Although C/EBPc chimeras showed normal T and B cell development, the cytolytic functions of their splenic natural killer cells after stimulation with cytokines such as IL-12, IL-18 and IL-2 were significantly reduced

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 11118042” 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 PG-490 price 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 proportion of CD4+ T cells expressing CTLA-4 prior to treatment interruption, and a greater proportion of HIV-1 Gag-reactive CD4+ TNF-a+ cells expressing either CTLA-4 or PD-1. Viral suppression, however, was not sustained in the majority of subjects with initial virologic control. Participants with initial virologic suppression were found to have an initial immunologic benefit whereas non-suppressors had substantial CD4+ cell declines over the initial 16 weeks of the analytic treatment interruption. However, this initial viral control was not sustained in the majority of initial suppressors and was associated with a CD4+ cell decline over the subsequent 33 weeks. Potential explanations for the loss of viral control include the waning of vaccine-induced immune function over time and differing characteristics of the latent H