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


METHODS
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 >or=3 months apart) estimated glomerular filtration rate (eGFR) of 60 ml/min per 1.73 m or below for persons with baseline eGFR of above 60 ml/min per 1.73 m or confirmed 25% decline in eGFR for persons with baseline eGFR of 60 ml/min per 1.73 m 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 drugs were associated with increased incidence of CKD.


CONCLUSIONS
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.
HIV Epidemiology and Biostatistics Group, Research Department of Infection and Population Health, Division of Population Health, University College London Medical School, Royal Free Campus, London, UK. a.mocroft@ucl.ac.uk
Amanda
A
Mocroft
Ole
O
Kirk
Peter
P
Reiss
Stephane
S
De Wit
Dalibor
D
Sedlacek
Marek
M
Beniowski
Jose
J
Gatell
Andrew N
AN
Phillips
Bruno
B
Ledergerber
Jens D
JD
Lundgren
D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects*; D000069446:Atazanavir Sulfate; D018450:Disease Progression; D004812:Epidemiologic Methods; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006679:HIV Seropositivity / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D015497:HIV-1; D006801:Humans; D019469:Indinavir / Q000009:adverse effects; D007676:Kidney Failure, Chronic / Q000139:chemically induced* / Q000453:epidemiology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000009:adverse effects; D063065:Organophosphonates / Q000009:adverse effects; D011725:Pyridines / Q000009:adverse effects; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects; D000068698:Tenofovir
D019380:Anti-HIV Agents; D009842:Oligopeptides; D063065:Organophosphonates; D011725:Pyridines; D018894:Reverse Transcriptase Inhibitors; D000069446:Atazanavir Sulfate; D019469:Indinavir; D000068698:Tenofovir; D000225:Adenine