Kamelian Kimia, Lepik Katherine J, Chau William, Yip Benita, Zhang Wendy W, Lima Viviane Dias, Robbins Marjorie A, Woods Conan, Olmstead Andrea, Joy Jeffrey B, Barrios Rolando, Harrigan P Richard
BC Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada.
University of British Columbia, Department of Medicine, Division of AIDS, Vancouver, Canada.
Open Forum Infect Dis. 2019 Feb 12;6(3):ofz060. doi: 10.1093/ofid/ofz060. eCollection 2019 Mar.
Integrase strand transfer inhibitors (INSTIs) are highly efficacious and well tolerated antiretrovirals with fewer adverse side-effects relative to other classes of antiretrovirals. The use of INSTIs raltegravir, elvitegravir, and dolutegravir has increased dramatically over recent years. However, there is limited information about the evolution and prevalence of INSTI resistance mutations in clinical human immunodeficiency virus populations.
Human immunodeficiency virus-1-positive individuals ≥19 years were included if they received ≥1 dispensed prescription of antiretroviral therapy (ART) in British Columbia between 2009 and 2016 (N = 9358). Physician-ordered drug resistance tests were analyzed and protease inhibitor (PI), reverse-transcriptase inhibitor (RT), and INSTI resistance were defined as having ≥1 sample with a combined, cumulative score ≥30 by Stanford HIV Drug Resistance Algorithm version 7.0.1.
Although most ART-treated individuals were tested for PI and RT resistance, INSTI resistance testing lagged behind the uptake of INSTIs among INSTI-treated individuals (11% in 2009; 34% in 2016). The prevalence of INSTI resistance was relatively low, but it increased from 1 to 7 per 1000 ART-treated individuals between 2009 and 2016 ( < .0001, R = 0.98). Integrase strand transfer inhibitor resistance mutations increased at integrase codons 66, 97, 140, 148, 155, and 263.
The prevalence of INSTI resistance remains low compared with PI and RT resistance in ART-treated populations but is expanding with increased INSTI use.
整合酶链转移抑制剂（INSTIs）是高效且耐受性良好的抗逆转录病毒药物，与其他类别的抗逆转录病毒药物相比，副作用较少。近年来，雷特格韦、埃替格韦和多替拉韦等整合酶链转移抑制剂的使用显著增加。然而，关于临床人类免疫缺陷病毒群体中整合酶链转移抑制剂耐药突变的演变和流行情况的信息有限。
纳入年龄≥19岁的人类免疫缺陷病毒1型阳性个体，这些个体在2009年至2016年期间在不列颠哥伦比亚省接受了≥1次抗逆转录病毒治疗（ART）配药处方（N = 9358）。对医生要求的耐药性检测进行分析，蛋白酶抑制剂（PI）、逆转录酶抑制剂（RT）和整合酶链转移抑制剂耐药性定义为根据斯坦福HIV耐药性算法7.0.1，≥1个样本的综合累积评分≥30。
尽管大多数接受抗逆转录病毒治疗的个体接受了蛋白酶抑制剂和逆转录酶抑制剂耐药性检测，但整合酶链转移抑制剂耐药性检测在接受整合酶链转移抑制剂治疗的个体中落后于整合酶链转移抑制剂的使用（2009年为11%；2016年为34%）。整合酶链转移抑制剂耐药性的流行率相对较低，但在2009年至2016年期间，每1000名接受抗逆转录病毒治疗的个体中从1例增加到7例（P <.0001，R = 0.98）。整合酶链转移抑制剂耐药突变在整合酶密码子66、97、140、148、155和263处增加。
在接受抗逆转录病毒治疗的人群中，与蛋白酶抑制剂和逆转录酶抑制剂耐药性相比，整合酶链转移抑制剂耐药性的流行率仍然较低，但随着整合酶链转移抑制剂使用的增加而扩大。
