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

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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

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