McIlleron Helen, Meintjes Graeme, Burman William J, Maartens Gary
Division of Clinical Pharmacology, University of Cape Town, Cape Town, South Africa.
J Infect Dis. 2007 Aug 15;196 Suppl 1:S63-75. doi: 10.1086/518655.
Access to antiretroviral therapy is rapidly expanding in resource-limited settings, where tuberculosis is the most common opportunistic infection. Coadministration of antitubercular and antiretroviral agents is, therefore, occurring commonly, and it is associated with 3 major complications. First, induction of cytochrome P-450 enzymes and P-glycoprotein by rifampin results in reduced concentrations of nonnucleoside reverse-transcriptase inhibitors and, particularly, protease inhibitors. This potentially results in the loss of antiviral efficacy and the development of viral resistance. Replacing rifampin with rifabutin, which does not significantly affect the concentrations of antiretroviral agents, is advocated but is currently unaffordable in resource-limited settings. Second, overlapping toxicities of antitubercular and antiretroviral agents occur frequently, necessitating discontinuation of therapy and increasing the risk of nonadherence. Third, immunopathological reactions, termed "the immune reconstitution inflammatory syndrome," occur frequently when antiretroviral therapy is initiated in patients with tuberculosis. These complexities of coadministration of antitubercular and antiretroviral agents are reviewed, and research priorities are highlighted.
在资源有限的地区，抗逆转录病毒疗法的可及性正在迅速扩大，而在这些地区，结核病是最常见的机会性感染。因此，抗结核药物和抗逆转录病毒药物的联合使用很常见，且与三大主要并发症相关。首先，利福平诱导细胞色素P-450酶和P-糖蛋白，导致非核苷类逆转录酶抑制剂尤其是蛋白酶抑制剂的浓度降低。这可能导致抗病毒疗效丧失和病毒耐药性的产生。有人主张用对抗逆转录病毒药物浓度无显著影响的利福布汀替代利福平，但目前在资源有限的地区这一做法费用过高。其次，抗结核药物和抗逆转录病毒药物的毒性重叠经常发生，这就需要中断治疗，并增加了不坚持治疗的风险。第三，在结核病患者中开始抗逆转录病毒治疗时，经常会出现被称为“免疫重建炎症综合征”的免疫病理反应。本文对抗结核药物和抗逆转录病毒药物联合使用的这些复杂性进行了综述，并突出了研究重点。
