| dc.description.abstract | IMPORTANCE Tenofovir disoproxil fumarate (TDF) use has been associated with declines in
the estimated glomerular filtration rate (eGFR) when used as part of antiretroviral treatment
by persons with human immunodeficiency virus (HIV) type 1, but limited data are available for
risk when used as preexposure prophylaxis (PrEP) for HIV-1 prevention.
OBJECTIVE To determine whether TDF-based PrEP causes eGFR decline in HIV-1–uninfected
adults.
DESIGN, SETTING, AND PARTICIPANTS A per-protocol safety analysis of changes in eGFR in the
Partners PrEP Study, a randomized, placebo-controlled trial of daily oral TDF and
emtricitabine (FTC)-TDF PrEP among heterosexual HIV-1–uninfected members of
serodiscordant couples in Kenya and Uganda. The trial was conducted from 2008 to 2012.
MAIN OUTCOMES AND MEASURES Predefined outcomes of this analysiswere mean eGFR
change and a 25%or greater eGFR decline from baseline. The eGFR was calculated using the
Chronic Kidney Disease Epidemiology Collaboration equation.
RESULTS Of 4640 participants in the once-daily TDF (n = 1548), FTC-TDF (n = 1545), or
placebo (n = 1547) groups, 63%were men. At enrollment, median age was 35 years (range,
18-64 years), and mean eGFR was 130 mL/min/1.73m2. During a median follow-up of 18
months (interquartile range 12-27 months), mean within-group eGFR change from baseline
was +0.14 mL/min/1.73m2 for TDF, −0.22 mL/min/1.73m2 for FTC-TDF, and +1.37 mL/min/1.73
m2 for placebo, translating into average declines in eGFR attributable to PrEP vs placebo of
−1.23 mL/min/1.73m2 (95%CI, −2.06 to −0.40; P = .004) for TDF and −1.59 mL/min/1.73m2
(95%CI, −2.44 to −0.74; P < .001) for FTC-TDF. The difference in mean eGFR between PrEP
and placebo appeared by 1 month after randomization, was stable through 12 months, and
then appeared to wane thereafter. The respective proportions of persons who developed a
confirmed 25%or greater eGFR decline from baseline by 12 and 24 months was 1.3%and
1.8%for TDF and 1.2%and 2.5%for FTC-TDF, and these frequencies were not statistically
different from the confirmed decline in the placebo group (0.9%and 1.3%by 12 and 24
months, respectively).
CONCLUSIONS AND RELEVANCE In this large randomized, placebo-controlled trial among
heterosexual persons, with median follow-up of 18 months and maximum follow-up of 36
months, daily oral TDF-based PrEP resulted in a small but nonprogressive decline in eGFR
that was not accompanied by a substantial increase in the risk of clinically relevant ( 25%)
eGFR decline. | en_US |
