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Tenofovir Treatment Duration Predicts Proteinuria in a Multiethnic United States Cohort of Children and Adolescents With Perinatal HIV-1 Infection

Purswani, Murli MD*; Patel, Kunjal DSc, MPH†‡; Kopp, Jeffrey B. MD§; Seage, George R. III DSc, MPH†‡; Chernoff, Miriam C. PhD; Hazra, Rohan MD; Siberry, George K. MD, MPH; Mofenson, Lynne M. MD; Scott, Gwendolyn B. MD; Van Dyke, Russell B. MD**for the Pediatric HIVAIDS Cohort Study

The Pediatric Infectious Disease Journal: May 2013 - Volume 32 - Issue 5 - p 495–500
doi: 10.1097/INF.0b013e31827f4eff
HIV Reports

Background: Tenofovir is associated with renal proximal tubule injury. Such toxicity has not been extensively studied in HIV-1–infected children, in whom tenofovir is increasingly used.

Methods: History, urine and blood were collected at regular intervals from 448 children and adolescents with perinatal HIV-1 infection followed in the Pediatric HIV/AIDS Cohort study. Relationships between tenofovir use and proteinuria and chronic kidney disease (CKD) outcomes were examined using multivariable logistic regression models. Proteinuria was defined as at least one urine protein/creatinine ratio (uPCR) ≥0.2, and CKD as ≥2 sequential uPCR ≥0.2 or estimated glomerular filtration rates <60 mL/min/1.73 m2 with no subsequent resolution, or a clinical diagnosis not contradicted by a normal uPCR. Subjects with ≥2 uPCR <0.2, and no abnormal uPCR and eGFR comprised the comparison group.

Results: Subjects were 47% male, 72% black, 24% Hispanic, with entry mean age (±standard deviation) of 11.5 ± 2.5 years. Proteinuria prevalence at entry, and annually during 3 years, ranged from 10.3% to 13.7%. The cumulative prevalence of proteinuria was 22% (94/434, 95% confidence interval: 18%–26%) and CKD 4.5% (20/448, 95% confidence interval: 2.7%–6.8%). Duration of tenofovir use was an independent predictor of proteinuria, with >3 years of exposure having the highest risk compared with no exposure (odds ratio: 2.53, 95% confidence interval: 1.23–5.22, overall P = 0.01). Overall, duration of tenofovir use did not significantly predict the presence of CKD.

Conclusions: Rates of proteinuria and CKD were lower than those seen in the pre–highly active antiretroviral therapy era. However, prolonged exposure to tenofovir increases risk of renal injury.

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From the *Bronx-Lebanon Hospital Center, Albert Einstein College of Medicine, Bronx, NY; Department of Epidemiology, Harvard School of Public Health, Boston, MA; Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA; §Kidney Disease Section, NIDDK, NIH, Bethesda, MD; Pediatric Adolescent Maternal AIDS Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD; Department of Pediatrics, Miller School of Medicine, University of Miami, Miami, FL; and **Tulane University Health Sciences Center, New Orleans, LA.

The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the National Institutes of Health or the Department of Health and Human Services.

The Pediatric HIV/AIDS Cohort Study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development with cofunding from the National Institute on Drug Abuse, the National Institute of Allergy and Infectious Diseases, the Office of AIDS Research, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, the National Institute on Deafness and Other Communication Disorders, the National Heart Lung and Blood Institute, the National Institute of Dental and Craniofacial Research and the National Institute on Alcohol Abuse and Alcoholism, through cooperative agreements with the Harvard University School of Public Health (HD052102, 3U01HD052102-05S1, 3U01HD052102-06S3) and the Tulane University School of Medicine (HD052104, 3U01HD052104-06S1). The authors have no other funding or conflicts of interest to disclose.

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Address for correspondence: Murli Purswani, MD, Albert Einstein College of Medicine, Bronx Lebanon Hospital Center, 1650 Selwyn Ave, Bronx, NY 10457. E-mail:

© 2013 Lippincott Williams & Wilkins, Inc.