Lungu Cynthia, Banga Riddhima, Gruters Rob A, Procopio Francesco A
Department of Viroscience, Erasmus University Medical Center, Rotterdam, Netherlands.
Department of Immunology and Allergy, Lausanne University Hospital, Lausanne, Switzerland.
Front Microbiol. 2021 Jun 15;12:686690. doi: 10.3389/fmicb.2021.686690. eCollection 2021.
The presence of a stable HIV-1 reservoir persisting over time despite effective antiretroviral suppression therapy precludes a cure for HIV-1. Characterizing and quantifying this residual reservoir is considered an essential prerequisite to develop and validate curative strategies. However, a sensitive, reproducible, cost-effective, and easily executable test is still needed. The quantitative viral outgrowth assay is considered the gold standard approach to quantify the reservoir in HIV-1-infected patients on suppressive ART, but it has several limitations. An alternative method to quantify the viral reservoir following the reactivation of latent HIV-1 provirus detects multiply-spliced RNA (msRNA) molecules by real-time PCR [ induced limiting dilution assay (TILDA)]. This article provides a perspective overview of the clinical relevance, various applications, recent advancements of TILDA, and how the assay has contributed to our understanding of the HIV-1 reservoir.
尽管有有效的抗逆转录病毒抑制疗法,但随着时间推移仍存在稳定的HIV-1病毒库,这使得HIV-1无法治愈。对这种残留病毒库进行特征描述和定量分析被认为是开发和验证治愈策略的必要前提。然而,仍然需要一种灵敏、可重复、经济高效且易于执行的检测方法。定量病毒生长测定法被认为是在接受抑制性抗逆转录病毒治疗的HIV-1感染患者中对病毒库进行定量的金标准方法,但它有几个局限性。一种在潜伏的HIV-1前病毒重新激活后对病毒库进行定量的替代方法是通过实时PCR检测多重剪接RNA(msRNA)分子[诱导极限稀释测定法(TILDA)]。本文对TILDA的临床相关性、各种应用、最新进展以及该测定法如何有助于我们理解HIV-1病毒库进行了前瞻性概述。