Effects of Emtricitabine/Tenofovir on Bone Mineral Density in HIV-Negative Persons in a Randomized, Double-Blind, Placebo-Controlled Trial

Kathleen Mulligan, David V. Glidden, Peter L. Anderson, Albert Liu, Vanessa McMahan, Pedro Gonzales, Maria Esther Ramirez-Cardich, Sirianong Namwongprom, Piotr Chodacki, Laura Maria Carvalo De Mendonca, Furong Wang, Javier R. Lama, Suwat Chariyalertsak, Juan Vicente Guanira, Susan Buchbinder, Linda Gail Bekker, Mauro Schechter, Valdilea G. Veloso, Robert M. Grant, Lorena VargasJorge Sanchez, Chiang Mai, Pongpun Saokhieo, Kerry Murphy, Hailey Gilmore, Sally Holland, Elizabeth Faber, John Duda, Linda Bewerunge, Elizabeth Batist, Christine Hoskin, Ben Brown, Rio De Janeiro, Carina Beppu-Yoshida, Marcellus Dias Da Costa, Sergio Carlos Assis De Jesus, Jose Roberto Grangeiro Da Silva, Roberta Millan, Brenda Regina De Siqueira Hoagland, Nilo Martinez Fernandes, Lucilene Da Silva Freitas, Beatriz Grinsztejn, Jose Pilotto, Lane Bushman, Jia Hua Zheng, Louis Anthony Guida, Brandon Kline, Pedro Goicochea, Jonathan Manzo, Robert Hance, Jeff McConnell, Patricia Defechereux, Vivian Levy, Malu Robles, Brian Postle, David Burns, James Rooney

Research output: Contribution to journalArticlepeer-review

114 Scopus citations

Abstract

Background. Daily preexposure prophylaxis (PrEP) with oral emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) decreases the risk of human immunodeficiency virus (HIV) acquisition. Initiation of TDF decreases bone mineral density (BMD) in HIV-infected people. We report the effect of FTC/TDF on BMD in HIV-seronegative men who have sex with men and in transgender women. Methods. Dual-energy X-ray absorptiometry was performed at baseline and 24-week intervals in a substudy of iPrEx, a randomized, double-blind, placebo-controlled trial of FTC/TDF PrEP. Plasma and intracellular tenofovir concentrations were measured in participants randomized to FTC/TDF. Results. In 498 participants (247 FTC/TDF, 251 placebo), BMD in those randomized to FTC/TDF decreased modestly but statistically significantly by 24 weeks in the spine (net difference, -0.91% [95% confidence interval {CI}, -1.44% to -.38%]; P =. 001) and hip (-0.61% [95% CI, -.96% to -.27%], P =. 001). Changes within each subsequent 24-week interval were not statistically significant. Changes in BMD by week 24 correlated inversely with intracellular tenofovir diphosphate (TFV-DP), which was detected in 53% of those randomized to FTC/TDF. Net BMD loss by week 24 in participants with TFV-DP levels indicative of consistent dosing averaged -1.42% ± 29% and -0.85% ± 19% in the spine and hip, respectively (P <. 001 vs placebo). Spine BMD tended to rebound following discontinuation of FTC/TDF. There were no differences in fractures (P =. 62) or incidence of low BMD. Conclusions. In HIV-uninfected persons, FTC/TDF PrEP was associated with small but statistically significant decreases in BMD by week 24 that inversely correlated with TFV-DP, with more stable BMD thereafter.

Original languageEnglish (US)
Pages (from-to)572-580
Number of pages9
JournalClinical Infectious Diseases
Volume61
Issue number4
DOIs
StatePublished - Aug 15 2015
Externally publishedYes

Keywords

  • DXA
  • PrEP
  • bone
  • emtricitabine
  • tenofovir

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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