Rhee Soo-Yon, Clutter Dana, Hare C Bradley, Tchakoute Christophe T, Sainani Kristin, Fessel W Jeffrey, Hurley Leo, Slome Sally, Pinsky Benjamin A, Silverberg Michael J, Shafer Robert W
Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, California, USA.
Department of Infectious Diseases, Kaiser Permanente Northern California, South San Francisco, California, USA.
Open Forum Infect Dis. 2020 Aug 6;7(9):ofaa316. doi: 10.1093/ofid/ofaa316. eCollection 2020 Sep.
There are few descriptions of virologic failure (VF) and acquired drug resistance (HIVDR) in large cohorts initiating contemporary antiretroviral therapy (ART).
We studied all persons with HIV (PWH) in a California clinic population initiating ART between 2010 and 2017. VF was defined as not attaining virologic suppression, discontinuing ART, or virologic rebound prompting change in ART.
During the study, 2315 PWH began ART. Six companion drugs were used in 93.3% of regimens: efavirenz, elvitegravir/c, dolutegravir, b-darunavir, rilpivirine, and raltegravir. During a median follow-up of 36 months, 214 (9.2%) PWH experienced VF (2.8 per 100 person-years) and 62 (2.7%) experienced HIVDR (0.8 per 100 person-years). In multivariable analyses, younger age, lower CD4 count, higher virus load, and b-atazanavir were associated with increased VF risk; lower CD4 count, higher virus load, and nevirapine were associated with increased HIVDR risk. Compared with efavirenz, dolutegravir, raltegravir, and b-darunavir were associated with reduced HIVDR risk. Risks of VF and HIVDR were not significantly associated with ART initiation year. Of the 62 PWH with HIVDR, 42 received an non-nucleoside RT inhibitor (NNRTI), 15 an integrase-strand transfer inhibitor (INSTI), and 5 a protease inhibitor (PI). Among those with HIVDR on an NNRTI or first-generation INSTI, 59% acquired dual class resistance and 29% developed tenofovir resistance; those receiving a PI or dolutegravir developed just M184V.
Despite the frequent use of contemporary ART regimens, VF and HIVDR continue to occur. Further efforts are required to improve long-term ART virological responses to prevent the consequences of ongoing HIV-1 replication including virus transmission and HIVDR.
在开始当代抗逆转录病毒疗法（ART）的大型队列中，关于病毒学失败（VF）和获得性耐药（HIVDR）的描述很少。
我们研究了2010年至2017年间在加利福尼亚一家诊所开始接受ART治疗的所有艾滋病毒感染者（PWH）。VF定义为未实现病毒学抑制、停止ART治疗或病毒学反弹促使ART治疗方案改变。
在研究期间，2315名PWH开始接受ART治疗。93.3%的治疗方案使用了六种辅助药物：依非韦伦、埃替拉韦/考比司他、多替拉韦、b - 达芦那韦、利匹韦林和拉替拉韦。在中位随访36个月期间，214名（9.2%）PWH经历了VF（每100人年2.8例），62名（2.7%）经历了HIVDR（每100人年0.8例）。在多变量分析中，年龄较小、CD4细胞计数较低、病毒载量较高以及使用b - 阿扎那韦与VF风险增加相关；CD4细胞计数较低、病毒载量较高以及使用奈韦拉平与HIVDR风险增加相关。与依非韦伦相比，多替拉韦、拉替拉韦和b - 达芦那韦与HIVDR风险降低相关。VF和HIVDR的风险与ART开始年份无显著关联。在62名患有HIVDR的PWH中，42名接受了非核苷类逆转录酶抑制剂（NNRTI），15名接受了整合酶链转移抑制剂（INSTI），5名接受了蛋白酶抑制剂（PI）。在接受NNRTI或第一代INSTI治疗且出现HIVDR的患者中，59%获得了双重耐药，29%出现了替诺福韦耐药；接受PI或多替拉韦治疗的患者仅出现M184V突变。
尽管当代ART方案使用频繁，但VF和HIVDR仍会发生。需要进一步努力改善长期ART的病毒学反应，以预防持续的HIV - 1复制所带来的后果，包括病毒传播和HIVDR。
