Experimental Medicine, Faculty of Medicine, University of British Columbia, Vancouver, Canada; British Columbia Centre for Excellence in HIV/AIDS, Vancouver, Canada.
British Columbia Centre for Excellence in HIV/AIDS, Vancouver, Canada.
Clin Microbiol Infect. 2018 Feb;24(2):185-191. doi: 10.1016/j.cmi.2017.06.014. Epub 2017 Jun 23.
We aim to identify long-term trends in HIV drug resistance before and after combined antiretroviral therapy (cART) initiation.
IAS-USA (2015) mutations were identified in 23 271 HIV protease-reverse transcriptase sequences from 6543 treatment naïve adults in British Columbia. Participants who started cART between 1996 and 2014 were followed until April 2016. Equality of proportions test was used to compare the percentage of participants with acquired drug resistance (ADR) or transmitted drug resistance (TDR) in 1996, to those in 2014. Kaplan-Meier was used to estimate time to ADR in four drug resistance categories. Multivariable regression odds ratios (OR) of ADR for select clinical variables were determined by 5-year eras of cART initiation.
The proportion of individuals with ADR declined from 39% (51/132) to 3% (8/322) in 1996-2014 (p <0.0001), while the proportion with TDR increased from 12% (16/132) to 18% (59/322) (p 0.14). The estimated proportions of individuals with ADR rose to 29% (NNRTI), 28% (3TC/FTC), 14% (other nRTI), and 7% (PI) after >16 years of therapy. After 5 years on therapy, participants initiating cART in 1996-2000 had 5.5-times more 3TC/FTC ADR, 5.3-times more other nRTI ADR, 4.7-times more NNRTI ADR, and 24-times more PI ADR than those starting in 2011-2014. The individuals with highest odds of developing ADR in 1996-2010 were adherent to regimens at levels between 60% and 80%, which shifted to <40% adherent in 2011-2014.
HIV drug resistance transitioned from being primarily selected de-novo to being driven by TDR. Among those who started treatment in the past 5 years, ADR is rare and observed mostly in the lowest adherence strata.
我们旨在确定在开始联合抗逆转录病毒治疗（cART）前后 HIV 耐药性的长期趋势。
我们在不列颠哥伦比亚省的 6543 名未经治疗的成年参与者中鉴定了 IAS-USA（2015）突变。1996 年至 2014 年间开始接受 cART 的参与者随访至 2016 年 4 月。采用比例均等检验比较 1996 年和 2014 年获得性耐药（ADR）或传播性耐药（TDR）参与者的百分比。采用 Kaplan-Meier 法估计 4 种耐药类别中 ADR 的时间。通过 cART 起始的 5 年时代，确定选择临床变量的 ADR 多变量回归比值比（OR）。
1996-2014 年，ADR 个体的比例从 39%（51/132）降至 3%（8/322）（p<0.0001），而 TDR 个体的比例从 12%（16/132）增至 18%（59/322）（p=0.14）。经过>16 年的治疗，估计 ADR 个体的比例分别上升至 29%（NNRTI）、28%（3TC/FTC）、14%（其他 nRTI）和 7%（PI）。接受 cART 治疗 5 年后，1996-2000 年开始治疗的参与者发生 3TC/FTC ADR 的几率高 5.5 倍，发生其他 nRTI ADR 的几率高 5.3 倍，发生 NNRTI ADR 的几率高 4.7 倍，发生 PI ADR 的几率高 24 倍，而 2011-2014 年开始治疗的参与者发生这些 ADR 的几率低。1996-2010 年发展为 ADR 的个体的可能性最高，其治疗方案的依从性处于 60%至 80%之间，而 2011-2014 年则降至<40%。
HIV 耐药性从主要新出现的耐药性转变为 TDR 驱动的耐药性。在过去 5 年开始治疗的人群中，ADR 很少见，主要发生在最低依从性亚组中。
