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Tenofovir treatment duration predicts proteinuria in a multiethnic United States Cohort of children and adolescents with perinatal HIV-1 infection.

ABSTRACT: 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.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 m 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.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.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.

SUBMITTER: Purswani M

PROVIDER: S-EPMC3800277 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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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 M Patel Kunjal K Kopp Jeffrey B JB Seage George R GR Chernoff Miriam C MC Hazra Rohan R Siberry George K GK Mofenson Lynne M LM Scott Gwendolyn B GB Van Dyke Russell B RB

The Pediatric infectious disease journal 20130501 5

<h4>Background</h4>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.<h4>Methods</h4>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 mul ...[more]

PMID: 23249917

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Project description:Adolescents and young adults aged <25 are a key population in the HIV epidemic, with very high HIV incidence rates in many geographic settings and a large number who have limited access to prevention services. Thus, any biomedical HIV prevention approach should prepare licensure and implementation strategies for young populations. Oral pre-exposure prophylaxis (PrEP) is the first antiretroviral-based prevention intervention with proven efficacy across many settings and populations, and regulatory and policy approvals at global and national levels are occurring rapidly. We discuss available data from studies in the United States and South Africa on the use of oral PrEP for HIV prevention in adolescent minors, along with some of the implementation challenges.Ongoing studies in the United States and South Africa among youth under the age of 18 should provide the safety data needed by the end of 2016 to contribute to licensure of Truvada as daily PrEP in adolescents. The challenges of completing these studies as well as foreseeable broader challenges highlighted by this work are presented. Adherence to daily PrEP is a greater challenge for younger populations, and poor adherence was associated with decreased efficacy in all PrEP trials. Individual-level barriers include limited familiarity with antiretroviral-based prevention, stigma, product storage, and social support. Structural challenges include healthcare financing for PrEP, clinician acceptability and comfort with PrEP delivery, and the limited youth-friendly health services available. These challenges are discussed in the context of the work done to date in the United States and South Africa, but will likely be magnified in the setting of limited resources in many other countries that are heavily impacted by HIV.Adolescent populations are particularly vulnerable to HIV, and oral PrEP in these populations is likely to have an impact on population-level HIV incidence. The challenges of disseminating an HIV biomedical prevention tool requiring daily usage in adolescents are formidable, but addressing these issues and starting dialogues will lay the groundwork for the many other HIV prevention tools now being developed and tested.

Dataset Information

Tenofovir treatment duration predicts proteinuria in a multiethnic United States Cohort of children and adolescents with perinatal HIV-1 infection.

Publications

Tenofovir treatment duration predicts proteinuria in a multiethnic United States Cohort of children and adolescents with perinatal HIV-1 infection.

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