Antibody-dependent cellular cytotoxicity (ADCC) is part of the natural immune response to infection with human immunodeficiency virus type 1 (HIV-1). While these responses may be beneficial to the host by eliminating infected cells, ADCC may, in addition, lyse uninfected CD4+ cells that have gp120 bound to the CD4 molecule. The cell-mediated cytotoxicity (CMC) assay measures the ability of natural killer (NK) cells from HIV-infected patients, that have gp120-specific antibodies bound to the FcgammaIII receptor, to lyse a gp120-adsorbed CEM.NKR cell target. Our preliminary studies support the hypothesis that ADCC may contribute to CD4 cell destruction. This is a laboratory and clinical study to test hypotheses relating the rate of CD4 depletion to in vitro measures of ADCC and viral load. This study will enroll a prospective clinical cohort to further evaluate these hypotheses. Preliminary studies also suggest that intrinsic differences may be present that distinguish the group of rapid CD4-decliners from a group with stable or rising CD4 percentages. The relevant components of CMC activity (gp120, antibody to gp120 and effector cell function) will be studied in patients in the prospective cohort, as well as in long-term non-progressors, seroconverters and those receiving treatment with antiretroviral agents or monoclonal antibodies.
