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Estimated glomerular filtration rate, chronic kidney disease and antiretroviral drug use in HIV-positive patients

Mocroft, Amandaa; Kirk, Oleb; Reiss, Peterc; De Wit, Stephaned; Sedlacek, Dalibore; Beniowski, Marekf; Gatell, Joseg; Phillips, Andrew Na; Ledergerber, Brunoh; Lundgren, Jens Db,i; for the EuroSIDA Study Group

doi: 10.1097/QAD.0b013e328339fe53
Clinical Science

Objectives: Chronic kidney disease (CKD) in HIV-positive persons might be caused by both HIV and traditional or non-HIV-related factors. Our objective was to investigate long-term exposure to specific antiretroviral drugs and CKD.

Design: A cohort study including 6843 HIV-positive persons with at least three serum creatinine measurements and corresponding body weight measurements from 2004 onwards.

Methods: CKD was defined as either confirmed (two measurements ≥3 months apart) estimated glomerular filtration rate (eGFR) of 60 ml/min per 1.73 m2 or below for persons with baseline eGFR of above 60 ml/min per 1.73 m2 or confirmed 25% decline in eGFR for persons with baseline eGFR of 60 ml/min per 1.73 m2 or less, using the Cockcroft–Gault formula. Poisson regression was used to determine factors associated with CKD.

Results: Two hundred and twenty-five (3.3%) persons progressed to CKD during 21 482 person-years follow-up, an incidence of 1.05 per 100 person-years follow-up [95% confidence interval (CI) 0.91–1.18]; median follow-up was 3.7 years (interquartile range 2.8–5.7). After adjustment for traditional factors associated with CKD and other confounding variables, increasing cumulative exposure to tenofovir [incidence rate ratio (IRR) per year 1.16, 95% CI 1.06–1.25, P < 0.0001), indinavir (IRR 1.12, 95% CI 1.06–1.18, P < 0.0001), atazanavir (IRR 1.21, 95% CI 1.09–1.34, P = 0.0003) and lopinavir/r (IRR 1.08, 95% CI 1.01–1.16, P = 0.030) were associated with a significantly increased rate of CKD. Consistent results were observed in wide-ranging sensitivity analyses, although of marginal statistical significance for lopinavir/r. No other antiretroviral dugs were associated with increased incidence of CKD.

Conclusion: In this nonrandomized large cohort, increasing exposure to tenofovir was associated with a higher incidence of CKD, as was true for indinavir and atazanavir, whereas the results for lopinavir/r were less clear.

aHIV Epidemiology and Biostatistics Group, Research Department of Infection and Population Health, Division of Population Health, University College London Medical School, London, UK

bCopenhagen HIV Programme, Panum Institute, University of Copenhagen, Copenhagen, Denmark

cAcademisch Medisch Centrum bij de Universiteit van Amsterdam, Center for Infection and Immunity Amsterdam and Center for Poverty Related Communicable Diseases, Amsterdam, The Netherlands

dSt Pierre Hospital, Brussels, Belgium

eAIDS Centre, University Hospital, Medical Faculty, Charles University, Plzen, Czech Republic

fDepartment for AIDS Diagnostics and Therapy, Chorzow, Poland

gHospital Clinic i Provincial, Barcelona, Spain

hUniversity Hospital Zürich, University of Zürich, Zürich, Switzerland

iCentre for Viral Disease KMA, Rigshospitalet, Copenhagen, Denmark.

Received 8 February, 2010

Revised 16 March, 2010

Accepted 17 March, 2010

Correspondence to Dr Amanda Mocroft, HIV Epidemiology and Biostatistics Group, Research Department of Infection and Population Health, Division of Population Health, University College London Medical School, Royal Free Campus, Rowland Hill St, London NW3 2PF, UK. Tel: +44 20 7830 2239; fax: +44 20 7794 1224; e-mail:

© 2010 Lippincott Williams & Wilkins, Inc.