title: Isoniazid-associated hepatitis and antiretroviral drugs during tuberculosis prophylaxis in hiv-infected adults in Botswana.
abstract: BACKGROUND
  Little is known about the incidence of isoniazid-associated hepatitis in HIV-infected Africans who receive both isoniazid preventive therapy (IPT) and antiretroviral therapy (ART).
  
  
  OBJECTIVE
  To assess the rate of and risk factors for isoniazid (INH)-associated hepatitis in persons living with HIV (PLWH) during IPT.
  
  
  METHODS
  PLWH recruited for a clinical trial received 6 months of open-label, daily, self-administered INH at public health clinics. At screening PLWH were excluded if they had any cough, weight loss, night sweats, or other illness. Alcohol abuse was defined as meeting any CAGE criterion. INH-associated hepatitis (INH-hepatitis) was defined as having either alanine or aspartate aminotransferase greater than 5.0 times the upper limit of normal regardless of symptoms when INH was not excluded as the cause.
  
  
  RESULTS
  Of 1,995 PLWH enrolled between 2004 and 2006, 1,762 adhered to at least 4 months of IPT and were analyzed. Nineteen (1.1%) developed hepatitis probably or possibly associated with INH including one death at month 6; 14 of 19 (74%) occurred in months 1-3. Antiretroviral therapy (ART) was received by 480 participants but was not statistically associated with INH-hepatitis (relative risk [RR], 1.56; 95% confidence intervals [CI], 0.62-3.9); those receiving nevirapine had a higher rate (2.0%) than those receiving efavirenz (0.9%; P = 0.34). Although alcohol use did not reach significance (RR, 1.42; 95% CI, 0.57-3.51), meeting at least one CAGE criterion approached statistical significance (RR, 2.37; 95% CI, 0.96-5.84). Neither age greater than 35 years nor the presence of hepatitis B virus core antibody was associated with INH-hepatitis.
  
  
  CONCLUSIONS
  The observed rates of INH-hepatitis were similar to published data. Six months of IPT, which is recommended by the World Health Organization, was relatively safe in this, the largest cohort of African PLWH. Clinical trial registered with www.clinicaltrials.gov (NCT 00164281).
authors.affiliation: Centers for Disease Control and Prevention, Division of Tuberculosis Elimination, 1600 Clifton Road NE, Mailstop E-10, Atlanta, GA 30333, USA.
authors.forename: Zegabriel
authors.initials: Z
authors.lastname: Tedla
authors.forename: Samba
authors.initials: S
authors.lastname: Nyirenda
authors.forename: Crandall
authors.initials: C
authors.lastname: Peeler
authors.forename: Tefera
authors.initials: T
authors.lastname: Agizew
authors.forename: Thabisa
authors.initials: T
authors.lastname: Sibanda
authors.forename: Oaitse
authors.initials: O
authors.lastname: Motsamai
authors.forename: Andrew
authors.initials: A
authors.lastname: Vernon
authors.forename: Charles D
authors.initials: CD
authors.lastname: Wells
authors.forename: Taraz
authors.initials: T
authors.lastname: Samandari
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000428:Alcohol Drinking / Q000453:epidemiology; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D001902:Botswana / Q000453:epidemiology; D018791:CD4 Lymphocyte Count; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology*; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011322:Primary Prevention; D014376:Tuberculosis / Q000517:prevention & control*
chemical_list: D044966:Anti-Retroviral Agents; D000995:Antitubercular Agents; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D007538:Isoniazid