title: Hepatotoxicity in an African antiretroviral therapy cohort: the effect of tuberculosis and hepatitis B.
abstract: OBJECTIVE
  Hepatotoxicity is a significant complication of antiretroviral therapy (ART). We assessed the incidence of and risk factors for hepatotoxicity among HIV-infected individuals on ART in South Africa.
  
  
  METHODS
  We conducted a retrospective cohort study in a workplace HIV care program in South Africa which uses a first-line regimen of efavirenz, zidovudine, and lamivudine and provides routine clinical and laboratory monitoring.
  
  
  METHODS
  We included subjects with baseline and follow-up alanine transaminase and aspartate aminotransferase tests. Severe hepatotoxicity cases were identified during the first 12 months of ART. Potential risk factors, including concomitant medication use, tuberculosis, and hepatitis B and C, were determined from clinical records, database queries, and serological testing. Associations with hepatotoxicity were investigated using Cox proportional hazards modeling.
  
  
  RESULTS
  Of the 868 subjects (94% male, median age 41 years), the median nadir CD4 cell count was 136/microl, 25% received concomitant tuberculosis treatment during ART, and 17% of a randomly selected subset were positive for hepatitis B surface antigen (HBsAg). We identified 7.7 episodes of severe hepatotoxicity per 100 person-years. Tuberculosis treatment increased risk 8.5 fold, positive HBsAg 3.0 fold, and nadir CD4 cells count < 100/microl 1.9 fold. Importantly, the fraction of patients with severe hepatotoxicity on ART (4.6%) was similar to the fraction with liver enzyme elevations > 5 times the upper limit of normal before starting ART (4%).
  
  
  CONCLUSIONS
  In this African ART cohort, we found a low incidence of and minimal morbidity due to hepatotoxicity. HBsAg and concomitant tuberculosis therapy significantly increased the risk of hepatotoxicity.
authors.affiliation: Aurum Institute for Health Research, Johannesburg, South Africa. choffmann@jhmi.edu
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Hoffmann
authors.forename: Salome
authors.initials: S
authors.lastname: Charalambous
authors.forename: Chloe L
authors.initials: CL
authors.lastname: Thio
authors.forename: Desmond J
authors.initials: DJ
authors.lastname: Martin
authors.forename: Lindiwe
authors.initials: L
authors.lastname: Pemba
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Fielding
authors.forename: Gavin J
authors.initials: GJ
authors.lastname: Churchyard
authors.forename: Richard E
authors.initials: RE
authors.lastname: Chaisson
authors.forename: Alison D
authors.initials: AD
authors.lastname: Grant
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000032:analysis; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000995:Antitubercular Agents / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000032:analysis; D056486:Chemical and Drug Induced Liver Injury; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D006509:Hepatitis B / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006801:Humans; D015994:Incidence; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009784:Occupational Diseases / Q000188:drug therapy / Q000453:epidemiology / Q000276:immunology; D012189:Retrospective Studies; D013019:South Africa / Q000453:epidemiology; D016896:Treatment Outcome; D014376:Tuberculosis / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology
chemical_list: D019380:Anti-HIV Agents; D000995:Antitubercular Agents; D006514:Hepatitis B Surface Antigens; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase