Infectious Diseases Service, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain.
Sorbonne University, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136).
Curr Opin Infect Dis. 2018 Jun;31(3):237-245. doi: 10.1097/QCO.0000000000000453.
Dolutegravir (DTG) is a second-generation integrase strand transfer inhibitor (InSTI) with an outstanding antiviral potency, good tolerability, good pharmacokinetic profile with a lack of major drug-drug interactions, and a barrier to resistance higher than the other compounds of the class (raltegravir and elvitegravir) and allegedly as high as that of boosted protease inhibitors. For these reasons, DTG, after successful results in a context of triple therapy in various clinical scenarios, has been investigated mostly by independent investigators in less-drug regimens, including dolutegravir monotherapy, in the context of a growing clinical interest for adjusting successful antiretroviral therapy to the increasing number of limitations for standard antiretroviral therapy in some HIV-infected patients. However, the development of genotypic resistance in case of failure to DTG monotherapy was unexpected.
Data on efficacy and resistance from preclinical studies, randomized clinical trials and clinical cohorts of HIV-infected patients treated with DTG monotherapy published in indexed journals or presented at international meetings were reviewed.
Monotherapy with dolutegravir has a high rate for resistance selection in the integrase gene through different pathways in case of virological failure.
多替拉韦（DTG）是第二代整合酶链转移抑制剂（INSTI），具有出色的抗病毒效力、良好的耐受性、良好的药代动力学特性，且无主要药物相互作用，耐药屏障高于同类药物（拉替拉韦和艾维雷韦），据称与增效蛋白酶抑制剂相当。由于这些原因，DTG 在各种临床情况下的三联疗法中取得成功后，主要由独立研究者在较少药物方案中进行了研究，包括多替拉韦单药治疗，这是因为在越来越多的 HIV 感染者中，标准抗逆转录病毒疗法的局限性增加，对成功的抗逆转录病毒疗法进行调整的临床需求不断增长。然而，在 DTG 单药治疗失败的情况下，出现了基因型耐药的情况，这是出乎意料的。
对已发表于索引期刊或在国际会议上的、来自于针对 HIV 感染者进行 DTG 单药治疗的临床前研究、随机临床试验和临床队列研究的疗效和耐药性数据进行了综述。
在病毒学失败的情况下，整合酶基因中通过不同途径发生耐药性选择，导致多替拉韦单药治疗的耐药率很高。
