Abstract

While current antiretroviral therapies are able to halt HIV-1 progression, they are not curative, as an interruption of treatment usually leads to viral rebound. The persistence of this stable HIV-1 latent reservoir forms the major barrier in HIV-1 cure research. The need for a better understanding of the mechanisms behind reservoir persistence resulted in the development of several novel assays allowing to perform an extensive in-depth characterization. The objective of this review is to present an overview of the current state-of-the-art PCR-based technologies to study the replication-competent HIV-1 reservoir. Here, we outline the advantages, limitations, and clinical relevance of different approaches. Future HIV-1 eradication studies would benefit from information-rich, high-throughput assays as they provide a more efficient and standardized way of characterizing the persisting HIV-1 reservoir.

Highlights

  • The introduction of antiretroviral therapy (ART) has turned once deadly HIV-1 infection into a manageable chronic disease, drawbacks include side effects, high costs, and requirement for lifelong adherence and accessibility to the medication [1]

  • As the search for new HIV-1 cure strategies has been highly pursued over the last decade, it has put an emphasis on the need to adequately evaluate their efficacy by establishing an accurate way to quantify and genetically characterize the reservoir

  • Many ongoing clinical trials aim to reduce and/or eliminate the viral reservoir but lack a comprehensive and standardized assay to retrieve this type of information, making it often difficult to compare studies as the outcome depends on the assay that was used

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Summary

Introduction

The introduction of antiretroviral therapy (ART) has turned once deadly HIV-1 infection into a manageable chronic disease, drawbacks include side effects, high costs, and requirement for lifelong adherence and accessibility to the medication [1]. A definitive cure is lacking, as ART interferes with the viral life cycle and halts viral replication but does not lead to HIV-1 eradication. An interruption of ART typically results in viral rebound due to the early establishment of a so-called latent “HIV-1 viral reservoir”. This reservoir remains unaffected by ART and consists of a small stable pool of infected cells harboring HIV-1 proviruses that are replication-competent, forming the major barrier to a cure [2]. Many ongoing clinical trials aim to reduce and/or eliminate the viral reservoir but lack a comprehensive and standardized assay to retrieve this type of information, making it often difficult to compare studies as the outcome depends on the assay that was used

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