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dc.contributor.authorBrumme, Chanson J.
dc.contributor.authorLederman, Michael M.
dc.contributor.authorBrumme, Zabrina L.
dc.contributor.authorWang, Hongying
dc.contributor.authorCarrington, Mary
dc.contributor.authorMedvik, Kathleen
dc.contributor.authorSchooley, Robert T.
dc.contributor.authorLi, Jonathan Zheng
dc.contributor.authorSpritzle, John
dc.contributor.authorWalker, Bruce David
dc.contributor.authorKuritzkes, Daniel Robert
dc.date.accessioned2012-10-26T15:01:50Z
dc.date.issued2012
dc.identifier.citationLi, 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.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:9807312
dc.description.abstractBackground: 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 NCT00080106en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0034134en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3316607/pdf/en_US
dash.licenseLAA
dc.subjectHIVen_US
dc.subjectbiologyen_US
dc.subjectmicrobiologyen_US
dc.subjectvirologyen_US
dc.subjectmedicineen_US
dc.subjectclinical immunologyen_US
dc.subjectimmunityen_US
dc.subjectvaccinationen_US
dc.subjectinfectious diseasesen_US
dc.subjectviral diseasesen_US
dc.titleCharacteristics and Outcomes of Initial Virologic Suppressors during Analytic Treatment Interruption in a Therapeutic HIV-1 \(gag\) Vaccine Trialen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorWalker, Bruce David
dc.date.available2012-10-26T15:01:50Z
dc.identifier.doi10.1371/journal.pone.0034134*
dash.authorsorderedfalse
dash.contributor.affiliatedKuritzkes, Daniel
dash.contributor.affiliatedLi, Jonathan
dash.contributor.affiliatedWalker, Bruce
dc.identifier.orcid0000-0001-6122-9245


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