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

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Abstract
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 2 with no subsequent resolution, or a clinical diagnosis not contradicted by a normal uPCR. Subjects with ≥2 uPCR 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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