Association of tenofovir exposure with kidney disease risk in HIV infection.
OBJECTIVE
Despite widespread HAART use, HIV disease remains associated with increased risk of kidney disease. Whether tenofovir use is associated with higher risk of kidney disease is controversial.


METHODS
We evaluated the association of cumulative and ever exposure to tenofovir on kidney outcomes in 10,841 HIV-infected patients from the Veterans Health Administration who initiated antiretroviral therapy from 1997 to 2007.


METHODS
Cox proportional hazards and marginal structural models evaluated associations between tenofovir and time to first occurrence of proteinuria (two consecutive urine dipstick measurements ≥30 mg/dl), rapid decline in kidney function (≥3 ml/min per 1.73 m annual decline), and chronic kidney disease (CKD; estimated glomerular filtration rate <60 ml/min per 1.73 m).


RESULTS
Median follow-up ranged from 3.9 years (proteinuria) to 5.5 years (CKD), during which 3400 proteinuria, 3078 rapid decline, and 533 CKD events occurred. After multivariable adjustment, each year of exposure to tenofovir was associated with 34% increased risk of proteinuria [95% confidence interval (CI) 25-45, P < 0.0001], 11% increased risk of rapid decline (3-18, P = 0.0033), and 33% increased risk of CKD (18-51, P < 0.0001). Preexisting renal risk factors did not appear to worsen the effects of tenofovir. Other antiretroviral drugs showed weaker or inconsistent associations with kidney disease events. Among those who discontinued tenofovir use, risk of kidney disease events did not appear to decrease during follow-up.


CONCLUSIONS
Tenofovir exposure was independently associated with increased risk for three types of kidney disease events, and did not appear to be reversible. Because subtle kidney function decline affects long-term morbidity and mortality, the balance between efficacy and probable adverse effects requires further study.
Department of Medicine, San Francisco Veterans Affairs Medical Center, California, USA.
Rebecca
R
Scherzer
Michelle
M
Estrella
Yongmei
Y
Li
Andy I
AI
Choi
Steven G
SG
Deeks
Carl
C
Grunfeld
Michael G
MG
Shlipak
D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives*; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000139:chemically induced* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000009:adverse effects*; D011507:Proteinuria / Q000139:chemically induced*; D012307:Risk Factors; D000068698:Tenofovir; D013997:Time Factors; D016896:Treatment Outcome
D019380:Anti-HIV Agents; D063065:Organophosphonates; D000068698:Tenofovir; D000225:Adenine