LOW T-CELL RESPONSES TO CD3 PLUS CD28 MONOCLONAL-ANTIBODIES ARE PREDICTIVE OF DEVELOPMENT OF AIDS

Objective: Decreased T-cell reactivity in vitro is strongly associated with progression to AIDS and low CD4+ T-cell numbers. Low T-cell resp onses in vitro induced by CD3 monoclonal antibody (mAb) are predictive for progression to AIDS independent of low CD4+ T-cell counts and hig h HIV-1 RNA levels. We developed a whole-blood lymphocyte culture syst em in which T cells were stimulated by a combination of CD3 and CD28 m AB. Combined stimulation of CD28, a costimulatory molecule, and CD3 co nsiderably enhances T-cell responses in vitro and reduces variation co efficients, which may increase the prognostic power of T-cell response s. Design: A prospective study of HIV-l-infected homosexual men follow ed for 35 months. Methods: The predictive value of low T-cell response s to CD3 plus CD28 mAb relative to low CD4+ T-cell counts, high HIV-1 RNA levels and the presence of syncytium-inducing (SI) HIV-1 variants was evaluated longitudinally in 202 HIV-1-infected homosexual men foll owed for 35 months. Results: In multivariate analysis, decreased T-cel l responses at baseline were predictive of development of AIDS, indepe ndent of law CD4+ T-cell numbers and high HIV-1 RNA levels. In a time- dependent model, HIV-1 RNA levels lost their predictive value, whereas low T-cell responses, low CD4+ T-cell numbers and the presence of SI HIV-1 variants independently predicted AIDS. Conclusions: These data d emonstrate that combined use of virological and immunological markers may be useful in monitoring disease progression and response to antire troviral therapy. (C) 1998 Lippincott Williams & Wilkins.