A humanized mouse-based HIV-1 viral outgrowth assay with higher sensitivity than in vitro qVOA in detecting latently infected cells from individuals on ART with undetectable viral loads

一种基于人源化小鼠的 HIV-1 病毒生长试验,其灵敏度比体外 qVOA 更高,可用于检测接受 ART 且病毒载量无法检测的个体中的潜在感染细胞

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作者:Paige Charlins, Kimberly Schmitt, Leila Remling-Mulder, Louise E Hogan, Emily Hanhauser, Kristen S Hobbs, Frederick Hecht, Steven G Deeks, Timothy J Henrich, Ramesh Akkina

Abstract

Assays that can verify full viral eradication are essential in the context of achieving a cure for HIV/AIDS. In vitro quantitative viral out growth assays (qVOA) are currently the gold standard for measuring latent HIV-1 but these assays often fail to detect very low levels of replication-competent virus. Here we investigated an alternative in vivo approach for sensitive viral detection using humanized mice (hmVOA). Peripheral blood CD4+ T cell samples from HIV subjects on stable ART with undetectable viral loads by RT-PCR were first assayed by in vitro qVOA. Corresponding patient samples in which no virus was detected by qVOA were injected into humanized mice to allow viral outgrowth. Of the five qVOA virus negative samples, four gave positive viral outgrowth in the hmVOA assay suggesting that it is more sensitive in detecting latent HIV-1.

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