Efficacy and Tolerability of 3 Nonnucleoside Reverse Transcriptase Inhibitor-Sparing Antiretroviral Regimens for Treatment-Naive Volunteers Infected With HIV-1
Efficacy and Tolerability of 3 Nonnucleoside Reverse Transcriptase Inhibitor-Sparing Antiretroviral Regimens for Treatment-Naive Volunteers Infected With HIV-1
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DOI：
10.7326/m14-1084
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发表时间：
2014-10-07
影响因子：
39.2
通讯作者：
Currier, Judith S.
中科院分区：
文献类型：
--
作者：
Lennox, Jeffrey L.;Landovitz, Raphael J.;Currier, Judith S.
背景资料：nonnucleotide reverse transcriptase transcriptase or-based antiretroviral therapy is not suitable for all treatment-naive HIV-infected personnel.Objective：To evaluate 3 nonnucleotide reverse transcriptase transcriptase or-sparing initial antiretroviral regimens to show equivalence for virologic efficacy and tolerability.Design：A phase 3，open-label study randomized in a 1：1：1 ratio with follow up for at least 96 wk.（临床试验政府网站：NCT 00811954）设置：美国和波多黎各的57个地点。患者：HIV-1 RNA水平大于1000拷贝/mL且对核苷类逆转录酶抑制剂或蛋白酶抑制剂无耐药性的18岁或以上未经治疗的人。干预：阿扎那韦，300 mg/d，利托那韦，100 mg/d;雷特格韦，400 mg，每日两次;或地瑞那韦，800 mg/d，利托那韦，100 mg/d，加上恩曲他滨，200 mg/d和富马酸替诺福韦酯，300 mg/d的组合。病毒学失败，定义为在16周或之后和24周之前确认的HIV-1 RNA水平大于1000拷贝/mL，或在24周或之后大于200拷贝/mL，和耐受性失败，定义为因毒性而停用阿扎那韦、雷特格韦或地瑞那韦。一个次要终点是病毒学疗效和耐受性相结合。结果：在1809名参与者中，所有成对比较的病毒学失败的发生率超过96周的等价范围内的等价定义为-10%至10%。雷特格韦和利托那韦加强的地瑞那韦的耐受性相当，而利托那韦加强的阿扎那韦导致耐受性中止的发生率分别比雷特格韦和利托那韦加强的地瑞那韦高12.7%和9.2%，主要是因为高胆红素血症。对于联合病毒学疗效和耐受性，利托那韦加强的达芦那韦上级利托那韦加强的阿扎那韦，雷特格韦上级两种蛋白酶抑制剂。抗逆转录病毒耐药的病毒学失败的时候是罕见的，但更频繁的raltegravir.Limitation：该试验是开放标签，利托那韦是不提供。结论：超过2年，所有3个方案达到病毒学控制的高和等效率。包含雷特格韦或利托那韦加强的地瑞那韦的方案的耐受性上级利托那韦加强的阿扎那韦方案。
Background: Nonnucleoside reverse transcriptase inhibitor-based antiretroviral therapy is not suitable for all treatment-naive HIV-infected persons.Objective: To evaluate 3 nonnucleoside reverse transcriptase inhibitor-sparing initial antiretroviral regimens to show equivalence for virologic efficacy and tolerability.Design: A phase 3, open-label study randomized in a 1: 1: 1 ratio with follow-up for at least 96 weeks. (ClinicalTrials.gov: NCT00811954)Setting: 57 sites in the United States and Puerto Rico.Patients: Treatment-naive persons aged 18 years or older with HIV-1 RNA levels greater than 1000 copies/mL without resistance to nucleoside reverse transcriptase inhibitors or protease inhibitors.Intervention: Atazanavir, 300 mg/d, with ritonavir, 100 mg/d; raltegravir, 400 mg twice daily; or darunavir, 800 mg/d, with ritonavir, 100 mg/d, plus combination emtricitabine, 200 mg/d, and tenofovir disoproxil fumarate, 300 mg/d.Measurements: Virologic failure, defined as a confirmed HIV-1 RNA level greater than 1000 copies/mL at or after 16 weeks and before 24 weeks or greater than 200 copies/mL at or after 24 weeks, and tolerability failure, defined as discontinuation of atazanavir, raltegravir, or darunavir for toxicity. A secondary end point was a combination of virologic efficacy and tolerability.Results: Among 1809 participants, all pairwise comparisons of incidence of virologic failure over 96 weeks showed equivalence within a margin of equivalence defined as -10% to 10%. Raltegravir and ritonavir-boosted darunavir were equivalent for tolerability, whereas ritonavir-boosted atazanavir resulted in a 12.7% and 9.2% higher incidence of tolerability discontinuation than raltegravir and ritonavir-boosted darunavir, respectively, primarily because of hyperbilirubinemia. For combined virologic efficacy and tolerability, ritonavir-boosted darunavir was superior to ritonavir-boosted atazanavir, and raltegravir was superior to both protease inhibitors. Antiretroviral resistance at the time of virologic failure was rare but more frequent with raltegravir.Limitation: The trial was open-label, and ritonavir was not provided.Conclusion: Over 2 years, all 3 regimens attained high and equivalent rates of virologic control. Tolerability of regimens containing raltegravir or ritonavir-boosted darunavir was superior to that of the ritonavir-boosted atazanavir regimen.