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利福平与抗逆转录病毒药物之间的药理相互作用:资源有限环境下的挑战与研究重点

Pharmacological interactions between rifampicin and antiretroviral drugs: challenges and research priorities for resource-limited settings.

作者信息

Semvua Hadija H, Kibiki Gibson S, Kisanga Elton R, Boeree Martin J, Burger David M, Aarnoutse Rob

机构信息

*Kilimanjaro Clinical Research Institute, Kilimanjaro Christian Medical Centre, Moshi, Tanzania; †University Centre for Chronic Diseases Dekkerswald, Radboud University Medical Centre, Nijmegen, the Netherlands; and ‡Department of Pharmacy, Radboud University Medical Centre, Nijmegen, the Netherlands.

出版信息

Ther Drug Monit. 2015 Feb;37(1):22-32. doi: 10.1097/FTD.0000000000000108.

Abstract

Coadministration of antituberculosis and antiretroviral therapy is often inevitable in high-burden countries where tuberculosis (TB) is the most common opportunistic infection associated with HIV/AIDS. Concurrent use of rifampicin and many antiretroviral drugs is complicated by pharmacokinetic drug-drug interactions. Rifampicin is a very potent enzyme inducer, which can result in subtherapeutic antiretroviral drug concentrations. In addition, TB drugs and antiretroviral drugs have additive (pharmacodynamic) interactions as reflected in overlapping adverse effect profiles. This review provides an overview of the pharmacological interactions between rifampicin-based TB treatment and antiretroviral drugs in adults living in resource-limited settings. Major progress has been made to evaluate the interactions between TB drugs and antiretroviral therapy; however, burning questions remain concerning nevirapine and efavirenz effectiveness during rifampicin-based TB treatment, treatment options for TB-HIV-coinfected patients with nonnucleoside reverse transcriptase inhibitor resistance or intolerance, and exact treatment or dosing schedules for vulnerable patients including children and pregnant women. The current research priorities can be addressed by maximizing the use of already existing data, creating new data by conducting clinical trials and prospective observational studies and to engage a lobby to make currently unavailable drugs available to those most in need.

摘要

在结核病(TB)是与艾滋病毒/艾滋病相关的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的联合使用往往不可避免。利福平与许多抗逆转录病毒药物同时使用时,会因药代动力学药物相互作用而变得复杂。利福平是一种非常强效的酶诱导剂,可导致抗逆转录病毒药物浓度低于治疗水平。此外,抗结核药物和抗逆转录病毒药物存在相加(药效学)相互作用,这在重叠的不良反应谱中有所体现。本综述概述了资源有限环境下成人中基于利福平的抗结核治疗与抗逆转录病毒药物之间的药理相互作用。在评估抗结核药物与抗逆转录病毒治疗之间的相互作用方面已取得重大进展;然而,关于基于利福平的抗结核治疗期间奈韦拉平和依非韦伦的有效性、对非核苷类逆转录酶抑制剂耐药或不耐受的结核-艾滋病毒合并感染患者的治疗选择,以及包括儿童和孕妇在内的脆弱患者的确切治疗或给药方案等紧迫问题仍然存在。目前的研究重点可以通过最大限度地利用现有数据、通过开展临床试验和前瞻性观察性研究来创建新数据,以及争取游说以使目前无法获得的药物能够提供给最有需要的人来解决。

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