British Columbia Centre for Excellence in HIV/AIDS.
Department of Medicine, University of British Columbia, St Paul's Hospital, Vancouver.
Clin Infect Dis. 2017 Sep 1;65(5):796-802. doi: 10.1093/cid/cix428.
Transmitted drug resistance (TDR) may compromise response to antiretroviral therapy (ART). However, there are limited data on TDR patterns and impacts among people who use illicit drugs (PWUD).
Data were drawn from 2 prospective cohorts of PWUD in Vancouver, Canada. We characterized patterns of TDR among human immunodeficiency virus (HIV)-infected PWUD, and assessed its impacts on first-line ART virological outcomes.
Between 1996 and 2015, among 573 ART-naive PWUD (18% with recent HIV infection), the overall TDR prevalence was 9.8% (95% confidence interval [CI], 7.3%-12.2%), with an increasing trend over time, from 8.5% in 1996-1999 to 21.1% in 2010-2015 (P = .003), mainly driven by resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs). TDR-associated mutations were more common for NNRTIs (5.4%), followed by nucleoside reverse transcriptase inhibitors (3.0%) and protease inhibitors (1.9%). TDR prevalence was lower among recently infected PWUD (adjusted odds ratio, 0.39 [95% CI, .15-.87]). Participants with TDR had higher risk of virological failure than those without TDR (log-rank P = .037) in the first year of ART.
Between 1996 and 2015, TDR prevalence increased significantly among PWUD in Vancouver. Higher risk of virological failure among PWUD with TDR may be explained by some inappropriate ART prescribing, as well as undetected minority resistant variants in participants with chronic HIV infection. Our findings support baseline resistance testing early in the course of HIV infection to guide ART selection among PWUD in our setting.
传播性耐药(TDR)可能会影响抗逆转录病毒治疗(ART)的疗效。然而,目前有关吸毒者(PWUD)中 TDR 模式和影响的数据有限。
数据来自加拿大温哥华的两个前瞻性吸毒者队列。我们描述了 HIV 感染的吸毒者中 TDR 的模式,并评估了其对一线 ART 病毒学结果的影响。
在 1996 年至 2015 年间,573 名接受初次 ART 的吸毒者(18%为近期 HIV 感染者)中,总的 TDR 流行率为 9.8%(95%置信区间[CI],7.3%-12.2%),呈逐渐上升趋势,从 1996-1999 年的 8.5%上升到 2010-2015 年的 21.1%(P=0.003),主要是由于非核苷类逆转录酶抑制剂(NNRTI)耐药。与 NNRTI 相关的耐药突变更为常见(5.4%),其次是核苷类逆转录酶抑制剂(3.0%)和蛋白酶抑制剂(1.9%)。新近感染的吸毒者 TDR 发生率较低(调整后的比值比,0.39[95%CI,0.15-0.87])。在 ART 的第一年,TDR 组的病毒学失败风险高于无 TDR 组(对数秩检验 P=0.037)。
在 1996 年至 2015 年期间,温哥华的吸毒者中 TDR 流行率显著增加。TDR 组吸毒者病毒学失败的风险较高,可能是由于一些不合适的 ART 处方,以及慢性 HIV 感染者中未检测到少数耐药变异。我们的研究结果支持在 HIV 感染早期进行基线耐药性检测,以指导我们环境中吸毒者的 ART 选择。