Dolutegravir
Dolutegravir
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多替拉韦
作者：
Candice J. Mercadel;Jessica W. Skelley;J. A. Kyle;L. Elmore
目的：综述dolutegravir（Tivicay）（第三类整合酶链转移抑制剂（TIMI））治疗成人人类免疫缺陷病毒（HIV-1）的疗效、安全性、药代动力学、药效学、给药方式、药物相互作用和成本。数据来源：MEDLINE、International Pharmaceutical Abstracts、ClinicalTrials.gov和Google Scholar检索（2000年1月至2014年5月）以英文发表且仅限于人类受试者的文章，使用关键词抗逆转录病毒药物、HIV整合酶链转移抑制剂、度鲁特韦、DTG和S/GSK 1349572。研究选择和数据提取：在MEDLINE、国际药学文摘、ClinicalTrials.gov和Google Scholar检索后，确定了6项临床试验并纳入本综述。选择并评价了评价度鲁特韦在人体中的安全性和有效性的III/IV期研究。数据合成：在治疗初治和有经验的患者中，当加用背景治疗时，度鲁特韦在抑制病毒载量方面不劣于雷特格韦。阿巴卡韦/拉米夫定/度鲁特韦在抑制病毒载量方面不劣于依法韦仑/恩曲他滨/富马酸替诺福韦酯和地瑞那韦/利托那韦加背景治疗。在基线时具有多类抗逆转录病毒耐药的患者中，dolutegravir在第8天将HIV RNA降低了1.4 log 10拷贝/mL，63%的患者在第8周达到了病毒学抑制，并且在随访的第48周或第96周，治疗经历过INSTI耐药的患者中保持了效力。结论：多鲁特韦是一种安全，有效和耐受性良好的治疗方案，适用于成人HIV-1，即使在对其他抗逆转录病毒药物耐药的情况下。
Objective: To review the efficacy, safety, pharmacokinetics, pharmacodynamics, administration, drug interactions, and cost of dolutegravir (Tivicay), a third in class integrase strand transfer inhibitor (INSTI), for the treatment of human immunodeficiency virus (HIV-1) in adults. Data Sources: MEDLINE, International Pharmaceutical Abstracts, ClinicalTrials.gov, and Google Scholar searches (January 2000 to May 2014) were conducted for articles published in English and limited to human subjects, using the key words antiretroviral drugs, HIV integrase strand transfer inhibitors, dolutegravir, DTG, and S/GSK1349572. Study Selection and Data Extraction: Following MEDLINE, International Pharmaceutical Abstracts, ClinicalTrials.gov, and Google Scholar searches, 6 clinical trials were identified and included in this review. Phase III/IV studies evaluating the safety and efficacy of dolutegravir in humans were selected and evaluated. Data Synthesis: In treatment naïve and experienced patients dolutegravir was noninferior to raltegravir at suppressing viral load when added to background therapy. Abacavir/lamivudine/dolutegravir was noninferior to efavirenz/emtricitabine/tenofovir disoproxil fumarate and darunavir/ritonavir plus background therapy at suppressing viral load. In patients with multiple-class antiretroviral resistance at baseline, dolutegravir decreased HIV RNA by 1.4 log10 copies/mL at day 8, 63% of patients had achieved virologic suppression at week 8, and retained potency in treatment-experienced INSTI-resistant patients up to week 48 or 96 of follow-up. Conclusion: Dolutegravir is a safe, effective, and well-tolerated treatment option for adults with HIV-1, even in the setting of resistance to other antiretrovirals.