Soria Jaime, Mugruza Raquel, Levine Molly, León Segundo R, Arévalo Jorge, Ticona Eduardo, Beck Ingrid A, Frenkel Lisa M
1 Infectious and Tropical Diseases Department. Hospital Nacional Dos de Mayo, Lima, Peru.
2 Northern Pacific Global Health Research Fellows Training Consortium, University of Washington, Seattle, Washington.
AIDS Res Hum Retroviruses. 2019 Feb;35(2):150-154. doi: 10.1089/AID.2018.0239. Epub 2019 Jan 22.
Access to nucleoside reverse transcriptase inhibitor (NRTI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) first-line antiretroviral therapy (ART) for HIV has been increasing in Peru since a national ART program was initiated in 2004. Between 2007 and 2009, we found a 1% prevalence of pre-ART HIV drug resistance (PDR) among antiretroviral (ARV)-naive Peruvians. Given that PDR has been associated with virologic failure (VF) of ART, in 2014-2015 we enrolled a follow-up cohort at the same institution to determine whether the rate of transmitted resistance had increased and compared virologic outcomes of those with and without PDR. Blood specimens from ARV-naive individuals were assessed for PDR to NNRTI-based ART by an oligonucleotide ligation assay (OLA) sensitive to 2% mutant within an individual's HIV quasispecies at reverse transcriptase codons M41L, K65R, K103N, Y181C, M184V, and G190A, and by Sanger consensus sequencing (CS). Rates of VF (plasma HIV RNA >200 copies/mL) were compared between those with and without PDR. Among 122 ARV-naive adults, PDR was detected by OLA in 17 (13.9%) adults. Compared with the 2007-2009 cohort, the proportion with PDR at OLA codons was significantly increased (p < .001). A total of 11 of 19 OLA mutations conferring high-level drug resistance were also detected by CS, and 8 additional participants had mutations encoding low-level resistance detected by CS for a total of 25 participants (20.5%). VF at month 6 of NNRTI-ART appeared greater in participants with versus without PDR [4/18 (22.2%) vs. 3/71 (4.2%); p = .03]. An increasing prevalence of PDR was detected among ARV-naive Peruvians. Studies are needed to determine risks of specific PDR mutations.
自2004年启动全国抗逆转录病毒治疗（ART）项目以来，秘鲁获得核苷类逆转录酶抑制剂（NRTI）和非核苷类逆转录酶抑制剂（NNRTI）一线抗HIV病毒治疗的机会一直在增加。在2007年至2009年期间，我们发现初治的秘鲁人中ART前HIV耐药（PDR）患病率为1%。鉴于PDR与ART的病毒学失败（VF）相关，在2014年至2015年，我们在同一机构纳入了一个随访队列，以确定传播耐药率是否增加，并比较有无PDR者的病毒学结局。通过对逆转录酶密码子M41L、K65R、K103N、Y181C、M184V和G190A处个体HIV准种内2%突变敏感的寡核苷酸连接分析（OLA）以及桑格一致性测序（CS），对初治个体的血标本进行基于NNRTI的ART的PDR评估。比较有无PDR者的VF率（血浆HIV RNA>200拷贝/mL）。在122名初治成人中，17名（13.9%）成人通过OLA检测到PDR。与2007 - 2009年队列相比，OLA密码子处有PDR的比例显著增加（p<0.001）。通过CS还检测到19个赋予高水平耐药性的OLA突变中的11个，另外8名参与者通过CS检测到编码低水平耐药性的突变，共有25名参与者（20.5%）。接受NNRTI - ART治疗6个月时，有PDR的参与者的VF似乎高于无PDR者[4/18（22.2%）对3/71（4.2%）；p = 0.03]。在初治的秘鲁人中检测到PDR患病率在增加。需要开展研究以确定特定PDR突变的风险。
