title: 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.
abstract: 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=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.
  
  
  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.
authors.affiliation: Department of Medicine, Northwestern University Feinberg School of Medicine, and Department of Pharmacy, Northwestern Memorial Hospital, Chicago, Illinois 60611, USA. j-mckoy@northwestern.edu
authors.forename: June M
authors.initials: JM
authors.lastname: McKoy
authors.forename: Charles L
authors.initials: CL
authors.lastname: Bennett
authors.forename: Marc H
authors.initials: MH
authors.lastname: Scheetz
authors.forename: Virginia
authors.initials: V
authors.lastname: Differding
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Chandler
authors.forename: Kimberly K
authors.initials: KK
authors.lastname: Scarsi
authors.forename: Paul R
authors.initials: PR
authors.lastname: Yarnold
authors.forename: Sarah
authors.initials: S
authors.lastname: Sutton
authors.forename: Frank
authors.initials: F
authors.lastname: Palella
authors.forename: Stuart
authors.initials: S
authors.lastname: Johnson
authors.forename: Eniola
authors.initials: E
authors.lastname: Obadina
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Raisch
authors.forename: Jorge P
authors.initials: JP
authors.lastname: Parada
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D056486:Chemical and Drug Induced Liver Injury / Q000151:congenital / Q000453:epidemiology*; D003627:Data Interpretation, Statistical; D005260:Female; D015658:HIV Infections / Q000151:congenital / Q000517:prevention & control* / Q000635:transmission*; D006801:Humans; D007231:Infant, Newborn; D019829:Nevirapine / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D011247:Pregnancy; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D014481:United States / Q000453:epidemiology; D014486:United States Food and Drug Administration
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine