监测艾滋病毒耐药性和治疗的未来技术。

Urvi M Parikh, Kevin McCormick, Gert van Zyl, John W Mellors
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摘要

审查目的:迫切需要敏感、可扩展和负担得起的检测方法来监测预防、治疗和试图治愈艾滋病毒感染的干预措施的成功。这篇综述评估了目前和新兴的技术,这些技术既适用于监测艾滋病毒耐药性(HIVDR),也适用于表征尽管接受了抗逆转录病毒治疗但仍然存在的艾滋病毒库,这些技术是治愈艾滋病毒感染的障碍。最近的发现:下一代测序(NGS)有可能在抗逆转录病毒疗法的持续推广和预存预防的推广过程中被应用于高通量、低成本的HIVDR监测和监测方法。同样,PCR和NGS的改进导致了更高通量的单基因组测序,以检测完整的前病毒,并表征HIV整合位点和感染细胞的克隆扩增。综述:目前用于抗性监测的群体基因分型方法成本高,产量低。NGS与更简单的样本采集和存储基质(如干血点)相结合,在扩大全球HIVDR监测和患者监测方面具有相当大的潜力。最近,NGS用于识别人类基因组中HIV的整合位点并表征整合的HIV前病毒,可能有助于研究实验性“治疗性”干预对HIV宿主的影响。
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Future technologies for monitoring HIV drug resistance and cure.

Purpose of review: 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.

Recent findings: 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.

Summary: 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.

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