Changes in renal function associated with oral emtricitabine/tenofovir disoproxil fumarate use for HIV pre-exposure prophylaxis.
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.


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.
Marc M
MM
Solomon
Javier R
JR
Lama
David V
DV
Glidden
Kathleen
K
Mulligan
Vanessa
V
McMahan
Albert Y
AY
Liu
Juan Vicente
JV
Guanira
Valdilea G
VG
Veloso
Kenneth H
KH
Mayer
Suwat
S
Chariyalertsak
Mauro
M
Schechter
Linda-Gail
LG
Bekker
Esper Georges
EG
Kallás
David N
DN
Burns
Robert M
RM
Grant
D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018890:Chemoprevention / Q000009:adverse effects / Q000379:methods*; D003404:Creatinine / Q000097:blood; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000517:prevention & control*; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D007677:Kidney Function Tests; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D063065:Organophosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D010758:Phosphorus / Q000097:blood; D010919:Placebos / Q000008:administration & dosage; D000068698:Tenofovir; D055815:Young Adult
D019380:Anti-HIV Agents; D063065:Organophosphonates; D010919:Placebos; D003841:Deoxycytidine; D010758:Phosphorus; D000068698:Tenofovir; D003404:Creatinine; D000068679:Emtricitabine; D000225:Adenine