Pre-exposure Prophylaxis With Tenofovir Disoproxil Fumarate/Emtricitabine and Kidney Tubular Dysfunction in HIV-Uninfected Individuals

Background: Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) is becoming increasingly adopted for HIV prevention. Tenofovir can cause proximal tubular damage and chronic kidney disease in HIVinfected persons, but little is known regarding its nephrotoxic potential among HIV-uninfected persons. In this study, we evaluated the effects of PrEP on urine levels of the following: alpha 1-microglobulin (alpha 1m), a marker of impaired tubular reabsorption; albuminuria, a measure of glomerular injury; and total proteinuria. Setting: The Iniciativa Profilaxis Pre-Exposicion (iPrEx) study randomized HIV-seronegative men and transgender women who have sex with men to oral TDF/FTC or placebo. The iPrEx openlabel extension (iPrEx-OLE) study enrolled former PrEP trial participants to receive open-label TDF/FTC. Methods: A cross-sectional analysis compared urine biomarker levels by study arm in iPrEx (N = 100 treatment arm, N = 100 placebo arm). Then, urine biomarker levels were compared before and after PrEP initiation in 109 participants of iPrEx-OLE. Results: In iPrEx, there were no significant differences in urine alpha 1m, albuminuria, or proteinuria by treatment arm. In iPrEx-OLE, after 24 weeks on PrEP, urine alm and proteinuria increased by 21% [95% confidence interval (CD: 10 to 33] and 18% (95% CI: 8 to 28), respectively. The prevalence of detectable alpha 1m increased from 44% to 65% (P < 0.001) and estimated glomerular filtration rate declined by 4 mL/min/1.73 m(2) (P < 0.001). There was no significant change in albuminuria (6%; 95% CI: -7% to 20%). Conclusion: PrEP with TDF/FTC was associated with a statistically significant rise in urine alpha 1m and proteinuria after 6 months, suggesting that PrEP may result in subclinical tubule dysfunction.