Plasma HIV Viral Rebound following Protocol-Indicated Cessation of ART Commenced in Primary and Chronic HIV Infection
Author(s)
Type
Journal Article
Abstract
Objectives: The magnitude of HIV viral rebound following ART cessation has consequences for clinical outcome and onward
transmission. We compared plasma viral load (pVL) rebound after stopping ART initiated in primary (PHI) and chronic HIV
infection (CHI).
Design: Two populations with protocol-indicated ART cessation from SPARTAC (PHI, n = 182) and SMART (CHI, n = 1450)
trials.
Methods: Time for pVL to reach pre-ART levels after stopping ART was assessed in PHI using survival analysis. Differences in
pVL between PHI and CHI populations 4 weeks after stopping ART were examined using linear and logistic regression.
Differences in pVL slopes up to 48 weeks were examined using linear mixed models and viral burden was estimated
through a time-averaged area-under-pVL curve. CHI participants were categorised by nadir CD4 at ART stop.
Results: Of 171 PHI participants, 71 (41.5%) rebounded to pre-ART pVL levels, at a median of 50 (95% CI 48–51) weeks after
stopping ART. Four weeks after stopping treatment, although the proportion with pVL$400 copies/ml was similar (78% PHI
versus 79% CHI), levels were 0.45 (95% CI 0.26–0.64) log10 copies/ml lower for PHI versus CHI, and remained lower up to 48
weeks. Lower CD4 nadir in CHI was associated with higher pVL after ART stop. Rebound for CHI participants with CD4 nadir
.500 cells/mm3 was comparable to that experienced by PHI participants.
Conclusions: Stopping ART initiated in PHI and CHI was associated with viral rebound to levels conferring increased
transmission risk, although the level of rebound was significantly lower and sustained in PHI compared to CHI.
transmission. We compared plasma viral load (pVL) rebound after stopping ART initiated in primary (PHI) and chronic HIV
infection (CHI).
Design: Two populations with protocol-indicated ART cessation from SPARTAC (PHI, n = 182) and SMART (CHI, n = 1450)
trials.
Methods: Time for pVL to reach pre-ART levels after stopping ART was assessed in PHI using survival analysis. Differences in
pVL between PHI and CHI populations 4 weeks after stopping ART were examined using linear and logistic regression.
Differences in pVL slopes up to 48 weeks were examined using linear mixed models and viral burden was estimated
through a time-averaged area-under-pVL curve. CHI participants were categorised by nadir CD4 at ART stop.
Results: Of 171 PHI participants, 71 (41.5%) rebounded to pre-ART pVL levels, at a median of 50 (95% CI 48–51) weeks after
stopping ART. Four weeks after stopping treatment, although the proportion with pVL$400 copies/ml was similar (78% PHI
versus 79% CHI), levels were 0.45 (95% CI 0.26–0.64) log10 copies/ml lower for PHI versus CHI, and remained lower up to 48
weeks. Lower CD4 nadir in CHI was associated with higher pVL after ART stop. Rebound for CHI participants with CD4 nadir
.500 cells/mm3 was comparable to that experienced by PHI participants.
Conclusions: Stopping ART initiated in PHI and CHI was associated with viral rebound to levels conferring increased
transmission risk, although the level of rebound was significantly lower and sustained in PHI compared to CHI.
Date Issued
2012-08-31
Date Acceptance
2012-07-26
Citation
PLoS ONE, 2012, 7 (8)
ISSN
1932-6203
Publisher
Public Library of Science
Journal / Book Title
PLoS ONE
Volume
7
Issue
8
Copyright Statement
© Hamlyn et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Sponsor
National Institute for Health Research
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000308221300025&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
NF-SI-0507-10313
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
MULTIDISCIPLINARY SCIENCES
EARLY ANTIRETROVIRAL THERAPY
CD4(+) T-CELLS
TRANSMISSION
INTERRUPTION
RESERVOIR
ERADICATION
INITIATION
TRIAL
VIRUS
TREAT
Adult
Anti-HIV Agents
CD4 Lymphocyte Count
Chronic Disease
Female
HIV
HIV Infections
Humans
Male
Middle Aged
Viral Load
Withholding Treatment
INSIGHT SMART and SPARTAC Investigators
MD Multidisciplinary
General Science & Technology
Publication Status
Published
Article Number
ARTN e43754