Department of Medicine, Imperial College London, London, UK.
Department of HIV Medicine, Chelsea and Westminster Hospital, London, UK.
J Int AIDS Soc. 2019 Jul;22(7):e25333. doi: 10.1002/jia2.25333.
Rifabutin, a rifamycin of equivalent potency to rifampicin, has several advantages in its pharmacokinetic and toxicity profile, particularly in HIV co-infected patients on combined antiretroviral therapy (cART). In this commentary, we evaluate evidence supporting increased global use of rifabutin and highlight key recommendations for action.
Although extrapolation of data from HIV uninfected patients would suggest non-inferiority, there has been no randomized controlled study comparing rifabutin versus rifampicin in the outcomes of relapse-free cure, in drug susceptible tuberculosis (TB), in HIV co-infected patients on currently utilized cART regimens or in paediatric populations. An important advantage of rifabutin is that compared to the dose adjustments required with rifampicin, it can be co-administered with the integrase strand transfer inhibitors raltegravir or dolutegravir without the need for dose adjustments. This strategy would be easier to implement in a programmatic setting and would save costs. We have assessed cost incentives to utilize rifabutin and have estimated generic costs for a range of rifabutin dosage scenarios. Where facilities are present for drug re-challenge and monitoring for drug toxicity and cross-reactivity, rifabutin offers a switch alternative for adverse drug reactions (ADR)s attributed to rifampicin. This would negate the need to prolong treatment in the absence of a rifamycin as part of short-course multidrug therapy. There is evidence of incomplete cross-resistance to rifampicin and rifabutin. Rifabutin may be useful in rifampicin-resistant TB, in an estimated 20% of cases, based on phenotypic or genotypic rifabutin susceptibility testing.
Rifabutin should be available globally as a first-line rifamycin in HIV co-infected individuals and as a switch option in cases of rifampicin associated ADRs. Further studies are needed to ascertain the utility of rifabutin in rifampicin-resistant rifabutin-susceptible TB.
利福布丁是一种与利福平等效的利福霉素，在药代动力学和毒性特征方面具有多项优势，特别是在接受联合抗逆转录病毒疗法（cART）的 HIV 合并感染患者中。在本评论中，我们评估了支持增加全球范围内使用利福布丁的证据，并强调了关键的行动建议。
尽管从未感染 HIV 的患者中得出的数据推断表明其非劣效性，但尚无随机对照研究比较利福布丁与利福平在无复发生存治愈、药物敏感型结核病（TB）、接受当前 cART 方案治疗的 HIV 合并感染患者或儿科人群中的疗效。利福布丁的一个重要优势是，与利福平所需的剂量调整相比，它可以与整合酶链转移抑制剂拉替拉韦或多替拉韦联合使用，而无需调整剂量。这种策略在规划环境中更容易实施，并可以节省成本。我们评估了使用利福布丁的成本激励因素，并估计了一系列利福布丁剂量方案的通用成本。在有条件进行药物再挑战和监测药物毒性及交叉反应的情况下，利福布丁为因利福平引起的药物不良反应（ADR）提供了替代方案。这将避免在缺乏利福霉素的情况下需要延长治疗时间，作为短程多药治疗的一部分。有证据表明，对利福平的不完全交叉耐药性，利福布丁可能对估计有 20%的利福平耐药性 TB 有用，这是基于表型或基因型利福布丁药敏试验。
利福布丁应作为 HIV 合并感染个体的一线利福霉素，以及利福平相关 ADR 的替代方案，在全球范围内提供。需要进一步研究以确定利福布丁在利福平耐药性利福布丁敏感型 TB 中的应用价值。
