Parikh Urvi M, McCormick Kevin, van Zyl Gert, Mellors John W
aDivision of Infectious Diseases, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA bDivision of Medical Virology, Stellenbosch University and NHLS Tygerberg, Cape Town, South Africa.
Curr Opin HIV AIDS. 2017 Mar;12(2):182-189. doi: 10.1097/COH.0000000000000344.
Sensitive, scalable and affordable assays are critically needed for monitoring the success of interventions for preventing, treating and attempting to cure HIV infection. This review evaluates current and emerging technologies that are applicable for both surveillance of HIV drug resistance (HIVDR) and characterization of HIV reservoirs that persist despite antiretroviral therapy and are obstacles to curing HIV infection.
Next-generation sequencing (NGS) has the potential to be adapted into high-throughput, cost-efficient approaches for HIVDR surveillance and monitoring during continued scale-up of antiretroviral therapy and rollout of preexposure prophylaxis. Similarly, improvements in PCR and NGS are resulting in higher throughput single genome sequencing to detect intact proviruses and to characterize HIV integration sites and clonal expansions of infected cells.
Current population genotyping methods for resistance monitoring are high cost and low throughput. NGS, combined with simpler sample collection and storage matrices (e.g. dried blood spots), has considerable potential to broaden global surveillance and patient monitoring for HIVDR. Recent adaptions of NGS to identify integration sites of HIV in the human genome and to characterize the integrated HIV proviruses are likely to facilitate investigations of the impact of experimental 'curative' interventions on HIV reservoirs.
对于监测预防、治疗及尝试治愈HIV感染的干预措施的成效而言,迫切需要灵敏、可扩展且经济实惠的检测方法。本综述评估了当前及新兴技术,这些技术适用于HIV耐药性(HIVDR)监测以及HIV储存库的特征分析,尽管接受了抗逆转录病毒治疗,HIV储存库依然存在,并且是治愈HIV感染的障碍。
在抗逆转录病毒治疗持续扩大规模以及暴露前预防推广的过程中,下一代测序(NGS)有潜力被转化为用于HIVDR监测和监控的高通量、低成本方法。同样,PCR和NGS的改进使得更高通量的单基因组测序得以实现,以检测完整的前病毒,并对HIV整合位点和受感染细胞的克隆扩增进行特征分析。
当前用于耐药性监测的群体基因分型方法成本高且通量低。NGS与更简单的样本采集和存储基质(如干血斑)相结合,在扩大全球HIVDR监测和患者监控方面具有相当大的潜力。最近对NGS进行的调整,以识别HIV在人类基因组中的整合位点并对整合的HIV前病毒进行特征分析,可能会促进对实验性“治愈”干预措施对HIV储存库影响的研究。