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

Scherzer, Rebeccaa,b; Gandhi, Monicaa,c; Estrella, Michelle M.d; Tien, Phyllis C.a,b; Deeks, Steven G.a,c; Grunfeld, Carla,b; Peralta, Carmen A.a,b; Shlipak, Michael G.a,b

doi: 10.1097/QAD.0000000000000258
Clinical Science

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 1.73 m2) 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.

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aDepartment of Medicine, University of California, San Francisco

bSan Francisco VA Medical Center

cPositive Health Program, San Francisco General Hospital, San Francisco, California

dSchool of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.

Correspondence to Michael G. Shlipak, MD, MPH, San Francisco Veterans Affairs Medical Center, Box 111A1, 4150 Clement Street, San Francisco, CA 94121, USA. Tel: +1 415 750 2093; fax: +1 415 750 3179; e-mail:

Received 13 January, 2014

Revised 6 February, 2014

Accepted 6 February, 2014

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© 2014 Lippincott Williams & Wilkins, Inc.