Brief Report: Tenofovir-Associated Nephrotoxicity Among a US National Historical Cohort of HIV-Infected Veterans: Risk Modification by Concomitant Antiretrovirals.

Abstract

Tenofovir disoproxil fumarate (TDF) has been associated with renal complications. The third agent in TDF-containing antiretroviral regimens may modify that risk. We compared renal adverse outcomes among treatment-naive HIV-infected patients initiating TDF-containing regimens including efavirenz (EFV) or other agents. This population-based historical cohort study used national Veterans Health Administration (VHA) clinical and administrative data sets to identify treatment-naive HIV-infected veterans initiating antiretroviral therapy with TDF/emtricitabine (FTC) + EFV, rilpivirine (RPV), elvitegravir/cobicistat (EVG/c), or ritonavir (RTV)-boosted protease inhibitors (PIs) from 2003 to 2015. Unadjusted incidence rates (IRs) for each regimen and covariate-adjusted hazard ratios [ using Cox proportional hazards models and inverse probability of treatment weighting] for between-regimen comparisons were calculated for renal outcomes including confirmed proteinuria, defined as 2 consecutive protein-to-creatinine ratios >150 mg/g or albumin-to-creatinine ratios >30 mg/g occurring ≥90 days apart; chronic kidney disease (CKD), defined as 2 consecutive estimated glomerular filtration rate measurements <60 mL·min·1.73 m occurring ≥90 days apart; and kidney dialysis. Of 33,048 HIV-positive veterans, 4172 received EFV + TDF/FTC, 234 EVG/c/TDF/FTC, 173 RPV/TDF/FTC, and 2651 RTV-boosted PIs + TDF/FTC. Confirmed proteinuria and CKD IRs were numerically lower with EFV + TDF/FTC versus non-EFV + TDF/FTC (dialysis IRs were rare and comparable). After inverse probability of treatment weighting adjustment, EFV + TDF/FTC was associated with lower CKD risk versus non-EFV + TDF/FTC (hazard ratio, 0.62; 95% confidence interval, 0.53 to 0.72), EVG/c/TDF/FTC (0.75; 0.59 to 0.95), RPV/TDF/FTC (0.20; 0.17 to 0.24), and RTV-boosted PIs + TDF/FTC (0.62; 0.53 to 0.72). EFV + TDF/FTC was associated with significantly lower risk of CKD versus other TDF-containing regimens in the Veterans Health Administration.