Effect of analytical treatment interruption and reinitiation of antiretroviral therapy on HIV reservoirs and immunologic parameters in infected individuals.

PLoS Pathogens. 2018;14(1):e1006792 DOI 10.1371/journal.ppat.1006792


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Journal Title: PLoS Pathogens

ISSN: 1553-7366 (Print); 1553-7374 (Online)

Publisher: Public Library of Science (PLoS)

LCC Subject Category: Medicine: Internal medicine: Specialties of internal medicine: Immunologic diseases. Allergy | Science: Biology (General)

Country of publisher: United States

Language of fulltext: English

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Katherine E Clarridge

Jana Blazkova

Kevin Einkauf

Mary Petrone

Eric W Refsland

J Shawn Justement

Victoria Shi

Erin D Huiting

Catherine A Seamon

Guinevere Q Lee

Xu G Yu

Susan Moir

Michael C Sneller

Mathias Lichterfeld

Tae-Wook Chun


Peer review

Editorial Board

Instructions for authors

Time From Submission to Publication: 24 weeks


Abstract | Full Text

Therapeutic strategies aimed at achieving antiretroviral therapy (ART)-free HIV remission in infected individuals are under active investigation. Considering the vast majority of HIV-infected individuals experience plasma viral rebound upon cessation of therapy, clinical trials evaluating the efficacy of curative strategies would likely require inclusion of ART interruption. However, it is unclear what impact short-term analytical treatment interruption (ATI) and subsequent reinitiation of ART have on immunologic and virologic parameters of HIV-infected individuals. Here, we show a significant increase of HIV burden in the CD4+ T cells of infected individuals during ATI that was correlated with the level of plasma viral rebound. However, the size of the HIV reservoirs as well as immune parameters, including markers of exhaustion and activation, returned to pre-ATI levels 6-12 months after the study participants resumed ART. Of note, the proportions of near full-length, genome-intact and structurally defective HIV proviral DNA sequences were similar prior to ATI and following reinitiation of ART. In addition, there was no evidence of emergence of antiretroviral drug resistance mutations within intact HIV proviral DNA sequences following reinitiation of ART. These data demonstrate that short-term ATI does not necessarily lead to expansion of the persistent HIV reservoir nor irreparable damages to the immune system in the peripheral blood, warranting the inclusion of ATI in future clinical trials evaluating curative strategies.