Reversibility of kidney function decline in HIV-1–uninfected men and women using preexposure prophylaxis

Abstract

Background: Tenofovir disoproxil fumarate pre-exposure prophylaxis (PrEP) use is associated with a small but statistically significant decline in estimated glomerular filtration rate (eGFR). We investigated the occurrence and reversibility of eGFR decline among HIV-1 uninfected adults discontinuing PrEP. Methods: Data are from the Partners PrEP Study, a trial of daily oral tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC)/TDF PrEP among 4747 African HIV-1 uninfected men and women who had normal baseline renal parameters. Renal function was assessed at baseline, month 1, and then quarterly while on study medication and up to 2 monthly visits in the post-study drug follow-up phase. eGFR was calculated using the Chronic Kidney Disease Epidemiolgy Collaboration Equation. Results: A total of 3944 individuals had a post-study drug visit within 12 weeks of drug discontinuation (1277 in TDF group, 1309 in FTC-TDF group, and 1358 for placebo); 64% were male, median age was 34 (range 18–64) years, and mean eGFR was similar at baseline (p>0.05). Median time on study drug was 33 (IQR 25–36) months. Compared to placebo (Figure 1), mean eGFR for PrEP was slightly but statistically significantly lower at the last on-treatment visit (128 mL/min/173m2 for TDF and FTC-TDF vs 130 mL/min/173m2 for placebo; p≤0.01). This difference reversed to within baseline levels by 4 weeks after PrEP discontinuation (130 mL/min/173m2 for TDF, 129 mL/min/173m2 for FTC-TDF vs 130 mL/ min/173m2 for placebo eGFR; p>0.2 for all). Consistent patterns were observed for serum phosphorus Conclusions: In this large study among African men and women who had a median TDF-exposure of 33 months, the reduction in mean eGFR was small and returned to within baseline levels by 4 weeks after discontinuation of TDF-based PrEP