Cystatin C-Based Renal Function Changes After Antiretroviral Initiation: A Substudy of a Randomized Trial

BACKGROUND The effects of antiretrovirals on cystatin C-based renal function estimates are unknown. METHODS We analyzed changes in renal function using creatinine and cystatin C-based estimating equations in 269 patients in A5224s, a substudy of study A5202, in which treatment-naive patients were randomized to abacavir/lamivudine or tenofovir/emtricitabine with open-label atazanavir/ritonavir or efavirenz. RESULTS Changes in renal function significantly improved (or declined less) with abacavir/lamivudine treatment compared with tenofovir/emtricitabine using the Cockcroft-Gault formula (P = .016) and 2009 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI; P = .030) and 2012 CKD-EPI cystatin C-creatinine (P = .025). Renal function changes significantly improved (or declined less) with efavirenz compared with atazanavir/ritonavir (P < .001 for all equations). Mean (95% confidence interval) renal function changes specifically for tenofovir/emtricitabine combined with atazanavir/ritonavir were -8.3 (-14.0, -2.6) mL/min with Cockcroft-Gault; -14.9 (-19.7, -10.1) mL/min per 1.73(2) with Modification of Diet in Renal Disease; -12.8 (-16.5, -9.0) mL/min per 1.73(2) with 2009 CKD-EPI; +8.9 (4.2, 13.7) mL/min per 1.73(2) with 2012 CKD-EPI cystatin C; and -1.2 (-5.1, 2.6) mL/min per 1.73(2) with 2012 CKD-EPI cystatin C-creatinine. Renal function changes for the other treatment arms were more favorable but similarly varied by estimating equation. CONCLUSIONS Antiretroviral-associated changes in renal function vary in magnitude and direction based on the estimating equation used.