1. Effects of Emtricitabine/Tenofovir on Bone Mineral Density in HIV-Negative Persons in a Randomized, Double-Blind, Placebo-Controlled Trial
- Author
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Mulligan, Kathleen, Glidden, David V, Anderson, Peter L, Liu, Albert, McMahan, Vanessa, Gonzales, Pedro, Ramirez-Cardich, Maria Esther, Namwongprom, Sirianong, Chodacki, Piotr, de Mendonca, Laura Maria Carvalo, Wang, Furong, Lama, Javier R, Chariyalertsak, Suwat, Guanira, Juan Vicente, Buchbinder, Susan, Bekker, Linda-Gail, Schechter, Mauro, Veloso, Valdilea G, Grant, Robert M, Team, for the Preexposure Prophylaxis Initiative Study, Vargas, Lorena, Sanchez, Jorge, Mai, Chiang, Saokhieo, Pongpun, Murphy, Kerry, Gilmore, Hailey, Holland, Sally, Faber, Elizabeth, Duda, John, Bewerunge, Linda, Batist, Elizabeth, Hoskin, Christine, Brown, Ben, de Janeiro, Rio, Beppu-Yoshida, Carina, da Costa, Marcellus Dias, de Jesus, Sergio Carlos Assis, da Silva, Jose Roberto Grangeiro, Millan, Roberta, de Siqueira Hoagland, Brenda Regina, Fernandes, Nilo Martinez, da Silva Freitas, Lucilene, Grinsztejn, Beatriz, Pilotto, Jose, Bushman, Lane, Zheng, Jia-Hua, Guida, Louis Anthony, Kline, Brandon, Goicochea, Pedro, Manzo, Jonathan, Hance, Robert, McConnell, Jeff, Defechereux, Patricia, Levy, Vivian, Robles, Malu, Postle, Brian, Burns, David, and Rooney, James
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Trials and Supportive Activities ,Osteoporosis ,Prevention ,HIV/AIDS ,Clinical Research ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Absorptiometry ,Photon ,Administration ,Oral ,Adolescent ,Adult ,Anti-HIV Agents ,Bone Density ,Chemoprevention ,Cytoplasm ,Double-Blind Method ,Emtricitabine ,Female ,HIV Infections ,Humans ,Male ,Middle Aged ,Placebos ,Plasma ,Tenofovir ,Young Adult ,bone ,tenofovir ,emtricitabine ,PrEP ,DXA ,Preexposure Prophylaxis Initiative Study Team ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Clinical sciences - Abstract
BackgroundDaily 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.MethodsDual-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.ResultsIn 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.ConclusionsIn 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.Clinical trials registrationNCT00458393.
- Published
- 2015