HIV-1 latent reservoir size and diversity are stable following brief treatment interruption.

TitleHIV-1 latent reservoir size and diversity are stable following brief treatment interruption.
Publication TypeJournal Article
Year of Publication2018
AuthorsD Salantes B, Zheng Y, Mampe F, Srivastava T, Beg S, Lai J, Li JZ, Tressler RL, Koup RA, Hoxie J, Abdel-Mohsen M, Sherrill-Mix S, McCormick K, E Overton T, Bushman FD, Learn GH, Siliciano RF, Siliciano JM, Tebas P, Bar KJ
JournalJ Clin Invest
Volume128
Issue7
Pagination3102-3115
Date Published2018 Jul 02
ISSN1558-8238
Abstract

BACKGROUND: The effect of a brief analytical treatment interruption (ATI) on the HIV-1 latent reservoir of individuals who initiate antiretroviral therapy (ART) during chronic infection is unknown.

METHODS: We evaluated the impact of transient viremia on the latent reservoir in participants who underwent an ATI and at least 6 months of subsequent viral suppression in a clinical trial testing the effect of passive infusion of the broadly neutralizing Ab VRC01 during ATI.

RESULTS: Measures of total HIV-1 DNA, cell-associated RNA, and infectious units per million cells (IUPM) (measured by quantitative viral outgrowth assay [QVOA]) were not statistically different before or after ATI. Phylogenetic analyses of HIV-1 env sequences from QVOA and proviral DNA demonstrated little change in the composition of the virus populations comprising the pre- and post-ATI reservoir. Expanded clones were common in both QVOA and proviral DNA sequences. The frequency of clonal populations differed significantly between QVOA viruses, proviral DNA sequences, and the viruses that reactivated in vivo.

CONCLUSIONS: The results indicate that transient viremia from ATI does not substantially alter measures of the latent reservoir, that clonal expansion is prevalent within the latent reservoir, and that characterization of latent viruses that can reactivate in vivo remains challenging.

TRIAL REGISTRATION: ClinicalTrials.gov NCT02463227FUNDING. Funding was provided by the NIH.

DOI10.1172/JCI120194
Alternate JournalJ. Clin. Invest.
PubMed ID29911997
PubMed Central IDPMC6026010
Grant ListP30 AI027767 / AI / NIAID NIH HHS / United States
UM1 AI126619 / AI / NIAID NIH HHS / United States
U01 AI069534 / AI / NIAID NIH HHS / United States
UM1 AI069534 / AI / NIAID NIH HHS / United States
P30 AI045008 / AI / NIAID NIH HHS / United States
R21 AI118431 / AI / NIAID NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI126611 / AI / NIAID NIH HHS / United States
UM1 AI069452 / AI / NIAID NIH HHS / United States
U01 AI069452 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States