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Original article

Glomerular dysfunction and associated risk factors over 4–5 years following antiretroviral therapy initiation in Africa

Wolfgang Stöhr, Andrew Reid, A Sarah Walker, Francis Ssali, Paula Munderi, Ivan Mambule, Cissy Kityo, Heiner Grosskurth, Charles F Gilks, Diana M Gibb, James Hakim, the DART Trial Team

Corresponding author name: Wolfgang Stöhr
Corresponding author e-mail: ws@ctu.mrc.ac.uk

Citation: Antiviral Therapy 2011; 16:1011-1020
doi: 10.3851/IMP1832

Date accepted: 14 February 2011
Date published online: 28 June 2011

Abstract

Background: The aim of this study was to investigate long-term renal function in HIV-infected adults initiating antiretroviral therapy (ART) with a CD4+ T-cell count <200 cells/mm3 in Africa.

Methods: This was an observational analysis within the DART trial randomizing 3,316 adults to routine laboratory and clinical monitoring (LCM) or clinically driven monitoring (CDM). Serum creatinine was measured pre-ART (all ≤360 μmol/l), at weeks 4 and 12, then every 12 weeks for 4–5 years; estimated glomerular filtration rate (eGFR) was determined using the Cockcroft–Gault formula. We analysed eGFR changes, and cumulative incidences of eGFR<30 ml/min/1.73 m2 and chronic kidney disease (CKD; <60 ml/min/1.73 m2 or 25% decrease if <60 ml/min/1.73 m2 pre-ART; confirmed >3 months).

Results: At ART initiation, median CD4+ T-cell count was 86 cells/mm3; 1,492 (45%) participants had mild (60–<90 ml/min/1.73 m2), 237 (7%) moderate (30–<60 ml/min/1.73 m2) and 7 (0.2%) severe (15–<30 ml/min/1.73 m2) decreases in eGFR. First-line ART was zidovudine/lamivudine plus tenofovir (74%), abacavir (9%) or nevirapine (17%). By 4 years, cumulative incidence of eGFR<30 ml/min/1.73 m2 was 2.8% (n=90) and CKD was 5.0% (n=162). Adjusted eGFR increases to 4 years were 1, 9 and 6 ml/min/1.73 m2 with tenofovir, abacavir and nevirapine, respectively (P<0.001), and 4 and 2 ml/min/1.73 m2 for LCM and CDM, respectively (P=0.005; 2 and 3 ml/min/1.73 m2 to 5 years; P=0.81).

Conclusions: On all regimens and monitoring strategies, severe eGFR impairment was infrequent; differences in eGFR changes were small, suggesting that first-line ART, including tenofovir, can be given safely without routine renal function monitoring.

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