McCluskey Suzanne M, Gandhi Monica
Medical Practice Evaluation Center and Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Division of HIV, Infectious Diseases and Global Medicine, University of California San Francisco, San Francisco, CA, USA.
Lancet HIV. 2025 Jun 19. doi: 10.1016/S2352-3018(25)00127-4.
Integrase strand transfer inhibitor (INSTI)-based regimens became a first-line treatment for HIV worldwide in 2018, with 93% of people with HIV who are on antiretroviral therapy (ART) estimated to be taking dolutegravir-based regimens as of 2023. Since the genetic barrier to resistance of dolutegravir is not impenetrable, rising rates of dolutegravir resistance among those with virological failure on this drug regimen have been reported. Risk factors for dolutegravir resistance include treatment experience, having background resistance to the nucleoside reverse transcriptase inhibitors in the regimen, switching to tenofovir, lamivudine, and dolutegravir when viraemic on a former regimen, previous experience with first-generation INSTIs, and being on dolutegravir monotherapy or dual therapy, with rates higher in children than in adults. HIV drug resistance does not emerge if selective drug pressure is not present, so some exposure to the ART regimen with virological failure is associated with higher rates of resistance than complete non-adherence. Detectable objective metrics of adherence (eg, ART drug concentrations in urine, plasma, dried blood spots, and hair) have been associated with high levels of viral resistance and can be used to triage who needs resistance testing the most.
基于整合酶链转移抑制剂（INSTI）的治疗方案在2018年成为全球范围内HIV的一线治疗方案，截至2023年，估计93%接受抗逆转录病毒治疗（ART）的HIV感染者正在使用基于多替拉韦的治疗方案。由于多替拉韦的耐药基因屏障并非不可逾越，已有报道称在该药物治疗方案中出现病毒学失败的患者中，多替拉韦耐药率不断上升。多替拉韦耐药的危险因素包括治疗经历、对治疗方案中的核苷类逆转录酶抑制剂有背景耐药、在前一治疗方案病毒血症时换用替诺福韦、拉米夫定和多替拉韦、既往使用第一代整合酶链转移抑制剂的经历以及接受多替拉韦单药治疗或双药治疗，儿童的耐药率高于成人。如果不存在选择性药物压力，HIV耐药就不会出现，因此与完全不依从相比，在病毒学失败的ART治疗方案中有一定暴露与更高的耐药率相关。可检测的依从性客观指标（如尿液、血浆、干血斑和头发中的ART药物浓度）与高水平的病毒耐药相关，可用于对最需要进行耐药检测的人群进行分类。
