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

ABSTRACT: 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 HIV-infected 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: ?1-microglobulin (?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 open-label 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 ?1m, albuminuria, or proteinuria by treatment arm. In iPrEx-OLE, after 24 weeks on PrEP, urine ?1m and proteinuria increased by 21% [95% confidence interval (CI): 10 to 33] and 18% (95% CI: 8 to 28), respectively. The prevalence of detectable ?1m increased from 44% to 65% (P < 0.001) and estimated glomerular filtration rate declined by 4 mL/min/1.73 m (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 ?1m and proteinuria after 6 months, suggesting that PrEP may result in subclinical tubule dysfunction.

SUBMITTER: Jotwani V 

PROVIDER: S-EPMC6071417 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature