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.

BACKGROUND AND OBJECTIVE: 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. METHODS: We reviewed hepatotoxicity cases among non-HIV-infected individuals and HIV-infected pregnant women and their offspring receiving short- (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. RESULTS: 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). CONCLUSIONS: 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.

Racial variations in care and outcomes for inpatient HIV-related pneumocystis pneumonia.

Racial disparities in HIV-care include the disproportionate impact of HIV/AIDS on African Americans. We conducted a retrospective review of 1,855 cases at 78 hospitals in nine cities to evaluate racial variations in inpatient care for AIDS-related Pneumocystis pneumonia (PCP) shortly after the introduction of highly active anti-retroviral therapies. While inpatient HIV-related PCP mortality was comparable between Whites and Hispanics (p=0.94), African Americans were less likely than Whites to die in-hospital (AOR 0.69, 95% CI 0.48, 0.99) and more likely to receive timely anti-PCP medications (AOR 1.67, 95% CI 1.21, 2.30) and timely corticosteroids (AOR 1.46, 95% CI 1.17, 1.82). Findings were compared with those from our study involving 1,547 patients at 82 hospitals in five cities over the first decade of the AIDS epidemic. In contrast to the first study, in the second decade African Americans were more likely to receive timely and appropriate therapy for HIV-related PCP, and resultantly were more likely to survive the hospitalization.