P20.03
Background: Oral tenofovir disoproxil fumarate (TDF)-based pre-exposure prophylaxis (PrEP) protects against HIV acquisition. TDF use has been associated with declines in estimated glomerular filtration rate (eGFR) when used as part of antiretroviral treatment by HIV infected persons but limited data are available for risk when used as PrEP by HIV uninfected adults, especially among those with high PrEP adherence.
Methods: We conducted a safety analysis of the change in eGFR in the Partners PrEP Study, a randomized, placebo-controlled trial of daily oral TDF and emtricitabine (FTC)-TDF PrEP among heterosexual HIV uninfected members of serodiscordant couples. PrEP adherence was high in the study population. eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration Equation.
Results: A total of 4631 subjects were randomized to once daily TDF (n=1545), FTC-TDF (n=1542), or placebo (n=1544) and followed for a median of 18 months (IQR 12-27). 62% of subjects were male and the median age at enrollment was 35 years (range 18-64). Overall, mean eGFR change from baseline that was attributable to PrEP compared to placebo was −1.23 mL/min/1.73m2 (95% CI −2.06, −0.40; p=0.004) for TDF and −1.58 mL/min/1.73m2 (95% CI −2.42, −0.73; p<0.001) for FTC-TDF. The difference in eGFR between PrEP and placebo appeared by 4 weeks after randomization, was stable through 12 months, and then gradually waned. There was no statistically significant increase in the incidence of a≥25% decline in eGFR attributable to PrEP compared to placebo: incidence rate per 100 person-years 1.00 for TDF, 1.14 for FTC-TDF, and 0.76 for placebo (adjusted Hazard Ratios 1.34, 95% CI 0.72, 2.50; p=0.36 for TDF and 1.45, 95% CI 0.80, 2.64; p=0.23 for FTC-TDF).
Conclusions: In this large randomized, placebo-controlled trial, TDF-based PrEP was associated with a small although statistically significant decline in eGFR. However, there was no significant increase in the risk of clinically relevant (≥25%) eGFR decline related to PrEP.
