A chronic kidney disease risk score to determine tenofovir safety in a prospective cohort of HIV-positive male veterans

Objective: 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 individuals and to estimate difference in risk associated with tenofovir use. Design: We evaluated time to first occurrence of CKD (estimated glomerular filtration rate <60 ml/min per 1.73m2) in 21 590 HIV-infected men from the Veterans Health Administration initiating antiretroviral therapy from 1997 to 2010. Methods: We developed a point-based score using multivariable Cox regression models. Median follow-up was 6.3 years, during which 2059 CKD events occurred. Results: Dominant contributors to the CKD risk score were traditional kidney risk factors (age, glucose, SBP, hypertension, triglycerides, proteinuria); CD4⁺ cell count was also a component, but not HIV RNA. The overall 5-year event rate was 7.7% in tenofovir users and 3.8% in nonusers [overall adjusted hazard ratio 2.0, 95% confidence interval (CI) 1.8-2.2]. There was a progressive increase in 5-year CKD risk, ranging from less than 1% (zero points) to 16% (≥9 points) in nonusers of tenofovir, and from 1.4 to 21.4% among tenofovir users. The estimated number-needed-to-harm (NNH) for tenofovir use ranged from 108 for those with zero points to 20 for persons with at least nine points. Among tenofovir users with at least 1 year exposure, NNH ranged from 68 (zero points) to five (≥9 points). Conclusion: The CKD risk score can be used to predict an HIV-infected individual's absolute risk of developing CKD over 5 years and may facilitate clinical decision-making around tenofovir use.