TY - JOUR
T1 - Effects of Emtricitabine/Tenofovir on Bone Mineral Density in HIV-Negative Persons in a Randomized, Double-Blind, Placebo-Controlled Trial
AU - Mulligan, Kathleen
AU - Glidden, David V.
AU - Anderson, Peter L.
AU - Liu, Albert
AU - McMahan, Vanessa
AU - Gonzales, Pedro
AU - Ramirez-Cardich, Maria Esther
AU - Namwongprom, Sirianong
AU - Chodacki, Piotr
AU - De Mendonca, Laura Maria Carvalo
AU - Wang, Furong
AU - Lama, Javier R.
AU - Chariyalertsak, Suwat
AU - Guanira, Juan Vicente
AU - Buchbinder, Susan
AU - Bekker, Linda Gail
AU - Schechter, Mauro
AU - Veloso, Valdilea G.
AU - Grant, Robert M.
AU - Vargas, Lorena
AU - Sanchez, Jorge
AU - Mai, Chiang
AU - Saokhieo, Pongpun
AU - Murphy, Kerry
AU - Gilmore, Hailey
AU - Holland, Sally
AU - Faber, Elizabeth
AU - Duda, John
AU - Bewerunge, Linda
AU - Batist, Elizabeth
AU - Hoskin, Christine
AU - Brown, Ben
AU - De Janeiro, Rio
AU - Beppu-Yoshida, Carina
AU - Da Costa, Marcellus Dias
AU - Assis De Jesus, Sergio Carlos
AU - Grangeiro Da Silva, Jose Roberto
AU - Millan, Roberta
AU - De Siqueira Hoagland, Brenda Regina
AU - Martinez Fernandes, Nilo
AU - Da Silva Freitas, Lucilene
AU - Grinsztejn, Beatriz
AU - Pilotto, Jose
AU - Bushman, Lane
AU - Zheng, Jia Hua
AU - Anthony Guida, Louis
AU - Kline, Brandon
AU - Goicochea, Pedro
AU - Manzo, Jonathan
AU - Hance, Robert
AU - McConnell, Jeff
AU - Defechereux, Patricia
AU - Levy, Vivian
AU - Robles, Malu
AU - Postle, Brian
AU - Burns, David
AU - Rooney, James
N1 - Publisher Copyright:
© 2015 The Author 2015.
PY - 2015/8/15
Y1 - 2015/8/15
N2 - 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.
AB - 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.
KW - DXA
KW - PrEP
KW - bone
KW - emtricitabine
KW - tenofovir
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U2 - 10.1093/cid/civ324
DO - 10.1093/cid/civ324
M3 - Article
C2 - 25908682
AN - SCOPUS:84938598621
SN - 1058-4838
VL - 61
SP - 572
EP - 580
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 4
ER -