Dolutegravir, the Second-Generation of Integrase Strand Transfer Inhibitors (INSTIs) for the Treatment of HIV

被引：63

作者：

Dow D.E. ^{[1
,2
,3
]}

Bartlett J.A. ^{[2
,4
,5
]}

机构：

[1] Duke University, DUMC 3499, Durham, 27710, NC

[2] Kilimanjaro Christian Medical Centre, Moshi

[3] Division of Infectious Diseases, Department of Pediatrics, Duke University Medical Center, Durham, NC

[4] Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, NC

[5] Duke Global Health Institute, Duke University, Durham, NC

来源：

Infectious Diseases and Therapy | 2014年 / 3卷 / 2期

基金：

美国国家卫生研究院;

关键词：

Antiretroviral therapy (ART); Dolutegravir (DTG); GSK1265744LA; HIV; Integrase strand transfer inhibitor (INSTI); Nanoparticle formulation;

D O I：

10.1007/s40121-014-0029-7

中图分类号：

学科分类号：

摘要：

The integrase strand transfer inhibitors (INSTIs) are the newest antiretroviral class in the HIV treatment armamentarium. Dolutegravir (DTG) is the only second-generation INSTI with FDA approval (2013). It has potential advantages in comparison to first-generation INSTI’s, including unboosted daily dosing, limited cross resistance with raltegravir and elvitegravir, and a high barrier to resistance. Clinical trials have evaluated DTG as a 50-mg daily dose in both treatment-naïve and treatment-experienced, INSTI-naïve participants. In those treatment-naïve participants with baseline viral load <100,000 copies/mL, DTG combined with abacavir and lamivudine was non-inferior and superior to fixed-dose combination emtricitabine/tenofovir/efavirenz. DTG was also superior to the protease inhibitor regimen darunavir/ritonavir in treatment-naïve participants regardless of baseline viral load. Among treatment-experienced patients naïve to INSTI, DTG (50 mg daily) demonstrated both non-inferiority and superiority when compared to the first-generation INSTI raltegravir (400 mg twice daily) regardless of the background regimen. No phenotypically significant DTG resistance has been demonstrated in INSTI-naïve participant trials. The VIKING trials evaluated DTG’s ability to treat persons with HIV with prior INSTI exposure. VIKING demonstrated twice-daily DTG was more efficacious than daily dosing when treating participants receiving and failing first-generation INSTI regimens. DTG maintained potency against single mutations from any of the three major INSTI pathways (Y143, H155, Q148); however, the Q148 mutation with two or more additional mutations significantly reduced its potency. The long-acting formulation of DTG, GSK1265744LA, is the next innovation in this second-generation INSTI class, holding promise for the future of HIV prevention and treatment. © 2014, The Author(s).

引用

页码：83 / 102

页数：19

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