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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.

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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
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