Camacho Angela, Pérez-Camacho Inés, Rivero Antonio, Natera Clara, García-Lázaro Milagros, Castón Juan José, Gallo Marina, Kindelán José María, Torre-Cisneros Julián
Unidad de Gestión Clínica de Enfermedades Infecciosas, Hospital Universitario Reina Sofía, Córdoba, España.
Enferm Infecc Microbiol Clin. 2010 Apr;28(4):239-44. doi: 10.1016/j.eimc.2009.04.003. Epub 2009 Aug 3.
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).
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).
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).
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.
比较接受利福平加吡嗪酰胺（RZ）进行抗结核预防的HIV感染患者与接受基于异烟肼的传统方案治疗6至12个月（6 - 12H）的患者中严重肝炎的发生率。
对随机对照试验进行荟萃分析，其中将RZ与6 - 12H（HIV感染患者潜伏性结核感染的标准方案）进行比较。对1986年至2007年发表的研究进行系统检索，确定了在西班牙（2项）、美国（1项）、海地（1项）和赞比亚（1项）进行的5项随机临床试验。将严重肝毒性（定义为导致患者死亡或需要停药的毒性）的有无作为二元反应进行评估，结果指标是接受RZ的患者与接受6 - 12H（对照）的患者之间肝毒性风险的差异。
在检索到的5项试验中，1项因肝毒性发生情况的数据不完整而被排除在最终分析之外。最终共纳入2657例患者（1324例接受RZ，1333例接受6 - 12H）。RZ组严重肝毒性的发生率低于6 - 12H组（1.208%对2.851%；P = 0.0042，95%CI： - 0.028至 - 0.005）。荟萃分析显示各研究之间无统计学异质性证据或发表偏倚。在固定效应模型（ - 0.0119，95%CI： - 0.0206至 - 0.0033）和随机效应模型（ - 0.0147，95%CI： - 0.0289至 - 0.0006）中，严重肝毒性风险的差异均有利于RZ方案。
荟萃分析未表明与传统的6个月或12个月基于异烟肼的方案相比，接受利福平/吡嗪酰胺组合进行结核预防的HIV感染患者发生严重肝毒性的风险增加。
