318-W. Augmentation of HIV-1-Specific Memory Subsets of T Lymphocytes and Decrease of Immune Activation in HIV-1+ Individuals Treated with a Therapeutic Vaccine plus Antiretrovirals: Impact on Viral Load

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Session 50 Poster Session
Therapeutic Vaccine Studies
Session Time: 4:30-6:30 pm
Room 4E-F

318-W.

Augmentation of HIV-1-Specific Memory Subsets of T Lymphocytes and Decrease of Immune Activation in HIV-1+ Individuals Treated with a Therapeutic Vaccine plus Antiretrovirals: Impact on Viral Load
E. Fernandez-Cruz*, J. Navarro, M. L. Abad, L. Díaz-Muñoz, C. Cantó, J. Carbone, S. Moreno, B. Clotet, J. Pérez Molina, J. M. Gatell, and M. Munoz-Fernandez for the Spanish 2102 Team
Univ. Hosp. Gregorio Marañon, Madrid, Spain

Background: We examined the immunomodulatory efficacy of a HIV-1 therapeutic vaccine (an inactivated gp120-depleted HIV-1 immunogen in IFA, REMUNETM) in 243 HIV+ chronically infected subjects while receiving either ART or HAART in a 3-year, double-blind, placebo (IFA)-controlled trial.
Methods: We have studied functional subsets of CD4+ and CD8+ T-cells, lymphoproliferative responses (LPR), and CTL responses to HIV-1 antigens in a subset of 54 HIV+ subjects.
Results: A significant increase of CD8 memory T cells (CD8+CD45RO+) was observed in Remune-Group (n=27) as compared to IFA-Group (n=27) (p<0.05). We observed a lower decrease of activated (CD4+HLA-DR+, CD4+CD38+DR+), and memory-activated T cells (CD4+CD45RO+DR+, CD8+CD45RO+CD38+) in Remune-Group in response to antiretrovirals as compared to IFA-Group (p<0.05). We found a positive correlation between activated and memory-activated CD4+ T cells with viral load in IFA-Group (CD4+CD38+DR+, CD4+CD45RO+DR+, r=-0.60 and r=0.44, p<0.05), but not in Remune-Group. Effector CD8+ T cells (CD8+CD57+ and CD8+CD28-CD57+) correlated negatively with CD4+ T cells in IFA-Group (r=-0.60, and r=-0.54, p<0.05), but not in Remune-Group. LPR to HIV-1 antigens correlated with HIV-Gag/pol-specific memory CTLs (r=0.498, p<0.05 for CTL precursors, and r=0.686, p<0.005 for Lytic Units), strongly increased in Remune-Group (n=13) as compared to IFA-Group (n=11). A significant increase in CD8+CD11b+ T-cells and a significant decrease in CD8+HLADR+ T-cells was only found in Remune-treated patients who developed high HIV-specific CTLs (p<0.05 and p<0.005). Only the Remune-Group showed a significant negative correlation between Gag/pol-specific memory CTL precursors and viral load (r=-0.58, p<0.05). Interestingly, the effect of Remune in maintaining virologic suppression was impacted by baseline viral load and CD4 in-patients on ART or HAART (Cox Regression Model, p = 0.034).
Conclusions: The results show that therapeutic vaccination decreases immune system activation and enhances immune responses to HIV that correlated with viral load.