PDF(Pubmed)
Abstract：
Dolutegravir resistance is emerging in routine clinical contexts in southern Africa, primarily in patients with prior treatment experience failing dolutegravir-based antiretroviral therapy (ART). This potential issue was raised by The Nucleosides and Darunavir/Dolutegravir in Africa trial that compared dolutegravir and boosted protease inhibitor-based therapy as second-line ART, in which new dolutegravir resistance was observed at failure. However, recent data suggest that also at risk are patients who were transitioned to dolutegravir from non-nucleoside reverse transcriptase inhibitor-based ART while viremic. Identifying patients experiencing failure of dolutegravir with resistance will be difficult given current gaps in viral load monitoring and limited capacity for genotypic resistance testing. As a result, in the short term, most patients affected will go unrecognized, with particularly important implications for patients affected who have advanced HIV or who are pregnant/breastfeeding. Prospective research is needed to understand the scope of the problem, identify additional risk factors, and determine best management. In the short term, for most patients with dolutegravir resistance and prior non-nucleoside reverse transcriptase inhibitor exposure, the best option will be a timely switch to a regimen anchored by a boosted protease inhibitor, with a high genetic barrier to resistance.
摘要：
Dolutegravir耐药性在南部非洲的常规临床环境中出现，主要是先前治疗失败的基于dolutegravir的抗逆转录病毒治疗（ART）的患者。Nucleosids和Darunavir/Dolutegravir在非洲的试验提出了这个潜在的问题，该试验比较了基于dolutegravir和加强蛋白酶抑制剂的治疗作为二线ART，在失败时观察到新的dolutegravir耐药。然而,最近的数据表明,在病毒血症期间从基于非核苷逆转录酶抑制剂的ART过渡到dolutegravir的患者也处于危险之中.鉴于病毒载量监测的当前差距和基因型抗性测试的有限能力，确定患有耐药的dolutegravir失败的患者将是困难的。因此,在短期内,大多数受影响的患者将无法识别，对感染晚期艾滋病毒或怀孕/哺乳的患者具有特别重要的意义。需要前瞻性研究来了解问题的范围，确定额外的风险因素，并确定最佳管理。在短期内,对于大多数患有dolutegravir耐药和先前非核苷逆转录酶抑制剂暴露的患者，最好的选择是及时切换到以增强蛋白酶抑制剂为基础的治疗方案，具有很高的抗性遗传障碍。
