GP120-DIRECTED ANTIBODY-DEPENDENT CELLULAR CYTOTOXICITY AS A MAJOR DETERMINANT OF THE RATE OF DECLINE IN CD4 PERCENTAGE IN HIV-1 DISEASE

Objective: To determine the relationship between the rate of CD4 perce ntage decline and two factors postulated to be associated with CD4 cel l destruction: circulating HIV-1 viral load and gp120-directed antibod y-dependent cellular cytotoxicity (ADCC). Design: Four women and 16 me n had serial determinations of CD4 percentage, gp120-directed ADCC act ivity [using the cell-mediated cytotoxicity (CMC) assay], natural kill er (NK) cell number, spontaneous NK lytic function, and plasma HIV-1 R NA. Methods: The rate of decline in CD4 percentage was modeled as a fu nction of gp120-directed ADCC activity and circulating HIV-1 RNA using Pearson correlation and multiple regression analyses. Results: All in dividuals had at least four CMC assays performed and two HIV-1 RNA pol ymerase chain reaction measurements over a median follow-up of 27 mont hs. Although the rate of CD4 percentage decline was associated with ei ther 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 betwe en CMC and HIV-1 RNA (r = -0.76, P < 0.0001). Mean CMC activity was as sociated with both mean percentage of circulating NK cells and mean sp ontaneous NK cell lysis. Conclusions: The ability of cells from HIV-in fected individuals to mediate gp120-directed ADCC, together with a suf ficient circulating viral load, define conditions under which rapid CD 4 cell destruction may occur. This relationship between viral load and an HIV-1-specific immune response lends important insights into the c entral causes of immunodeficiency in AIDS and suggests additional aven ues for therapeutic intervention.