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Post-treatment control or treated controllers? Viral remission in treated and untreated primary HIV infection

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Title: Post-treatment control or treated controllers? Viral remission in treated and untreated primary HIV infection
Authors: Martin, GE
Gossez, M
Williams, JP
Stohr, W
Meyerowitz, J
Leitman, EM
Goulder, P
Porter, K
Fidler, S
Frater, J
Item Type: Journal Article
Abstract: Objective(s): An HIV cure will impose aviraemia that is sustained following the withdrawal of antiretroviral therapy (ART). Understanding the efficacy of novel interventions aimed at curing HIV requires characterization of both natural viral control and the effect of ART on viral control after treatment interruption. Design: Analysis of transient viral control in recent seroconverters in the Short Pulse AntiRetroviral Therapy at Acute Seroconversion trial. Methods: We compared untreated and treated HIV seroconverters (n = 292) and identified periods of control (plasma HIV RNA < 400 copies/ml for >=16 weeks off therapy) in 7.9% of ART-naive participants, and in 12.0% overall. HIV DNA was measured by qPCR, and HIV-specific CD8+ responses were measured by enzyme-linked immunosorbent spot assay (ELISpot). T-cell activation and exhaustion were measured by flow cytometry. Results: At baseline, future controllers had lower HIV DNA, lower plasma HIV RNA, higher CD4+ : CD8+ ratios (all P < 0.001) and higher CD4+ cell counts (P < 0.05) than noncontrollers. Among controllers, the only difference between the untreated and those who received ART was higher baseline HIV RNA in the latter (P = 0.003), supporting an added ART effect. Conclusion: Consideration of spontaneous remission in untreated individuals will be critical to avoid overestimating the effect size of new interventions used in HIV cure studies.
Issue Date: 20-Feb-2017
Date of Acceptance: 30-Nov-2016
URI: http://hdl.handle.net/10044/1/45719
DOI: https://dx.doi.org/10.1097/QAD.0000000000001382
ISSN: 0269-9370
Publisher: LIPPINCOTT WILLIAMS & WILKINS
Start Page: 477
End Page: 484
Journal / Book Title: AIDS
Volume: 31
Issue: 4
Copyright Statement: © 2017 Wolters Kluwer Health, Inc. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0
Sponsor/Funder: Imperial College Healthcare NHS Trust- BRC Funding
Medical Research Council (MRC)
St Marys Development Trust
MRC DCS
Medical Research Council (MRC)
Medical Research Council (MRC)
British HIV Association (BHIVA)
Merck Sharp & Dohme Ltd.
Funder's Grant Number: RDA02 79560
MR/L00528X/1
N/A
n/a
MR/N001265/1
N/A
8101898808
Keywords: Science & Technology
Life Sciences & Biomedicine
Immunology
Infectious Diseases
Virology
antiretroviral therapy
ELISpot
HIV
HIV DNA
natural history
post-treatment control
T lymphocytes
TRANSIENT ANTIRETROVIRAL TREATMENT
T-CELL-ACTIVATION
HLA CLASS-I
TREATMENT INTERRUPTION
CLINICAL-TRIAL
IMMUNE CONTROL
THERAPY
RESERVOIR
SIZE
SEROCONVERSION
06 Biological Sciences
11 Medical And Health Sciences
17 Psychology And Cognitive Sciences
Publication Status: Published
Appears in Collections:Department of Medicine
Faculty of Medicine



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