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HIV Reservoir: How to Measure It?

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Abstract

Purposeof Review

In the current quest for a complete cure for HIV/AIDS, the persistence of a long-lived reservoir of cells carrying replication-competent proviruses is the major challenge. Here, we describe the main elements and characteristics of several widely used assays of HIV latent reservoir detection.

Recent Findings

To date, researchers have developed several different HIV latent reservoir detection assays. Among them, the in vitro quantitative viral outgrowth assay (QVOA) has been the gold standard for assessing latent HIV-1 viral load. The intact proviral DNA assay (IPDA) based on PCR also demonstrated the predominance of defective viruses. However, these assays all have some drawbacks and may still be inadequate in detecting the presence of ultralow levels of latent virus in many patients who were initially thought to have been cured, but eventually showed viral rebound.

Summary

An accurate and precise measurement of the HIV reservoir is therefore needed to evaluate curative strategies, aimed to functional cure or sterilizing cure.

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Data Availability

The literature used and referenced in this study are all available in peer-reviewed journals and are publicly accessible.

Abbreviations

ART:

antiretroviral therapy

CA-RNA:

cell-associated viral RNA

ddPCR:

digital droplet PCR

ELISA:

enzyme-linked immunosorbent assay

FLIPS:

Full-Length Individual Proviral Sequencing

hmVOA:

humanized mouse-based HIV-1 viral outgrowth assay

IPDA:

intact proviral DNA assay

IS:

integration site

IUPM:

infectious units per million cells

MIP-seq:

matched integration site and proviral sequencing

msRNA:

multiple spliced RNA

mVOA:

murine viral outgrowth assay

PBMCs:

peripheral blood mononuclear cells

PCR:

polymerase chain reaction

PLWH:

people living with HIV

PMA:

phorbol 12-myristate 13-acetic acid

PRIP-seq:

parallel HIV-1 RNA, integration site, and proviral sequencing

QVOA:

quantitative viral outgrowth assay

STIP-Seq:

Simultaneous TCR, Integration site and Provirus sequencing

TILDA:

Tat/Rev Induced Limiting Dilution Assay

UNAIDS:

United Nations Programme on AIDS

WGA:

whole-genome amplification

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Funding

This work was supported by the Shanghai Municipal Healthy Commission (GWV-10.1-XK2); Shanghai Shenkang Hospital Development Center (SHDC2020RC6025); Shanghai Public Health Clinical Center, Fudan University (KY-GW-2021-45).

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Authors and Affiliations

  1. Scientific Research Center, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China

    Xinyu Zhang

  2. Department of Infectious Diseases and Immunology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China

    Jun Chen

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  1. Xinyu Zhang
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  2. Jun Chen
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Xinyu Zhang performed the literature search, prepared the figures, and wrote the manuscript. Chen Jun provided manuscript guidance and revision. All the authors read and approved the final manuscript.

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Correspondence to Jun Chen.

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Zhang, X., Chen, J. HIV Reservoir: How to Measure It?. Curr HIV/AIDS Rep 20, 29–41 (2023). https://doi.org/10.1007/s11904-023-00653-1

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