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A Chronic Kidney Disease Risk Score to Determine Tenofovir Safety in a Prospective Cohort of HIV+ Male Veterans
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Reported by Jules Levin
CROI 2014 March 3-6 Boston, MA
1,2 Rebecca SCHERZER, PhD; 1,3 Monica GANDHI, MD MPH; 4 Michelle M. ESTRELLA, MD; 1,2 Phyllis C. TIEN, MD; 1,3 Steven G. DEEKS, MD; 1,2 Carl GRUNFELD, MD PhD; 1,2 Carmen A. PERALTA, MD; 1,2 Michael G. SHLIPAK, MD MPH
1Author Affiliations: 1 Department of Medicine, University of California, San Francisco, 2 San Francisco VA Medical Center, 3 Positive Health Program, San Francisco General Hospital, 4 School of Medicine, Johns Hopkins University.
Program Abstract:
Background: Tenofovir disoproxil fumarate is a widely used antiretroviral for HIV infection that has been associated with an increased risk of chronic kidney
disease (CKD). Our objective was to derive a scoring system to predict 5-year risk of developing CKD in HIV-infected adults, and to estimate differences in
risk associated with the use of tenofovir.
Methodology: 21,590 HIV-infected men from the Veterans Health Administration aged 18 to 86 years (mean age 47; 54% black) who initiated antiretroviral therapy from 1997-2010 contributed 193,771 years of follow-up. Our outcome was time to first occurrence of CKD, defined as estimated glomerular filtration rate <60ml/min/1.73m2. We developed a point-based score (the VA HIV CKD, or "VHC" risk score) using multivariable Cox proportional hazards models, with weighted point values assigned using regression coefficients from the model.
We assessed traditional kidney risk factors and HIV-related factors for CKD, using stepwise backward selection (significance level of α=0.05) to remove
candidate covariates.
Results: Median follow-up was 6.3 years, during which 2,059 CKD events occurred. The dominant contributors to the VHC risk score were traditional
kidney risk factors (age, glucose, systolic blood pressure, hypertension, triglycerides, proteinuria), although CD4 cell count was also a component. HIV RNA
levels were not associated with increased CKD risk in the final model. The overall 5-year event rate was 7.7% in tenofovir users and 3.8% in non-users
(adjusted HR=2.0, 95%CI: 1.8-2.2). The VHC Cox model identified a progressive increase in the risk of CKD, with 5-year risks in non-users of tenofovir
ranging from <1% ( 0 points) to 16% ( ≥9 points), and risks from 1.4% to 21.4% among tenofovir users. Although hazard ratios for tenofovir were higher
in those with fewer points (HR=2.8 for 0 points, HR=1.3 for ≥9 points), absolute risk and number needed to harm were worst in those with greater points
(NNH=108 for zero points, 20 for ≥9 points). Longer tenofovir exposure was associated with a higher overall 5-year CKD event rate (11.1% for ≥2 years vs.
6.3% for <2 year of exposure), resulting in an NNH [number needed to harm] of 6 in those with ≥2 years and ≥8 points.
Conclusions: The VHC risk score can be used to predict an HIV-infected individual's absolute risk of developing CKD over five years, and may facilitate
clinical decision making around tenofovir use.
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