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

Abstract

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 m2 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 m2 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 m2 per year (p < 0.001). The slope of eGFR reduction was not significantly different in participants with baseline eGFR ≤ 90 mL/min/1.73 m2 (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 m2 between >15 pills/month vs. ≤15 pills/month, p < 0.01) or plasma tenofovir concentrations at the visit (eGFR difference compared to ≤2 ng/mL: >2 to ≤10ng/mL: −0.98 mL/min/1.73 m2, >10 to ≤40ng/mL: −1.28 mL/min/1.73 m2, >40 ng/mL: −1.82 mL/min/1.73 m2, p < 0.001). Three participants discontinued TDF/FTC for eGFR < 60 mL/min/1.73 m2 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.

Kidney function and daily emtricitabine/tenofovir disoproxil fumarate pre-exposure prophylaxis against HIV: results from the real-life multicentric demonstrative project PrEP Brazil

“…This suggests a functional stabilization. The average loss of eGFR over the 48-week follow-up is similar to those found in the Intervention Préventive de l’Exposition aux Risques avec et pour les Gays (ANRS IPERGAY) [ 22 ] and Iniciativa Profilaxis Pre-Exposición Open Label Extension (iPrEx OLE) studies [ 21 ]. Moreover, epidemiological data suggest that significant renal impairment is uncommon in patients with long-term exposure to TDF/FTC [ 20 ].…”

“…Older individuals had a higher frequency of baseline eGFR over 90 mL/min/1.73 m 2 and had significantly greater eGFR losses after the intervention, in agreement with previous reports [ 8 , 20 , 21 ]. We did not observe an association between the degree of eGFR reduction and other traditional risk factors for renal dysfunction, such as arterial hypertension or obesity [ 22 , 23 ]. In contrast to what has been observed in previous studies [ 22 , 23 ], a higher frequency of eGFR reduction was observed amongst individuals who had higher baseline GFR values.…”

“…We did not observe an association between the degree of eGFR reduction and other traditional risk factors for renal dysfunction, such as arterial hypertension or obesity [ 22 , 23 ]. In contrast to what has been observed in previous studies [ 22 , 23 ], a higher frequency of eGFR reduction was observed amongst individuals who had higher baseline GFR values. The main CKD risk factors in the general population are diabetes, hypertension, older age, African-American origin, obesity, and prevalence of cardiovascular disease [ 24 – 26 ].…”

“…Even with the emergence of other drug options such as tenofovir alfenamide, TDF/FTC may still remain a more feasible PrEP option, particularly in low-income countries. This schedule may also be applied to intermittent “On demand” PrEP programs, which have shown effectiveness in HIV protection with a reduced risk to kidney function [ 22 ], but still demand GFR regular monitoring.…”

Kidney function in tenofovir disoproxil fumarate-based oral pre-exposure prophylaxis users: a systematic review and meta-analysis of published literature and a multi-country meta-analysis of individual participant data

“…17 articles reported on 11 different RCTs were included in the metaanalyses. 3,5,[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] . Most studies defined kidney-related adverse events as elevations in serum creatinine levels Forest plots showing risks among tenofovir disoproxil fumarate-based oral PrEP users for grade 1 and higher kidney-adverse events (A) and grade 2 and higher kidney-related adverse events (B).…”