Greater tenofovir-associated renal function decline with protease inhibitor-based versus nonnucleoside reverse-transcriptase inhibitor-based therapy

Background. Plasma concentrations of tenofovir increase when the drug is coadministered with some ritonavir-boosted protease inhibitors (PI/r). We hypothesized that tenofovir disoproxil fumarate (TDF)-treated patients taking PI/r-based regimens would have a greater decline in renal function than patients receiving nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based therapy. Methods. We compared the estimated decline in renal function among 146 human immunodeficiency virus type 1 (HIV-1)-infected patients receiving a TDF + PI/r- (n = 51), TDF + NNRTI- (n = 29), or non-TDF-containing (n = 66) regimen. Plasma tenofovir concentrations were measured at study week 2, and rates of creatinine clearance (CrCl) were estimated using the Cockcroft-Gault (C-G) and Modification of Diet in Renal Disease (MDRD) equations. Mixed-effects models were used to analyze regimen type and tenofovir concentration as predictors of change in CrCl from baseline to weeks 24 and 48. Results. Decreases in C-G estimates of CrCl were not significantly different among the 3 groups during the first 24 weeks of therapy. However, in adjusted analyses, patients receiving TDF + PI/r had a greater rate of decline in CrCl than did the TDF + NNRTI group (for C-G, -13.9 vs. -6.2 mL/min/year [ P = .03]; for MDRD, -14.7 vs. -4.5 mL/min/1.73 m(2)/year [ P = .02]). Among TDF-treated patients, tenofovir plasma concentration was not associated with CrCl over time. Conclusions. Treatment with TDF and PI/r was associated with greater declines in renal function over 48 weeks compared with TDF + NNRTI- based regimens.