Increased Time Exposure To Tenofovir Is Associated With A Greater Decrease In Estimated Glomerular Filtration Rate In Hiv Patients With Kidney Function Of Less Than 60 Ml/Min/1.73 M(2)

Tenofovir (TDF), atazanovir (ATAZ) and indinavir (IND) have been reported as possible risk factors for incident chronic kidney disease (CKD) in HIV-infected patients. We investigated the relationship between the duration of antiretroviral exposure and estimated glomerular filtration rate (eGFR) evolution in CKD patients. In a cohort of 1,750 HIV-infected patients, we identified 121 CKD patients with a mean follow-up of 44 8 35 months. The relationship between mean eGFR at baseline, eGFR slope and time exposure to antiretroviral treatment as well as confounding factors were investigated using a joint modeling procedure. Seventy (58%), 30 (25%) and 33 patients (27%), with a mean age of 50.3 +/- 11.7 years, mean eGFR at baseline of 53.0 +/- 0.8 (ml/min/1.73 m(2)) and eGFR slope of 0.46 +/- 0.07 ml/min/1.73 m(2)/year, were exposed to TDF, ATAZ and IND, respectively. In univariate analysis, hepatitis C virus infection, decreased nadir of log CD4 count, high blood pressure at baseline, angiotensin-converting enzyme inhibitor treatment and greater time exposure to TDF during follow-up were associated with a higher slope, whereas greater time exposure to IND was associated with a lower slope. In multivariate analysis, higher TDF time exposure was still significantly associated with eGFR decline, with a dose-effect relationship (slope +/- standard error of the mean: 1.1 +/- 0.1, 0.5 +/- 0.1, -0.07 +/- 0.08 and -0.87 +/- 0.06 ml/min/1.73 m(2)/year for no time exposure, <34, 34-67 and >= 67%, respectively; trend test: p < 0.001), whereas the IND time exposure association was abolished. In HIV patients with CKD, a greater TDF time exposure was independently associated, in a graded manner, with a greater eGFR decline. Copyright (c) 2012 S. Karger AG, Basel