[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].
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.
Camacho
Angela
A
Unidad de Gestión Clínica de Enfermedades Infecciosas, Hospital Universitario Reina Sofía, Córdoba, España.
Pérez-Camacho
Inés
I
Rivero
Antonio
A
Natera
Clara
C
García-Lázaro
Milagros
M
Castón
Juan José
JJ
Gallo
Marina
M
Kindelán
José María
JM
Torre-Cisneros
Julián
J
D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use; D019072:Antibiotic Prophylaxis; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology / Q000209:etiology*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011718:Pyrazinamide / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D012306:Risk; D014376:Tuberculosis / Q000517:prevention & control*
D019380:Anti-HIV Agents; D000995:Antitubercular Agents; D011718:Pyrazinamide; D007538:Isoniazid