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243 Therapeutic Immunization with REMUNE Alters Kinetics of Viral Rebound after Analytical Therapy Interruption
R. P. Bucy*1, R. Moss2, M. Gersten3, and the 806A Study Team
1Univ. of Alabama at Birmingham, USA; 2Immune Response Corp., Carlsbad, CA, USA; and 3Agouron Pharmaceuticals, La Jolla, CA, USA
Background: The benefit of therapeutic immunization may be most clearly determined by analyzing the kinetics of viral rebound when patients stop all antiretroviral medications.
Methods: Subjects from a randomized adjuvant-controlled REMUNE vaccine trial designed to detect clinical end-points, who had maintained plasma HIV RNA <50 c/ml for 6 months prior to entry, underwent a planned 6-week analytical therapy interruption (ATI). The double-blind structure of the parent study was maintained and 20 REMUNE and 8 IFA subjects were enrolled. Lymphocyte proliferation assay (LPA) responses and the frequency of cells producing IL-2 or IFN-gamma after HIV antigen stimulation were measured.
Results: The slope of the initial rise in plasma vRNA was significantly slower (0.16 vs. 0.21 log10 copies/day) in the REMUNE vs. control group (p < 0.05). The peak and post peak low viral loads off therapy were lower in the REMUNE group, but this difference was not statistically significant. Of patients who remained off HAART or who restarted HAART after the peak viral load had been attained, 5 of 15 in the Remune group vs. 1 of 6 in the control group had a post peak low of <5,000 c/ml. Although the LPA response to p24 antigen did not correlate with indices of viral rebound, the frequency of cells that produce IFN-gamma when stimulated with either p24 or vaccinia virus constructs expressing several HIV proteins was significantly increased in the REMUNE group. Both IL-2 and IFN-gamma frequencies were higher in subjects with a post peak low <5,000 c/ml, but this association was not statistically significant. By flow cytometry, the frequency of blood CD4 T cells fell, whereas CD8 T cells rose during the ATI; both returned to baseline values when therapy was re-started.
Conclusions: Therapeutic immunization with REMUNE increases both CD4 and CD8 T-cell immunity to HIV antigens and alters the kinetics of viral rebound during ATI.
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