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Retrovirology. 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.

Author information

1
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
2
Department of Medicine, Johns Hopkins University School of Medicine, Room 879, Edward D. Miller Research Building, 733 N. Broadway, Baltimore, MD, 21205, USA.
3
Department of Medicine, Johns Hopkins University School of Medicine, Room 879, Edward D. Miller Research Building, 733 N. Broadway, Baltimore, MD, 21205, USA. rsiliciano@jhmi.edu.
4
Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. rsiliciano@jhmi.edu.

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

PMID:
29433524
PMCID:
PMC5810003
DOI:
10.1186/s12977-018-0404-7
[Indexed for MEDLINE]
Free PMC Article

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