Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 Feb 13;15(1):21.
doi: 10.1186/s12977-018-0404-7.

Measuring replication competent HIV-1: advances and challenges in defining the latent reservoir

Zheng Wang  1 , Francesco R Simonetti  2 , Robert F Siliciano  3   4 , Gregory M Laird  2
Affiliations
Review

Measuring replication competent HIV-1: advances and challenges in defining the latent reservoir

Zheng Wang et al. Retrovirology. .

Abstract

Antiretroviral therapy cannot cure HIV-1 infection due to the persistence of a small number of latently infected cells harboring replication-competent proviruses. Measuring persistent HIV-1 is challenging, as it consists of a mosaic population of defective and intact proviruses that can shift from a state of latency to active HIV-1 transcription. Due to this complexity, most of the current assays detect multiple categories of persistent HIV-1, leading to an overestimate of the true size of the latent reservoir. Here, we review the development of the viral outgrowth assay, the gold-standard quantification of replication-competent proviruses, and discuss the insights provided by full-length HIV-1 genome sequencing methods, which allowed us to unravel the composition of the proviral landscape. In this review, we provide a dissection of what defines HIV-1 persistence and we examine the unmet needs to measure the efficacy of interventions aimed at eliminating the HIV-1 reservoir.

Keywords: HIV-1 persistence; Measuring HIV-1 latent reservoir; Replication-competent HIV-1.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Classification of HIV-1 DNA present in HIV-1 + individuals on suppressive ART. A decision tree describing the classification of HIV-1 DNA based on integration, genomic integrity/replication competence, transcription state, and ability to be induced by T cell activation. A complementary table is provided indicating which forms of persistent HIV-1 DNA are detected by common assays in the field. Hatched patterns indicate that the relevant assay detects only a subset of viruses in a given category
See this image and copyright information in PMC

References

    1. Chun TW, Finzi D, Margolick J, Chadwick K, Schwartz D, Siliciano RF. In vivo fate of HIV-1-infected T cells: quantitative analysis of the transition to stable latency. Nat Med. 1995;1:1284–1290. doi: 10.1038/nm1295-1284. - DOI - PubMed
    1. Chun TW, Carruth L, Finzi D, Shen X, DiGiuseppe JA, Taylor H, Hermankova M, Chadwick K, Margolick J, Quinn TC, et al. Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection. Nature. 1997;387:183–188. doi: 10.1038/387183a0. - DOI - PubMed
    1. Finzi D, Hermankova M, Pierson T, Carruth LM, Buck C, Chaisson RE, Quinn TC, Chadwick K, Margolick J, Brookmeyer R, et al. Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science. 1997;278:1295–1300. doi: 10.1126/science.278.5341.1295. - DOI - PubMed
    1. Wong JK, Hezareh M, Gunthard HF, Havlir DV, Ignacio CC, Spina CA, Richman DD. Recovery of replication-competent HIV despite prolonged suppression of plasma viremia. Science. 1997;278:1291–1295. doi: 10.1126/science.278.5341.1291. - DOI - PubMed
    1. Chun TW, Stuyver L, Mizell SB, Ehler LA, Mican JA, Baseler M, Lloyd AL, Nowak MA, Fauci AS. Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy. Proc Natl Acad Sci U S A. 1997;94:13193–13197. doi: 10.1073/pnas.94.24.13193. - DOI - PMC - PubMed

Publication types