Gp120-directed antibody-dependent cellular cytotoxicity as a major determinant of the rate of decline in CD4 percentage in HIV-1 disease.

Abstract

To determine the relationship between the rate of CD4 percentage decline and two factors postulated to be associated with CD4 cell destruction: circulating HIV-1 viral load and gp120-directed antibody-dependent cellular cytotoxicity (ADCC). Four women and 16 men had serial determinations of CD4 percentage gp120-directed ADCC activity [using the cell-mediated cytotoxicity (CMC) assay] natural killer (NK) cell number, spontaneous NK lytic function, and plasma HIV-1 RNA. The rate of decline in CD4 percentage was modeled as a function of gp120-directed ADCC activity and circulating HIV-1 RNA using Pearson correlation and multiple regression analyses. All individuals had at least four CMC assays performed and two HIV-1 RNA polymerase chain reaction measurements over a median follow-up of 27 months. Although the rate of CD4 percentage decline was associated with either CMC activity (r = -0.53, P = 0.02) or circulating HIV-1 RNA (r = -0.42, P = 0.07), it was strongly correlated with an interaction between CMC and HIV-1 RNA (r = -0.76, P < 0.0001). Mean CMC activity was associated with both mean percentage of circulating NK cells and mean spontaneous NK cell lysis. The ability of cells from HIV-infected individuals to mediate gp120-directed ADCC, together with a sufficient circulating viral load, define conditions under which rapid CD4 cell destruction may occur. This relationship between viral load and an HIV-1-specific immune response lends important insights into the central causes of immunodeficiency in AIDS and suggests additional avenues for therapeutic intervention.