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Background:  Serious symptomatic hepatotoxicity has been associated with nevirapine (NVP) use in HIV-infected adults; because of this toxicity, alternative treatments in females and adults with higher CD4 counts may be advisable. However, in HIV-infected children, ART options are limited due to the lack of age appropriate formulations. NVP is available as a liquid, and thus important in the treatment of children. We wanted to determine if similar hepatotoxicity has been described in the pediatric population as in adults.

Methods:  We reviewed scientific literature using PubMed with the search terms, pediatrics, children, HIV, NVP, ages 0 to 18 yrs, treatment, and ART; FDA Adverse Event Reporting System (AERS) database using the search terms NVP, liver adverse events, and age < 18 years; and the Medical Officer Review of NDA 20-933 for NVP oral solution. All AERS/literature data were reviewed by 2 or 3 people and all duplicates identified were removed by comparing study, age, weight, date of birth, date of adverse event, reporting source, and clinical course. The following were excluded from the analysis: single dose NVP for perinatal mother-to-child transmission, neonatal jaundice, hepatomegaly as only adverse events, hepatitis C virus (HCV), hepatitis B virus (HBV), and gall bladder disease.

Results:  A total of 779 children exposed to NVP were identified via the scientific literature (437 patients, 14 articles) and NDA review (342 patients). Children ranged in age from 6 weeks to 19 years. The majority acquired HIV perinatally. The median CD4% ranged from 10.5 to 13.5%. Hepatotoxicity was reported in 21/779, (2.7%) and included ­LFTs (13), hepatic failure (3), ­GGT (3), and hyperbilirubinemia (2). None of the 3 cases of hepatic failure were attributed to NVP. An additional 4 AERS reports of liver adverse events in pediatric patients were identified (3 hepatitis, 1 increased LFTs); the only hepatic adverse event attributed to NVP was a report of a 17-year-old male with fulminant hepatitis 7 days after starting NVP. 

Conclusions:  On review of 783 HIV-infected pediatric patients, there was one case of fulminant hepatitis similar to that seen in adults, which was reported in a 17-year-old. There was no evidence of a serious clinical hepatic event associated with NVP use in any child prior to adolescence. The reason for this is unclear and may be due to the advanced study populations studies with lower CD4 counts, differences in pediatric and adult immunity, or lack of reporting.

Keywords: nevirapine; hepatotoxicity; pediatrics