title: Effects of Emtricitabine/Tenofovir on Bone Mineral Density in HIV-Negative Persons in a Randomized, Double-Blind, Placebo-Controlled Trial.
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.
  
  
  BACKGROUND
  NCT00458393.
authors.affiliation: University of California, San Francisco.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Mulligan
authors.affiliation: University of California, San Francisco.
authors.forename: David V
authors.initials: DV
authors.lastname: Glidden
authors.affiliation: University of Colorado Denver, Aurora.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Anderson
authors.affiliation: University of California, San Francisco Bridge HIV, San Francisco Department of Public Health, California.
authors.forename: Albert
authors.initials: A
authors.lastname: Liu
authors.affiliation: Gladstone Institute of Virology and Immunology, San Francisco, California.
authors.forename: Vanessa
authors.initials: V
authors.lastname: McMahan
authors.affiliation: Investigaciones Medicas en Salud.
authors.forename: Pedro
authors.initials: P
authors.lastname: Gonzales
authors.affiliation: Asociacion Civil Impacta Salud y Education, Lima, Peru.
authors.forename: Maria Esther
authors.initials: ME
authors.lastname: Ramirez-Cardich
authors.affiliation: Chiang Mai University, Thailand.
authors.forename: Sirianong
authors.initials: S
authors.lastname: Namwongprom
authors.affiliation: Desmond Tutu HIV Centre and Department of Medicine, University of Cape Town, South Africa.
authors.forename: Piotr
authors.initials: P
authors.lastname: Chodacki
authors.affiliation: Federal University of Rio de Janeiro, Brazil.
authors.forename: Laura Maria Carvalo
authors.initials: LM
authors.lastname: de Mendonca
authors.affiliation: University of California, San Francisco.
authors.forename: Furong
authors.initials: F
authors.lastname: Wang
authors.affiliation: Asociacion Civil Impacta Salud y Education, Lima, Peru.
authors.forename: Javier R
authors.initials: JR
authors.lastname: Lama
authors.affiliation: Chiang Mai University, Thailand Research Institute for Health Sciences, Chiang Mai, Thailand.
authors.forename: Suwat
authors.initials: S
authors.lastname: Chariyalertsak
authors.affiliation: Investigaciones Medicas en Salud.
authors.forename: Juan Vicente
authors.initials: JV
authors.lastname: Guanira
authors.affiliation: University of California, San Francisco Bridge HIV, San Francisco Department of Public Health, California.
authors.forename: Susan
authors.initials: S
authors.lastname: Buchbinder
authors.affiliation: Desmond Tutu HIV Centre and Department of Medicine, University of Cape Town, South Africa.
authors.forename: Linda-Gail
authors.initials: LG
authors.lastname: Bekker
authors.affiliation: Federal University of Rio de Janeiro, Brazil Projeto Praca Onze, Hospital Escola Sao Francisco de Assis.
authors.forename: Mauro
authors.initials: M
authors.lastname: Schechter
authors.affiliation: Instituto de Pesquisa Clinica Evandro Chagas-Fundaçao Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Valdilea G
authors.initials: VG
authors.lastname: Veloso
authors.affiliation: University of California, San Francisco Gladstone Institute of Virology and Immunology, San Francisco, California.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Grant
mesh_terms: D015502:Absorptiometry, Photon; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015519:Bone Density / Q000187:drug effects*; D018890:Chemoprevention / Q000379:methods*; D003593:Cytoplasm / Q000737:chemistry; D004311:Double-Blind Method; D000068679:Emtricitabine / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D015658:HIV Infections / Q000517:prevention & control*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D010949:Plasma / Q000737:chemistry; D000068698:Tenofovir / Q000008:administration & dosage / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D010919:Placebos; D000068698:Tenofovir; D000068679:Emtricitabine
keywords: DXA; PrEP; bone; emtricitabine; tenofovir