Changes in kidney function among men having sex with men starting on demand tenofovir disoproxil fumarate--emtricitabine for HIV pre-exposure prophylaxis

Introduction: Daily pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) is associated with a small but statistically significant decrease in estimated glomerular filtration rate (eGFR). We assessed the renal safety of on-demand PrEP with TDF/FTC in HIV-1 uninfected men. Methods: We used data from the randomized double-blind placebo-controlled ANRS-IPERGAY trial and its open-label extension conducted between February 2012 and June 2016 among HIV-uninfected MSM starting on-demand PrEP. Using linear mixed model, we evaluated the mean eGFR decline from baseline over time and determined risks factors associated with eGFR decline during the study. Results: During the blind phase, with a median follow-up of 9.4 months, the mean decline slope of eGFR from baseline was -0.88 and -1.53 mL/min/1.73 [m.sup.2] per year in the placebo (n = 201) and the TDF/FTC group (n = 198) respectively, with a slope difference of 0.65 mL/min/1.73 [m.sup.2] per year (p = 0.27). Including both phases, 389 participants started on-demand TDF/FTC with a median follow-up of 19.2 months and a mean decline of eGFR from baseline of -1.14 mL/min/1.73 [m.sup.2] per year (p < 0.001). The slope of eGFR reduction was not significantly different in participants with baseline eGFR [less than or equal to] 90 mL/min/1.73 [m.sup.2] (p = 0.44), age >40 years (p = 0.24) or hypertension (p = 0.21). There was a dose-response relationship between recent tenofovir exposure and lower eGFR when considering the number of pills taken in the two months prior the visit (eGFR difference of -0.88 mL/min/1.73 [m.sup.2] between >15 pills/month vs. [less than or equal to]15 pills/month, p < 0.01) or plasma tenofovir concentrations at the visit (eGFR difference compared to [less than or equal to]2 ng/mL: >2 to [less than or equal to]10ng/mL: -0.98 mL/min/1.73 [m.sup.2], >10 to [less than or equal to]40ng/mL: -1.28 mL/min/1.73 [m.sup.2], >40 ng/mL: -1.82 mL/min/1.73 [m.sup.2], p < 0.001). Three participants discontinued TDF/FTC for eGFR < 60 mL/min/1.73 [m.sup.2] during the OLE phase. No case of Fanconi syndrome was reported. Conclusions: The renal safety of on-demand PrEP with TDF/FTC was good. The overall reduction and intermittent exposure to TDF/FTC may explain this good renal safety. Keywords: PrEP; on-demand; intermittent; kidney; eGFR; tenofovir; HIV
1 | INTRODUCTION Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF)--emtricitabine (FTC) raises a lot of expectations to hamper HIV epidemic due to its high effectiveness to prevent HIV acquisition [...]