Subgroup analyses of Maraviroc in previously treated R5 HIV-1 infection
Subgroup analyses of Maraviroc in previously treated R5 HIV-1 infection
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DOI：
10.1056/nejmoa0803154
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发表时间：
2008-10-02
影响因子：
158.5
通讯作者：
van der Ryst, Elna
中科院分区：
文献类型：
--
作者：
Faetkenheuer, Gerd;Nelson, Mark;van der Ryst, Elna
背景：我们对马拉韦罗与优化疗法在病毒血症抗逆转录病毒治疗经验患者中的综合结果进行了亚组分析（MOTIVATE）1和MOTIVATE 2研究，以更好地表征马拉韦罗在关键亚组患者中的疗效和安全性。CC趋化因子受体5（CCR 5）delta 32基因型、筛选时的病毒载量、优化背景治疗（OBT）中是否使用恩夫韦肽、基线CD 4细胞计数、同时给予的活性抗逆转录病毒药物数量、首次使用选定的背景药物和基线时的嗜性。评价治疗失败时病毒嗜性和CD 4计数的变化。同时感染B型肝炎病毒（HBV）或丙型肝炎病毒（HCV）的患者的转氨酶水平数据也进行了分析。结果马拉韦罗加OBT治疗获益超过安慰剂加OBT显示在所有亚组，包括基线时CD 4细胞计数低的患者，筛选时病毒载量高的患者，以及那些没有接受OBT活性药物的患者。根据首次使用选定的背景药物进行的病毒学应答分析显示，在马拉韦罗治疗开始时，在马拉韦罗基础上添加一种强效新药具有额外的获益。更多马拉韦罗治疗失败的患者在治疗失败时病毒与CXC趋化因子受体4（CXCR 4）结合，但与安慰剂治疗失败的患者相比，没有证据表明这些患者治疗失败时CD 4细胞计数减少。对合并感染HBV或HCV的患者进行的亚组分析显示，与基线相比，没有证据表明存在过度的肝毒性作用。结论对第48周汇总数据的亚组分析表明，马拉维罗为广泛的R5 HIV-1感染患者提供了一种有价值的治疗选择。之前接受过治疗。（临床试验。政府编号，NCT 00098306和NCT 00098722。
Background We conducted subanalyses of the combined results of the Maraviroc versus Optimized Therapy in Viremic Antiretroviral Treatment- Experienced Patients (MOTIVATE) 1 and MOTIVATE 2 studies to better characterize the efficacy and safety of maraviroc in key subgroups of patients.Methods We analyzed pooled data from week 48 from the two studies according to sex, race or ethnic group, clade, CC chemokine receptor 5 (CCR5) delta32 genotype, viral load at the time of screening, the use or nonuse of enfuvirtide in optimized background therapy (OBT), the baseline CD4 cell count, the number of active antiretroviral drugs coadministered, the first use of selected background agents, and tropism at baseline. Changes in viral tropism and the CD4 count at treatment failure were evaluated. Data on aminotransferase levels in patients coinfected with hepatitis B virus (HBV) or hepatitis C virus (HCV) were also analyzed.Results A treatment benefit of maraviroc plus OBT over placebo plus OBT was shown in all subgroups, including patients with a low CD4 cell count at baseline, those with a high viral load at screening, and those who had not received active agents in OBT. Analyses of the virologic response according to the first use of selected background drugs showed the additional benefit of adding a potent new drug to maraviroc at the initiation of maraviroc therapy. More patients in whom maraviroc failed had a virus binding to the CXC chemokine receptor 4 (CXCR4) at failure, but there was no evidence of a decrease in the CD4 cell count at failure in such patients as compared with those in whom placebo failed. Subanalyses involving patients coinfected with HBV or HCV revealed no evidence of excess hepatotoxic effects as compared with baseline.Conclusions Subanalyses of pooled data from week 48 indicate that maraviroc provides a valuable treatment option for a wide spectrum of patients with R5 HIV-1 infection who have been treated previously. (ClinicalTrials. gov numbers, NCT00098306 and NCT00098722.).