Objective: Tenofovir disoproxil fumarate (TDF) pre-exposure prophylaxis decreases sexual acquisition of HIV infection. We sought to evaluate the renal safety of TDF in HIV-uninfected persons.
Design and methods: The Iniciativa Profilaxis Pre-Exposición (iPrEx) study randomly assigned 2499 HIV-seronegative men and transgender women who have sex with men (MSM) to receive oral daily TDF coformulated with emtricitabine (FTC/TDF) or placebo. Serum creatinine and phosphorus during randomized treatment and after discontinuation were measured, and creatinine clearance (CrCl) was estimated by the Cockcroft–Gault equation. Indicators of proximal renal tubulopathy (fractional excretion of phosphorus and uric acid, urine protein, and glucose) were measured in a substudy.
Results: There was a small but statistically significant decrease in CrCl from baseline in the active arm, compared to placebo, which was first observed at week 4 (mean change: −2.4 vs. −1.1 ml/min; P = 0.02), persisted through the last on-treatment visit (mean change: +0.3 vs. +1.8 ml/min; P = 0.02), and resolved after stopping pre-exposure prophylaxis (mean change: −0.1 vs. 0.0 ml/min; P = 0.83). The effect was confirmed when stratifying by drug detection. The effect of FTC/TDF on CrCl did not vary by race, age, or history of hypertension. There was no difference in serum phosphate trends between the treatment arms. In the substudy, two participants receiving placebo had indicators of tubulopathy.
Conclusions: In HIV-seronegative MSM, randomization to FTC/TDF was associated with a very mild nonprogressive decrease in CrCl that was reversible and managed with routine serum creatinine monitoring.
aThe Gladstone Institutes
bUniversity of California
cBridge HIV, San Francisco Department of Public Health, San Francisco, USA
dInvestigaciones Medicas en Salud
eAsociación Civil Impacta Salud y Educación, Lima, Peru
fInstituto de Pesquisa Clinica Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
gFenway Institute, Fenway Health, Boston, USA
hResearch Institute for Health Sciences
iDepartment of Community Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
jProjeto Praça Onze, Hospital Escola São Francisco de Assis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
kDesmond Tutu HIV Centre and Department of Medicine, University of Cape Town, Cape Town, South Africa
lDivision of Clinical Immunology and Allergy, School of Medicine, University of São Paulo
mInstituto de Investigação em Imunologia, CEP 05403–900 Cerqueira Cesar, São Paulo, Brazil
nNational Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.
Correspondence to Robert M. Grant, MD, 1650 Owens Street, San Francisco, CA 94158, USA. Tel: +1 415 350 8909; e-mail: firstname.lastname@example.org
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Received June 25, 2013
Accepted November 14, 2013