The goals of this research project are to determine the extent of antiviral immunity to Human Immunodeficiency Virus (HIV) in vivo, and to quantify this immunity by new in vitro immunological assays.
Specific Aim 1 is to use the viral and lymphocyte dynamics that occur after a short-term (12 weeks) interruption of antiviral therapy, termed a Diagnostic Treatment Interruption (DTI), to analyze the efficacy of immune-based therapies (IBT) for chronic infection by HIV. Two IBTs will be tested, therapeutic immunization with an HIV vaccine (canarypox, ALVAC, vCP1452), and daily low dose interleukin 2 (IL2) adjuvant therapy, in a 2 step, 2x2 factorial, randomized, controlled, phase II clinical trial of 92 subjects. IBTs will be administered to 4 distinct groups during 12 weeks of Step I, while during the 12 succeeding weeks of Step II, the extent of in vivo antiviral immune reactivity will be detrmined by the plateau """"""""trough"""""""" plasma HIV concentration, determined between weeks 8-1 2 after the DTI. Additional objectives are to determine whether viral relapse is prevented by any of the IBTs, as well as the duration of IBT control of viremia.
Specific Aim 2 is to use a short-term activation of peripheral blood mononuclear cells with mixtures of 15-20 amino acid peptides from each of the HIV gene products to determine the frequency of both CD4+ and CD8+ T lymphocytes capable of responding by expressing cell surface activation markers, and by producing cytokines (IL2, interferon-gamma, tumor necrosis factor-alpha) detectable by flow cytometry. The absolute concentratoins of HIV antigen-specific Cytokine Producing Lymphocyte precursors (CPLp) in each of the 4 IBT groups will be quantified before, and during both Steps I L II of the immunotherapy trial. The function of HIV-specific cells will be determine by quantifying the numbers of CPLp. Selected subjects will also be studied to relate the viral genotype with in vitro immune responsiveness.
The aim i s to test the hypothesis that IBTs will add therapeutic benefit to standard antiviral therapy, and that this can be quantified in vivo and in vitro. Thus, this project is designed to determine the capacity of IBTs to control HIV, and to develop laboratory assays that are predictive of effective HIV immunty.
