Glomerular dysfunction and associated risk factors over 4-5 years following antiretroviral therapy initiation in Africa.
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.
MRC Clinical Trials Unit, London, UK. ws@ctu.mrc.ac.uk
Wolfgang
W
Stöhr
Andrew
A
Reid
A Sarah
AS
Walker
Francis
F
Ssali
Paula
P
Munderi
Ivan
I
Mambule
Cissy
C
Kityo
Heiner
H
Grosskurth
Charles F
CF
Gilks
Diana M
DM
Gibb
James
J
Hakim
D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000328:Adult; D000349:Africa; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D018791:CD4 Lymphocyte Count; D003404:Creatinine / Q000097:blood; D015224:Dideoxynucleosides / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005919:Glomerular Filtration Rate; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007674:Kidney Diseases / Q000150:complications / Q000453:epidemiology*; D007678:Kidney Glomerulus / Q000503:physiopathology*; D019259:Lamivudine / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D019829:Nevirapine / Q000008:administration & dosage / Q000009:adverse effects; D063065:Organophosphonates / Q000008:administration & dosage / Q000009:adverse effects; D012307:Risk Factors; D000068698:Tenofovir; D013997:Time Factors; D015215:Zidovudine / Q000008:administration & dosage / Q000009:adverse effects; D000099227:Abacavir
D000225:Adenine; D003404:Creatinine; D015224:Dideoxynucleosides; D019259:Lamivudine; D019829:Nevirapine; D063065:Organophosphonates; D000068698:Tenofovir; D015215:Zidovudine; D000099227:Abacavir