Tumor necrosis factor beta 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.
Viral Hepatitis and AIDS Study Group, Departamento de Medicina Interna, Hospital Universitario Virgen del Rocio, Seville, Spain.
F J
FJ
Medrano
M
M
Leal
D
D
Arienti
C
C
Rey
A
A
Zagliani
Y
Y
Torres
A
A
Sanchez-Quijano
E
E
Lissen
M
M
Clerici
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology / Q000503:physiopathology / Q000821:virology; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006679:HIV Seropositivity / Q000097:blood* / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D006801:Humans; D008233:Lymphotoxin-alpha / Q000097:blood*; D008297:Male; D011237:Predictive Value of Tests; D012044:Regression Analysis; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D012995:Solubility; D015215:Zidovudine / Q000627:therapeutic use; D001613:beta 2-Microglobulin / Q000032:analysis; D019014:fas Receptor / Q000097:blood*
D019380:Anti-HIV Agents; D015415:Biomarkers; D008233:Lymphotoxin-alpha; D018894:Reverse Transcriptase Inhibitors; D001613:beta 2-Microglobulin; D019014:fas Receptor; D015215:Zidovudine