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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Title: Characteristics and Outcomes of Initial Virologic Suppressors during Analytic Treatment Interruption in a Therapeutic HIV-1 \(gag\) Vaccine Trial
Author: Brumme, Chanson J.; Lederman, Michael M.; Brumme, Zabrina L.; Wang, Hongying; Carrington, Mary; Medvik, Kathleen; Schooley, Robert T.; Li, Jonathan Zheng; Spritzle, John; Walker, Bruce David; Kuritzkes, Daniel Robert

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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.
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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
Published Version: doi:10.1371/journal.pone.0034134
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3316607/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:9807312

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