Hepatotoxicity Associated with Long-versus Short-Course HIV-Prophylactic Nevirapine Use: A Systematic Review and Meta-Analysis from the Research on Adverse Drug events And Reports (RADAR) Project

Department of Medicine, Northwestern University Feinberg School of Medicine, and Department of Pharmacy, Northwestern Memorial Hospital, Chicago, Illinois 60611, USA.
Drug Safety (Impact Factor: 2.82). 02/2009; 32(2):147-58.
Source: PubMed


The antiretroviral nevirapine can cause severe hepatotoxicity when used 'off-label' for preventing mother-to-child HIV transmission (PMTCT), newborn post-exposure prophylaxis and for pre- and post-exposure prophylaxis among non-HIV-infected individuals. We describe the incidence of hepatotoxicity with short- versus long-course nevirapine-containing regimens in these groups.
We reviewed hepatotoxicity cases among non-HIV-infected individuals and HIV-infected pregnant women and their offspring receiving short- (<or=4 days) versus long-course (>or=5 days) nevirapine prophylaxis. Sources included adverse event reports from pharmaceutical manufacturers and the US FDA, reports from peer-reviewed journals/scientific meetings and the Research on Adverse Drug events And Reports (RADAR) project. Hepatotoxicity was scored using the AIDS Clinical Trial Group criteria.
Toxicity data for 8216 patients treated with nevirapine-containing regimens were reviewed. Among 402 non-HIV-infected individuals receiving short- (n=251) or long-course (n=151) nevirapine, rates of grade 1-2 hepatotoxicity were 1.99% versus 5.30%, respectively, and rates of grade 3-4 hepatotoxicity were 0.00% versus 13.25%, respectively (p<0.001 for both comparisons). Among 4740 HIV-infected pregnant women receiving short- (n=3031) versus long-course (n=1709) nevirapine, rates of grade 1-2 hepatotoxicity were 0.62% and 7.04%, respectively, and rates of grade 3-4 hepatotoxicity were 0.23% versus 4.39%, respectively (p<0.001 for both comparisons). The rates of grade 3-4 hepatotoxicity among 3074 neonates of nevirapine-exposed HIV-infected pregnant women were 0.8% for those receiving short-course (n=2801) versus 1.1% for those receiving long-course (n=273) therapy (p<0.72).
Therapy duration appears to significantly predict nevirapine hepatotoxicity. Short-course nevirapine for HIV prophylaxis is associated with fewer hepatotoxic reactions for non-HIV-infected individuals or pregnant HIV-infected women and their offspring, but administration of prophylactic nevirapine for >or=2 weeks appears to be associated with high rates of hepatotoxicity among non-HIV-infected individuals and HIV-infected pregnant mothers. When full highly active antiretroviral therapy (HAART) regimens are not available, single-dose nevirapine plus short-course nucleoside reverse transcriptase inhibitors to decrease the development of HIV viral resistance is an essential therapeutic option for PMTCT and these data support the safety of single-dose nevirapine in this setting.

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    • "Hepatotoxicity is a major adverse event associated with both HIV and TB therapy, and monitoring for DILI is critically important in the care of these patients. Hepatotoxicity rates associated with nevirapine-based HIV therapy (widely used in the developing world, including our study site) can exceed 13%, depending on treatment course and underlying risk factors [2], [23], [24]. The overall incidence of clinically relevant hepatotoxicity on TB therapy (typically due to isoniazid, rifampin, and/or pyrazinamide) ranges from 2 to 33%, and risk may be increased by multiple factors, including hepatitis (B and/or C), alcohol use, and increasing age [1], [25]. "
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    • "Nevirapine (NVP) is a nonnucleoside reverse transcriptase inhibitor (NNRTI) used for the prophylaxis and treatment of human immunodeficiency virus (HIV) infections. Unfortunately , NVP is associated with severe skin and hepatic hypersensitivity reactions that have hampered its use particularly for HIV prophylaxis [1]. The hepatotoxicity is common in patients with higher CD4 counts and in the first three weeks of NVP treatment [2] [3]. "
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