Antiretroviral Drug Resistance in HIV Sequences From People Who Inject Drugs and Men Who Have Sex With Men Across 21 Cities in India.
Antiretroviral Drug Resistance in HIV Sequences From People Who Inject Drugs and Men Who Have Sex With Men Across 21 Cities in India.
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DOI：
10.1093/ofid/ofac481
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发表时间：
2022-10
影响因子：
4.2
通讯作者：
中科院分区：
文献类型：
--
作者：
在印度公共部门的人类免疫缺陷病毒（HIV）治疗中，耐药性检测存在局限，针对普遍存在的耐药突变（DRMs）的系统性抽样很少，尤其是在男男性行为者（MSM）和注射吸毒者（PWID）群体中。
2016 - 2017年，我们对从印度21个城市招募的915名有病毒血症且自述有抗逆转录病毒治疗（ART）经历或无此经历的注射吸毒者及男男性行为者的HIV序列进行了基因型耐药检测。我们使用逻辑回归分析与耐药相关的因素，并通过系统发育分析评估传播性耐药的证据。
在进行测序的915名参与者中，年龄中位数为31岁，其中436名是男男性行为者，191名有抗逆转录病毒治疗经历。总体而言，有抗逆转录病毒治疗经历的参与者中有62.8%，无抗逆转录病毒治疗经历的参与者中有14.4%，对一种或多种药物存在低水平或更高水平的耐药。有抗逆转录病毒治疗经历的参与者中，富马酸替诺福韦二吡呋酯耐药率为25.7%，无抗逆转录病毒治疗经历的参与者中该耐药率为1.11%。核苷类逆转录酶抑制剂和非核苷类逆转录酶抑制剂的耐药比例最高，且男男性行为者参与者中的耐药情况显著多于注射吸毒者。系统发育分析显示，在有耐药且聚类的无抗逆转录病毒治疗经历的参与者中，54.6% 存在共同的耐药突变，这表明可能发生了传播性耐药。
一线治疗出现病毒学失败的患者盲目换用替诺福韦/拉米夫定/多替拉韦，由于对替诺福韦和拉米夫定耐药，实际上可能仅在接受多替拉韦单药治疗。虽然预计多替拉韦对印度大多数患者具有完全活性，但仍需后续跟踪，以了解耐药可能如何影响长期治疗效果。
Drug resistance testing is limited in public-sector human immunodeficiency virus (HIV) care in India, and there are few systematic samplings for prevalent drug resistance mutations (DRMs), particularly among men who have sex with men (MSM) and people who inject drugs (PWID). We conducted genotypic resistance testing on 915 HIV sequences sampled from viremic self-reported antiretroviral therapy (ART) experienced and naive PWID and MSM recruited from 21 cities across India in 2016–2017. We analyzed factors associated with resistance using logistic regression and evaluated evidence for transmitted resistance using phylogenetic analyses. Of the 915 participants sequenced, median age was 31, 436 were MSM, and 191 were ART experienced. Overall, 62.8% of ART-experienced participants and 14.4% of ART-naive participants were found to have low-level resistance or higher to 1 or more classes of drugs. Prevalence of tenofovir disoproxil fumarate resistance was 25.7% in ART-experienced participants and 1.11% in ART-naive participants. The highest proportion of drug resistance was seen across nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors, and resistance was significantly more common among MSM participants than PWID. Phylogenetic analyses revealed that 54.6% of ART-naive participants with resistance who clustered had shared DRMs, suggesting transmitted resistance may have occurred. Patients experiencing virologic failure on first-line therapy switched blindly to tenofovir/lamivudine/dolutegravir may effectively be receiving dolutegravir monotherapy due to resistance to tenofovir and lamivudine. While dolutegravir is expected to have full activity in the majority of patients in India, follow-up is needed to understand how resistance may affect long-term outcomes.
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