OBJECTIVE: To examine the association between changes in glomerular filtration rates (GFR) and antiretroviral therapy (ART)-mediated suppression of plasma HIV-1 viremia. DESIGN:: Observational, prospective, multicenter cohort study. INTERVENTION: ART regimens or treatment strategies in HIV-1-infected subjects were implemented through randomized clinical trials; 1776 ambulatory subjects from these trials also enrolled in this cohort study. METHOD: The association between suppression of viremia and GFR changes from baseline was examined using the abbreviated Modification of Diet and Renal Disease equation in mixed effects linear models. RESULTS: GFR improvement was associated with ART-mediated suppression of plasma viremia in subjects with both chronic kidney disease stage > or = 2 and low baseline CD4 cell counts (< 200 cells/microl). In this subset, viral suppression (by > 1.0 log10 copies/ml or to < 400 copies/ml) was associated with an average increase in GFR of 9.2 ml/min per 1.73 m(2) from baseline (95% confidence interval, 1.6-16.8; P = 0.02) over a median follow-up of 160 weeks. The magnitude of this association increased in subjects who had greater baseline impairment of renal function, and it did not depend on race or sex. CONCLUSIONS: Viral suppression was associated with GFR improvements in those with both low CD4 cell counts and impaired baseline renal function, supporting an independent contribution of HIV-1 replication to chronic renal dysfunction in advanced HIV disease. GFR improvement not associated with viral suppression also was observed in subjects with higher CD4 cell counts.