Several trials have demonstrated the safety and efficacy of TDF/FTC pre-exposure prophylaxis (PrEP). Renal toxicity was uncommon in randomized trials of healthy individuals, but has not been assessed in clinical settings. We evaluated changes in renal function among participants enrolled in the open-label US PrEP Demonstration Project.
The Demo Project enrolled HIV-negative MSM and transwomen (TGW) in STI clinics and a community health center. Eligible participants [creatinine clearance (CrCl) ≥60 ml/min] were offered 48 weeks of TDF/FTC PrEP. Creatinine (Cr) was measured every 12 weeks and CrCl estimated by the Cockcroft Gault equation. Tenofovir diphosphate (TFV-DP) levels in dried blood spots (DBS) were measured in a subset of subjects. The associations of time-dependent factors with visit-to-visit changes in CrCl were assessed using linear mixed models.
From October 2012 to January 2014, 557 MSM and TGW enrolled. Median age was 35 (range 18-65); 48% were White, 35% Latino, 7% Black, 5% Asian, and 6% other; 98% were MSM. Baseline median Cr was 0.92 (0.59-1.55), with a median CrCl of 124 ml/min (71-309). DBS were tested at 1,067 person-visits among 294 participants, with TFV-DP levels consistent with ≥4 doses/week in 82% of person-visits. Median CrCl declined 6 ml/min (5%) from baseline to week 12 and remained stable through week 48 (p=0.96), with no differences by race/ethnicity, weight, or NSAID use. However, 30% had >10% decline in CrCl at week 12. TFV-DP levels ≥2 vs. <2 doses/week were associated with a greater decline in CrCl at week 12 (-7.6 ml/min vs. +3.6 ml/min, p=0.001) (figure). In a multivariable model, age<25 (7.7 ml/min greater decline), use of hypertension or diabetes medications (6.1 ml/min greater decline), and TFV-DP levels ≥2 doses/week (12.8 ml/min greater decline) were independently associated with greater CrCl loss. The age effect was not explained by alcohol or recreational drug use. No subjects had CrCl <60 ml/min during follow-up. TDF/FTC was held in 3 subjects due to elevated creatinine, however these were not confirmed on repeat testing, and PrEP was restarted in all cases with no further interruptions.
MSM initiating PrEP in the Demo Project had an overall modest, non-progressive decline in renal function, with a threshold effect for TFV-DP levels >2 doses/week. Younger PrEP users and those taking medications for hypertension or diabetes had greater decreases in CrCl and may warrant additional monitoring during PrEP use.