Bone mineral density changes among HIV-uninfected young adults in a randomised trial of pre-exposure prophylaxis with tenofovir-emtricitabine or placebo in Botswana

PLoS One. 2014 Mar 13;9(3):e90111. doi: 10.1371/journal.pone.0090111. eCollection 2014.

Abstract

Background: 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.

Method: 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.

Results: 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)].

Conclusion: 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.

Trial registration: ClinicalTrials.gov NCT00448669.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Absorptiometry, Photon
  • Adolescent
  • Adult
  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / adverse effects
  • Bone Density / drug effects*
  • Botswana
  • Communicable Disease Control
  • Emtricitabine / administration & dosage*
  • Emtricitabine / adverse effects
  • Female
  • Forearm / diagnostic imaging
  • HIV Infections / prevention & control*
  • Hip / diagnostic imaging
  • Humans
  • Longitudinal Studies
  • Male
  • Pre-Exposure Prophylaxis / methods*
  • Spine / diagnostic imaging
  • Tenofovir / administration & dosage*
  • Tenofovir / adverse effects
  • Young Adult

Substances

  • Anti-HIV Agents
  • Tenofovir
  • Emtricitabine

Associated data

  • ClinicalTrials.gov/NCT00448669

Grant support

The study was supported by the Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, and the Division of AIDS, National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.