Association between tenofovir exposure and reduced kidney function in a cohort of HIV-positive patients: Results from 10 years of follow-up

Abstract

Background. Some studies have shown that tenofovir disoproxil fumarate (TDF), a drug widely used in highly active antiretroviral therapy, is associated with kidney dysfunction, but the magnitude of the effect and its clinical impact is still being debated. Our objective was to evaluate the association between long-term TDF exposure and kidney dysfunction in a cohort of 1043 human immunodeficiency virus-positive patients followed up for 10 years and to quantify the loss in estimated glomerular filtration rate (eGFR) in patients exposed to TDF in comparison with those exposed to other antiretroviral therapies.Methods. Adjusted hazard ratios (HR) and odds ratios (OR) for the association between TDF and kidney dysfunction (defined as eGFR <90 mL/min/1.73 m2) were calculated using the Cox proportional hazards model and generalized estimating equations. Mean loss in eGFR attributable to TDF by cumulative years of exposure was estimated using linear regressions.Results. Tenofovir exposure increased the risk of kidney dysfunction by 63% (HR, 1.63; 95% confidence interval, 1.26-2.10). The cumulative eGFR loss directly attributable to TDF after 1, 2, 3, and 4 years of TDF exposure was-3.05 (P =. 017),-4.05 (P =. 000),-2.42 (P =. 023), and-3.09 mL/min/1.73 m2 (P =. 119), respectively, which shows that most of the loss occurred during the first years of exposure. Conclusions. In this cohort, TDF exposure was associated with reduced kidney function, but the loss in eGFR attributable to TDF is relatively mild in a long-term perspective. © 2012 The Author 2012. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.