Characteristics and Outcomes of Initial Virologic Suppressors during Analytic Treatment Interruption in a Therapeutic HIV-1 \(gag\) Vaccine Trial

Characteristics and Outcomes of Initial Virologic Suppressors during Analytic Treatment Interruption in a Therapeutic HIV-1 \(gag\) Vaccine Trial

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Characteristics and Outcomes of Initial Virologic Suppressors during Analytic Treatment Interruption in a Therapeutic HIV-1 \(gag\) Vaccine Trial

dc.contributor.author	Brumme, Chanson J.
dc.contributor.author	Lederman, Michael M.
dc.contributor.author	Brumme, Zabrina L.
dc.contributor.author	Wang, Hongying
dc.contributor.author	Carrington, Mary
dc.contributor.author	Medvik, Kathleen
dc.contributor.author	Schooley, Robert T.
dc.contributor.author	Li, Jonathan Zheng
dc.contributor.author	Spritzle, John
dc.contributor.author	Walker, Bruce David
dc.contributor.author	Kuritzkes, Daniel Robert
dc.date.accessioned	2012-10-26T15:01:50Z
dc.date.issued	2012
dc.identifier.citation	Li, Jonathan Z., Chanson J. Brumme, Michael M. Lederman, Zabrina L. Brumme, Hongying Wang, John Spritzler, Mary Carrington, et al. 2012. Characteristics and outcomes of initial virologic suppressors during analytic treatment interruption in a therapeutic HIV-1 \(gag\) vaccine trial. PLoS ONE 7(3): e34134.	en_US
dc.identifier.issn	1932-6203	en_US
dc.identifier.uri	http://nrs.harvard.edu/urn-3:HUL.InstRepos:9807312
dc.description.abstract	Background: In the placebo-controlled trial ACTG A5197, a trend favoring viral suppression was seen in the HIV-1-infected subjects who received a recombinant Ad5 HIV-1 \(gag\) vaccine. Objective: To identify individuals with initial viral suppression (plasma HIV-1 RNA set point <3.0 \(log_{10}\) copies/ml) during the analytic treatment interruption (ATI) and evaluate the durability and correlates of virologic control and characteristics of HIV sequence evolution. Methods: HIV-1 \(gag\) and \(pol\) RNA were amplified and sequenced from plasma obtained during the ATI. Immune responses were measured by flow cytometric analysis and intracellular cytokine expression assays. Characteristics of those with and without initial viral suppression were compared using the Wilcoxon rank sum and Fisher's exact tests. Results: Eleven out of 104 participants (10.6%) were classified as initial virologic suppressors, nine of whom had received the vaccine. Initial virologic suppressors had significantly less CD4+ cell decline by ATI week 16 as compared to non-suppressors (median 7 CD4+ cell gain vs. 247 CD4+ cell loss, P = 0.04). However, of the ten initial virologic suppressors with a pVL at ATI week 49, only three maintained pVL <3.0 log10 copies/ml. HIV-1 Gag-specific CD4+ interferon-γ responses were not associated with initial virologic suppression and no evidence of vaccine-driven HIV sequence evolution was detected. Participants with initial virologic suppression were found to have a lower percentage of CD4+ CTLA-4+ cells prior to treatment interruption, but a greater proportion of HIV-1 Gag-reactive CD4+ TNF-α+ cells expressing either CTLA-4 or PD-1. Conclusions: Among individuals participating in a rAd5 therapeutic HIV-1 \(gag\) vaccine trial, initial viral suppression was found in a subset of patients, but this response was not sustained. The association between CTLA-4 and PD-1 expression on CD4+ T cells and virologic outcome warrants further study in trials of other therapeutic vaccines in development. Trial Registration: ClinicalTrials.gov NCT00080106	en_US
dc.language.iso	en_US	en_US
dc.publisher	Public Library of Science	en_US
dc.relation.isversionof	doi:10.1371/journal.pone.0034134	en_US
dc.relation.hasversion	http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3316607/pdf/	en_US
dash.license	LAA
dc.subject	HIV	en_US
dc.subject	biology	en_US
dc.subject	microbiology	en_US
dc.subject	virology	en_US
dc.subject	medicine	en_US
dc.subject	clinical immunology	en_US
dc.subject	immunity	en_US
dc.subject	vaccination	en_US
dc.subject	infectious diseases	en_US
dc.subject	viral diseases	en_US
dc.title	Characteristics and Outcomes of Initial Virologic Suppressors during Analytic Treatment Interruption in a Therapeutic HIV-1 \(gag\) Vaccine Trial	en_US
dc.type	Journal Article	en_US
dc.description.version	Version of Record	en_US
dc.relation.journal	PLoS ONE	en_US
dash.depositing.author	Walker, Bruce David
dc.date.available	2012-10-26T15:01:50Z