KINETICS OF GAG-SPECIFIC CYTOTOXIC T-LYMPHOCYTE RESPONSES DURING THE CLINICAL COURSE OF HIV-1 INFECTION - A LONGITUDINAL ANALYSIS OF RAPID PROGRESSORS AND LONG-TERM ASYMPTOMATICS

To gain more insight into the role of HIV-1-specific cytotoxic T lymphocytes (CTL) in the pathogenesis of AIDS, we investigated temporal relations between HIV-1 Gag-specific precursor CTL. (CTLp), HIV-1 viral load, CD4(+) T cell counts, and T cell function. Six HIV-1-infected subjects, who were asymptomatic for more than 8 yr with CD4(+) counts >500 cells/mm(3), were compared with six subjects who progressed to AIDS within 5 yr after HIV-1 seroconversion. In the long-term asymptomatics, persistent HIV-1 Gag-specific CTL responses and very low numbers of HIV-1-infected CD4(+) T cells coincided with normal and stable CD4(+) counts and preserved CD3 mAb-induced T cell reactivity for more than 8 yr. In five out of six rapid progressors Gag-specific CTLp were also detected. However, early in infection the number of circulating HIV-1-infected CD4(+) T cells increased despite strong and mounting Gag-specific CTL responses. During subsequent clinical progression to AIDS, loss of Gag-specific CTLp coincided with precipitating CD4(+) counts and severe deterioration of T cell function. The possible relationships of HIV-1 Gag-specific CTLp to disease progression are discussed.