Maartens Gary, Decloedt Eric, Cohen Karen
Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Antivir Ther. 2009;14(8):1039-43. doi: 10.3851/IMP1455.
Coadministration of antitubercular and antiretroviral therapy is common in high-burden countries where tuberculosis is the commonest opportunistic infection. Concomitant use of rifampicin and many antiretroviral drugs is complicated by drug-drug interactions caused by the potent induction by rifampicin of genes involved in drug metabolism and transport, which could result in subtherapeutic antiretroviral drug concentrations. This review focuses on drug-drug interactions involving antiretrovirals used in resource-limited settings: the non-nucleoside reverse transcriptase inhibitors (NNRTIs) efavirenz or nevirapine, and ritonavir-boosted protease inhibitors. The reduction of nevirapine concentrations with concomitant rifampicin is greater than with efavirenz, particularly during the lead-in dose period when subtherapeutic concentrations occur in the majority of patients. There is reassuring data on the effectiveness of standard doses of efavirenz with concomitant rifampicin, but the largest cohort study found a higher risk of virological failure with nevirapine. The drug-drug interaction between rifampicin and ritonavir-boosted protease inhibitors is more marked than with the NNRTIs, and therapeutic concentrations have only been achieved with adjusted doses of lopinavir/ritonavir or with saquinavir/ritonavir (400/400 mg every 12 h). The major barrier to using adjusted dose protease inhibitors with rifampicin is the high rates of hepatotoxicity seen in healthy volunteers. The alternative strategy followed in resource-rich settings is to replace rifampicin with rifabutin, but even if the price of rifabutin were to be dramatically reduced it would be difficult to implement in high-burden countries where standardized antitubercular regimens with fixed-dose combinations are used.
在结核病是最常见机会性感染的高负担国家，抗结核治疗与抗逆转录病毒治疗联合使用很常见。利福平与许多抗逆转录病毒药物同时使用时，因利福平对参与药物代谢和转运的基因有强大诱导作用而导致药物相互作用，这可能导致抗逆转录病毒药物浓度低于治疗水平。本综述重点关注资源有限环境中使用的抗逆转录病毒药物之间的药物相互作用：非核苷类逆转录酶抑制剂（NNRTIs）依非韦伦或奈韦拉平，以及利托那韦增强的蛋白酶抑制剂。奈韦拉平与利福平同时使用时浓度降低幅度大于依非韦伦，尤其是在导入剂量期，大多数患者会出现低于治疗水平的浓度。有关于标准剂量依非韦伦与利福平同时使用有效性的确切数据，但最大规模的队列研究发现奈韦拉平病毒学失败风险更高。利福平与利托那韦增强的蛋白酶抑制剂之间的药物相互作用比与NNRTIs更明显，仅通过调整洛匹那韦/利托那韦或沙奎那韦/利托那韦（每12小时400/400毫克）剂量才能达到治疗浓度。使用调整剂量蛋白酶抑制剂与利福平的主要障碍是健康志愿者中出现的高肝毒性发生率。资源丰富环境中采用的替代策略是用利福布汀替代利福平，但即使利福布汀价格大幅降低，在使用固定剂量组合标准化抗结核方案的高负担国家也难以实施。
