Tumor Necrosis Factor β and Soluble APO-1/Fas Independently Predict Progression to AIDS in HIV-Seropositive Patients

The relationship between serum concentration of different components of the nerve growth factor/tumor necrosis factor (TNF) receptor family, including soluble APO-1/Fas (sAPO-1/Fas) and progression of HIV infection, was analyzed in a case-control study of individuals selected from a cohort of HIV-seropositive patients who were progressing or not progressing to AIDS while being treated with nucleoside analogs. HIV-seronegative healthy controls were also analyzed. The results showed that, despite close matching for immunologic (CD4 cell count, beta2-microglobulin concentration) and virologic (p24 antigen, detection of HIV syncytium-inducing phenotype, plasma HIV viremia) parameters, the baseline serum concentrations of TNF-beta and sAPO-1/Fas were statistically different between progressing and nonprogressing patients. In addition, serum concentrations of TNF-beta and sAPO-1/Fas showed the strongest independent predictive power for progression to AIDS in a multivariate conditional logistic regression model. Because TNF-beta and Fas were suggested to be mediators of antigen-induced cell death (AICD) in HIV infection and sAPO-1/Fas was hypothesized to protect lymphocyte against AICD, these data suggest an important pathogenetic role for AICD in the progression of HIV infection.