Adis, 41 Centorian Drive, Private Bag 65901 Mairangi Bay, North Shore, 0754, Auckland, New Zealand,
Drugs. 2014 Jan;74(1):99-125. doi: 10.1007/s40265-013-0159-3.
The latest HIV-1 protease inhibitor (PI) darunavir (Prezista™) has a high genetic barrier to resistance development and is active against wild-type HIV and HIV strains no longer susceptible to some older PIs. Ritonavir-boosted darunavir, as a component of antiretroviral therapy (ART), is indicated for the treatment of HIV-1 infection in adult and paediatric patients (aged ≥3 years), with or without treatment experience (details vary depending on region of approval). Several open-label or partially-blinded trials have evaluated the efficacy of ritonavir-boosted darunavir ART regimens for up to 192 weeks in these settings. In treatment-naïve adults, once-daily boosted darunavir was no less effective in establishing virological suppression than once- or twice-daily boosted lopinavir, yet was more effective at maintaining suppression long term. Moreover, treatment-experienced adults with no darunavir resistance-associated mutations (RAMs) had no less effective viral load suppression with once-daily than with twice-daily boosted darunavir. In treatment-experienced adults, including some with multiple major PI RAMs, twice-daily boosted darunavir was more effective than twice-daily boosted lopinavir or boosted control PIs in reducing viral load, and provided virological benefit as part of a salvage regimen in those with few remaining treatment options. Boosted darunavir also reduced viral load when administered once-daily in treatment-naïve adolescents or twice-daily in treatment-experienced children and adolescents. Boosted darunavir is generally well tolerated, with gastrointestinal disturbances and lipid abnormalities among the most common tolerability issues. It has a lipid profile more favourable than that of boosted lopinavir in terms of total cholesterol and triglyceride changes and, when administered once daily, its lipid effects are generally similar to those of boosted atazanavir. Thus, boosted darunavir is a useful option for the ART regimens of adult and paediatric patients with HIV-1 infection.
最新的 HIV-1 蛋白酶抑制剂（PI）达芦那韦（PrezistaTM）具有较高的耐药基因屏障，对野生型 HIV 以及对一些较老的 PI 不再敏感的 HIV 株均具有活性。利托那韦增强的达芦那韦，作为抗逆转录病毒疗法（ART）的一部分，适用于治疗成人和儿科患者（年龄≥3 岁）的 HIV-1 感染，无论是否有治疗经验（具体情况因批准地区而异）。多项开放标签或部分盲法试验评估了这些情况下利托那韦增强的达芦那韦 ART 方案长达 192 周的疗效。在初治成人中，每日一次的增强型达芦那韦在建立病毒学抑制方面与每日一次或两次的增强型洛匹那韦同样有效，但在长期维持抑制方面更有效。此外，无达芦那韦耐药相关突变（RAM）的治疗经验成人每日一次的病毒载量抑制与每日两次的增强型达芦那韦同样有效。在治疗经验成人中，包括一些具有多种主要 PI RAM 的患者，每日两次的增强型达芦那韦比每日两次的增强型洛匹那韦或增强型对照 PI 更有效地降低病毒载量，并且在治疗选择有限的患者中作为挽救治疗方案的一部分提供病毒学益处。在初治青少年中每日一次给予增强型达芦那韦或在治疗经验青少年中每日两次给予增强型达芦那韦也可降低病毒载量。增强型达芦那韦一般耐受性良好，最常见的耐受性问题是胃肠道紊乱和脂类异常。与增强型洛匹那韦相比，增强型达芦那韦的总胆固醇和甘油三酯变化的血脂谱更有利，当每日一次给药时，其血脂效应通常与增强型阿扎那韦相似。因此，增强型达芦那韦是治疗 HIV-1 感染的成人和儿科患者的 ART 方案的一个有用选择。
