIV-Uninfected Young Adults in a Randomised Trial of Pre-Exposure Prophylaxis with Tenofovir-Emtricitabine or Placebo in Botswana

<div><p>Background</p><p>Tenofovir-emtricitabine (TDF-FTC) pre-exposure prophylaxis (PrEP) has been found to be effective for prevention of HIV infection in several clinical trials. Two studies of TDF PrEP among men who have sex with men showed slight bone mineral density (BMD) loss. We investigated the effect of TDF and the interaction of TDF and hormonal contraception on BMD among HIV-uninfected African men and women.</p><p>Method</p><p>We evaluated the effects on BMD of using daily oral TDF-FTC compared to placebo among heterosexual men and women aged 18–29 years enrolled in the Botswana TDF2 PrEP study. Participants had BMD measurements at baseline and thereafter at 6-month intervals with dual-energy X-ray absorptiometry (DXA) scans at the hip, spine, and forearm.</p><p>Results</p><p>A total of 220 participants (108 TDF-FTC, 112 placebo) had baseline DXA BMD measurements at three anatomic sites. Fifteen (6.8%) participants had low baseline BMD (z-score of <−2.0 at any anatomic site), including 3/114 women (2.6%) and 12/106 men (11.3%) (p = 0.02). Low baseline BMD was associated with being underweight (p = 0.02), having high blood urea nitrogen (p = 0.02) or high alkaline phosphatase (p = 0.03), and low creatinine clearance (p = 0.04). BMD losses of >3.0% at any anatomic site at any time after baseline were significantly greater for the TDF-FTC treatment group [34/68 (50.0%) TDF-FTC vs. 26/79 (32.9%) placebo; p = 0.04]. There was a small but significant difference in the mean percent change in BMD from baseline for TDF-FTC versus placebo at all three sites at month 30 [forearm −0.84% (p = 0.01), spine −1.62% (p = 0.0002), hip −1.51% (p = 0.003)].</p><p>Conclusion</p><p>Use of TDF-FTC was associated with a small but statistically significant decrease in BMD at the forearm, hip and lumbar spine. A high percentage (6.8%) of healthy Batswana young adults had abnormal baseline BMD Further evaluation is needed of the longer-term use of TDF in HIV-uninfected persons.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="http://clinicaltrials.gov/ct2/show/NCT00448669?term=NCT00448669&rank=1" target="_blank">NCT00448669</a></p></div

Baseline characteristics of TDF2 DXA sub study participants who had at least one DXA bone mineral density scan at forearm, spine and hip: Botswana, 2007–2010.

a<p>These are the 74 participants that only had a baseline DXA scan.</p>b<p>These are the 147 participants that had at least one follow-up DXA scan (Longitudinal cohort).</p

Mean percent bone mineral density (BMD) change (with 95% confidence intervals) from baseline to subsequent months by treatment group (TDF-FTC versus placebo).

<p>Mean percent bone mineral density (BMD) change (with 95% confidence intervals) from baseline to subsequent months by treatment group (TDF-FTC versus placebo).</p