rences 212141-51-0 supplier between initial virologic suppressors and non-suppressors. Immunologic Factors Associated with Initial Virologic Suppression There was no significant difference between initial virologic suppressors and non-suppressors in the CD4 T-cell ” count at study entry. In the initial A5197 analysis, an inverse association was seen between the ATI set point viral load and the number of HIV-1 Gag-specific CD4 IFN-c-producing CD4 T cells at study weeks 8 and 38. 4 Viral Suppression after Therapeutic Vaccination There were no significant differences between initial virologic suppressors and non-suppressors in the number of HIV-1 Gagspecific IFN-c-producing CD4 T-cells at week 8 or 38, or Gag-specific IFN-c-producing CD8 T-cells. Similarly, no significant differences were detected between initial virologic suppressors and “8549627 non-suppressors in the number of subjects who had an increase in HIV-1 Gag-specific IFN-c-producing CD4 and CD8 T-cells from study entry to week 38. Thirty percent of initial virologic suppressors had a significant increase in the number of CD4 IFN-c-producing cells between baseline and week 38 as compared with 35% non-suppressors. Fifty percent of initial virologic suppressors had a significant increase in the number of CD8 IFN-c-producing cells as compared with 38% of non-suppressors. The number of HIV-1 Gag-specific CD4 IFN-c-producing cells detected was associated with vaccination status, but not with status of initial virologic suppression. There were no differences in the magnitude of HIV-1 Gag-specific CD4 IFN-c-producing cells between vaccinated participants with or without initial virologic suppression. In addition, vaccinated participants regardless of status of initial virologic suppression were found to have higher levels of HIV-1 Gag-specific IFN-c-producing cells at week 8 compared to initial non-suppressors who had received placebo. These results indicate that the magnitude of in vitro CD4 IFN-c responses to HIV-1 Gag peptides may have been influenced by therapeutic vaccination, but was not clearly correlated with initial virologic suppression. The association of initial virologic suppression with expression of the immunomodulatory molecules CTLA-4 and PD-1 on CD4 and CD8 cells expressing either TNF-a, IFN-c, or IL-2 were evaluated in a subset of participants at both study entry and study week 38. At week 38, participants with initial virologic suppression had significantly lower proportions of CD4 T cells expressing CTLA-4. No significant differences were seen in the expression of CD4 PD-1 T cells between those with and without initial virologic suppression. However, participants with initial virologic suppression had a significantly higher percentage of Gag-specific CD4 TNF-a cells expressing either CTLA-4 or PD-1. No significant differences were seen between the groups in either the expression of other cytokines in CD4 T cells or in any CD8 T cell populations. Discussion In ACTG A5197, vaccination with a rAd5 HIV-1 gag therapeutic vaccine was associated with increased HIV-specific T-cell activation and a trend towards improved virologic control during the analytic treatment interruption. In this follow-up study, we describe 11 subjects with viral load set point under 3.0 log10 copies/ml including 9 subjects who received the vaccine. No virologic differences were identified in participants with and without initial virologic suppression, but those with initial virologic suppression were found to have a lower pro
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