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Acute HIV-1 infection viremia associate with rebound upon treatment interruption.

Authors :
Mdluli T
Li Y
Pinyakorn S
Reeves DB
Cardozo-Ojeda EF
Yates A
Intasan J
Tipsuk S
Phanuphak N
Sacdalan C
Colby DJ
Kroon E
Crowell TA
Thomas R
Robb ML
Ananworanich J
de Souza M
Phanuphak P
Stieh DJ
Tomaka FL
Trautmann L
Ake JA
Hsu DC
Francisco LV
Vasan S
Rolland M
Source :
Med (New York, N.Y.) [Med] 2022 Sep 09; Vol. 3 (9), pp. 622-635.e3. Date of Electronic Publication: 2022 Jul 22.
Publication Year :
2022

Abstract

Background: Analytic treatment interruption (ATI) studies evaluate strategies to potentially induce remission in people living with HIV-1 but are often limited in sample size. We combined data from four studies that tested three interventions (vorinostat/hydroxychloroquine/maraviroc before ATI, Ad26/MVA vaccination before ATI, and VRC01 antibody infusion during ATI).<br />Methods: The statistical validity of combining data from these participants was evaluated. Eleven variables, including HIV-1 viral load at diagnosis, Fiebig stage, and CD4 <superscript>+</superscript> T cell count were evaluated using pairwise correlations, statistical tests, and Cox survival models.<br />Findings: Participants had homogeneous demographic and clinical characteristics. Because an antiviral effect was seen in participants who received VRC01 infusion post-ATI, these participants were excluded from the analysis, permitting a pooled analysis of 53 participants. Time to viral rebound was significantly associated with variables measured at the beginning of infection: pre-antiretroviral therapy (ART) viral load (HR = 1.34, p = 0.022), time to viral suppression post-ART initiation (HR = 1.07, p < 0.001), and area under the viral load curve (HR = 1.34, p = 0.026).<br />Conclusions: We show that higher viral loads in acute HIV-1 infection were associated with faster viral rebound, demonstrating that the initial stage of HIV-1 infection before ART initiation has a strong impact on viral rebound post-ATI years later.<br />Funding: This work was supported by a cooperative agreement between the Henry M. Jackson Foundation for the Advancement of Military Medicine and the US Department of the Army (W81XWH-18-2-0040). This research was funded, in part, by the US National Institute of Allergy and Infectious Diseases (AAI20052001) and the I4C Martin Delaney Collaboratory (5UM1AI126603-05).<br />Competing Interests: Declaration of interests The views expressed are those of the authors and should not be construed to represent the positions of the US Army, the Department of Defense, the Department of Health and Human Services, or the Henry M. Jackson Foundation for the Advancement of Military Medicine. D.J.S. and F.L.T. are employees of Janssen Vaccines & Prevention and own stock and stock options in Johnson & Johnson. The other authors declare no competing interests. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.<br /> (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
2666-6340
Volume :
3
Issue :
9
Database :
MEDLINE
Journal :
Med (New York, N.Y.)
Publication Type :
Academic Journal
Accession number :
35870446
Full Text :
https://doi.org/10.1016/j.medj.2022.06.009