Hepatotoxicity of rifampin and pyrazinamide in the treatment of latent tuberculosis infection in HIV-infected persons: Is it different than in HIV-uninfected persons?

Background. In 2000, results of a multinational trial demonstrated that a 2-month course of rifampin and pyrazinamide (RZ) was as effective as isoniazid (INH) in reducing tuberculosis in human immunodeficiency virus (HIV)-infected individuals with latent tuberculosis infection (LTBI). After the release of new guidelines, the Centers for Disease Control and Prevention received reports of severe hepatotoxicity associated with the use of the RZ regimen for the treatment of LTBI in the general population. To better understand the occurrence of hepatotoxicity in an HIV-infected population, we conducted a more detailed analysis of the liver function test results obtained in the multinational trial of RZ. Methods. At study entry, patients were required to have a bilirubin level of less than or equal to2.5 mg/dL and both an aspartate aminotransferase (AST) level and an alkaline phosphatase level of less than or equal to5 times the upper limit of normal. Patients with acute hepatitis were excluded. At months 1 and 2 of the study, all patients had bilirubin and AST levels measured. Results. There was no difference between the RZ and INH groups with regard to AST level or bilirubin level at baseline. An increase in the AST level of greater than or equal to40 U/L was associated with the use of INH and older age; and an increase in the bilirubin level of greater than or equal to0.5 mg/dL was associated with the use of RZ, male sex, and nonwhite race (P < .05). An absolute AST level of >250 U/L occurred in 12 of 745 INH recipients and in 15 of 721 RZ recipients (P = .56), and an absolute bilirubin level of >2.5 mg/dL occurred in 5 of 743 INH recipients and 13 of 718 RZ recipients (P = .06). Conclusions. These data demonstrate very little liver injury associated with either INH or RZ in the HIV-infected subjects, leaving unclear the reasons for serious RZ-related liver damage in the general population.