Wertheim Joel O, Oster Alexandra M, Johnson Jeffrey A, Switzer William M, Saduvala Neeraja, Hernandez Angela L, Hall H Irene, Heneine Walid
Department of Medicine, University of California, San Diego, CA, 92093, USA.
ICF International, Atlanta, GA, 30329, USA.
Virus Evol. 2017 Apr 19;3(1):vex008. doi: 10.1093/ve/vex008. eCollection 2017 Jan.
Test-and-treat programs are central to the global control of HIV, but transmitted drug resistance threatens the effectiveness of these programs. HIV mutations conferring resistance to antiretroviral drugs reduce replicative fitness , but their effect on propagation is less understood. Here, we estimate transmission fitness of these mutations in antiretroviral-naïve populations in the U.S. National HIV Surveillance System by comparing their frequency of clustering in a genetic transmission network relative with wild-type viruses. The large dataset (66,221 persons), comprising 30,196 antiretroviral-naïve persons, permitted the evaluation of sixty-nine resistance mutations. Decreased transmission fitness was demonstrated for twenty-three mutations, including M184V. In contrast, many high prevalence mutations (e.g. K103N, Y181C, and L90M) had transmission fitness that was indistinguishable from or exceeded wild-type fitness, permitting the establishment of large, self-sustaining drug resistance reservoirs. We highlight implications of these findings on strategies to preserve global treatment effectiveness.
检测与治疗项目是全球控制艾滋病病毒（HIV）的核心，但传播性耐药性威胁着这些项目的有效性。赋予对抗逆转录病毒药物耐药性的HIV突变会降低复制适应性，但其对传播的影响却鲜为人知。在此，我们通过比较在美国国家HIV监测系统中未接受过抗逆转录病毒治疗人群的基因传播网络中，这些突变与野生型病毒的聚集频率，来估计这些突变的传播适应性。这个包含66221人、其中30196人为未接受过抗逆转录病毒治疗者的大型数据集，使得对69种耐药突变进行评估成为可能。23种突变，包括M184V，显示出传播适应性降低。相比之下，许多高流行率的突变（如K103N、Y181C和L90M）的传播适应性与野生型相当或超过野生型，这使得能够建立大型的、自我维持的耐药库。我们强调了这些发现对保持全球治疗效果策略的影响。
