Kakuda Thomas N, Crauwels Herta, Opsomer Magda, Tomaka Frank, van de Casteele Tom, Vanveggel Simon, Iterbeke Koen, de Smedt Goedele
Janssen Pharmaceutics, LLC, Titusville, NJ, USA.
Expert Rev Anti Infect Ther. 2015 Jun;13(6):691-704. doi: 10.1586/14787210.2015.1033400.
A current focus in HIV management is improving adherence by minimizing pill burden with convenient formulations, including fixed-dose combinations (FDCs). Darunavir, a HIV protease inhibitor, co-administered with low-dose ritonavir (800/100 mg once daily), is recommended in guidelines in combination with other antiretrovirals for HIV patients with no darunavir resistance-associated mutations. Cobicistat is an alternative agent to ritonavir for boosting plasma drug levels of darunavir among other antiretrovirals. Cobicistat is a more specific cytochrome P450 3A inhibitor than ritonavir without enzyme-inducing properties. This review describes the differing effects of cobicistat and ritonavir on metabolic enzymes, which explains their differing drug-drug interactions, and summarizes some of the studied drug-drug interactions for cobicistat. It also outlines the clinical development and data for a once-daily darunavir/cobicistat FDC. This FDC thus allows for a once-daily treatment regimen (including background antiretrovirals) with reduced pill burden.
目前艾滋病病毒管理的一个重点是通过采用方便的剂型(包括固定剂量复方制剂,FDC)来减少服药负担,从而提高依从性。对于没有与达芦那韦耐药相关突变的艾滋病患者,指南推荐将HIV蛋白酶抑制剂达芦那韦与低剂量利托那韦(每日一次,800/100毫克)联合使用,并与其他抗逆转录病毒药物联合。对于在其他抗逆转录病毒药物中提高达芦那韦的血浆药物水平,考比司他是利托那韦的替代药物。考比司他是一种比利托那韦更具特异性的细胞色素P450 3A抑制剂,且没有酶诱导特性。本综述描述了考比司他和利托那韦对代谢酶的不同影响,这解释了它们不同的药物相互作用,并总结了一些针对考比司他研究过的药物相互作用。它还概述了每日一次的达芦那韦/考比司他FDC的临床开发和数据。这种FDC因此允许采用每日一次的治疗方案(包括背景抗逆转录病毒药物),同时减少了服药负担。