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Suppression of HIV-1 replication by antiretroviral therapy improves renal function in persons with low CD4 cell counts and chronic kidney disease

Kalayjian, Robert Ca; Franceschini, Norac; Gupta, Samir Ke; Szczech, Lynda Ad; Mupere, Ezekielg; Bosch, Ronald Jf; Smurzynski, Marlenef; Albert, Jeffrey Mb

doi: 10.1097/QAD.0b013e3282f4706d
Clinical Science

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 ≥ 2 and low baseline CD4 cell counts (< 200 cells/μl). 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 m2 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.

From the aDepartment of Medicine, MetroHealth Medical Center

bDepartment of Epidemiology, Case School of Medicine, Cleveland, Ohio

cDepartment of Epidemiology, University of North Carolina School of Public Health, Chapel Hill

dDepartment of Medicine, Duke University Medical Center, Durham, North Carolina

eDepartment of Medicine, Indiana University School of Medicine, Indianapolis, Indiana

fCenter for Biostatistics in AIDS Research, Hartard School of Public Health, Boston Massachusetts, USA

gDepartment of Paediatrics and Child Health Faculty of Medicine, Makerere University, Kampala, Uganda.

Received 5 July, 2007

Revised 1 November, 2007

Accepted 13 November, 2007

Correspondence to Dr R.C. Kalayjian, Division of Infectious Diseases, MetroHealth Medical Center, 2500 MetroHealth Dr, Cleveland, Ohio, USA. E-mail: rkalayjian@metrohealth.org

© 2008 Lippincott Williams & Wilkins, Inc.