[Use of rifampicin plus pyrazinamide for antituberculosis prophylaxis does not increase the risk of severe hepatotoxicity in HIV patients: meta-analysis of randomized controlled clinical trials].

  • Camacho A
  • Pérez-Camacho I
  • Rivero A
 et al. 
  • 17

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Abstract

OBJECTIVE: To compare the incidence of severe hepatitis in HIV-infected patients receiving rifampicin plus pyrazinamide (RZ) for antituberculosis prophylaxis with that of patients receiving a conventional isoniazid-based regime for 6 to 12 months (6-12H).

METHODS: Meta-analysis of randomized controlled trials, in which RZ was compared with 6-12H, the standard regimen for latent tuberculosis infection in HIV-infected patients. A systematic search of studies published between 1986 and 2007 was carried out, and 5 randomized clinical trials conducted in Spain (2), the USA (1), Haiti (1), and Zambia (1) were identified. The absence or presence of severe hepatoxicity, which was defined as toxicity causing the death of the patient or requiring treatment withdrawal, was assessed as a binary response, and the outcome measure was the difference in the risk of hepatotoxicity between patients receiving RZ and those receiving 6-12H (controls).

RESULTS: Among the 5 trials retrieved, 1 was excluded from the final analysis because of incomplete data on the development of hepatotoxicity. A final total of 2657 patients were included (1324 patients receiving RZ and 1333 receiving 6-12H). The development of severe hepatotoxicity was lower in the RZ group than in the 6-12H group (1.208% vs. 2.851%; P=0.0042, 95% CI: -0.028 to -0.005). The meta-analysis showed no statistical evidence of heterogeneity between the studies or publication bias. The difference in the risk of severe hepatotoxicity favored the RZ regimen in both the fixed effects model (-0.0119, 95% CI: -0.0206 to -0.0033) and random effects model (-0.0147, 95% CI: -0.0289 to -0.0006).

CONCLUSIONS: The meta-analysis did not demonstrate an increased risk of severe hepatoxicity in HIV-infected patients receiving tuberculosis prophylaxis with the rifampicin/pyrazinamide combination compared to the conventional 6- or 12-month isoniazid-based regimen.

Author-supplied keywords

  • Anti-HIV Agents
  • Anti-HIV Agents: adverse effects
  • Anti-HIV Agents: therapeutic use
  • Antibiotic Prophylaxis
  • Antitubercular Agents
  • Antitubercular Agents: administration & dosage
  • Antitubercular Agents: adverse effects
  • Antitubercular Agents: therapeutic use
  • Drug Synergism
  • Drug Therapy, Combination
  • Drug-Induced Liver Injury
  • Drug-Induced Liver Injury: epidemiology
  • Drug-Induced Liver Injury: etiology
  • HIV Infections
  • HIV Infections: complications
  • HIV Infections: drug therapy
  • Humans
  • Isoniazid
  • Isoniazid: administration & dosage
  • Isoniazid: adverse effects
  • Isoniazid: therapeutic use
  • Pyrazinamide
  • Pyrazinamide: administration & dosage
  • Pyrazinamide: adverse effects
  • Pyrazinamide: therapeutic use
  • Randomized Controlled Trials as Topic
  • Randomized Controlled Trials as Topic: statistics
  • Risk
  • Tuberculosis
  • Tuberculosis: prevention & control

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Authors

  • Angela Camacho

  • Inés Pérez-Camacho

  • Antonio Rivero

  • Clara Natera

  • Milagros García-Lázaro

  • Juan José Castón

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