MYCOBACTERIUM-AVIUM INFECTION IN HIV-1-INFECTED SUBJECTS INCREASES MONOKINE SECRETION AND IS ASSOCIATED WITH ENHANCED VIRAL LOAD AND DIMINISHED IMMUNE-RESPONSE TO VIRAL-ANTIGENS

The complex interaction between HIV-1 infection and Mycobacterium aviu m was studied. Viral burden was assessed, as well as immune response t o HIV-1 in the context of Myco. avium infections. We also examined ser um cytokine levels and cytokine release by blood mononuclear cells in HIV-1-infected subjects, infected or not with Myco. avium. Undetectabl e serum levels of IL-1, tumour necrosis factor-alpha (TNF-alpha) and I L-6 were found in normal controls and in groups I, II and III of HIV-1 l-infected subjects. Moderate levels of TNF-alpha, IL-1 and IL-6 were found in the sera of group IV patients. When group IV was subdivided i nto subjects with and without Myco. avium infections, subjects with My co. avium infections were shown to have higher serum levels of TNF-alp ha, IL-1 beta and IL-6 than those with other infections. Blood mononuc lear cells from controls and HIV subjects were stimulated with bacteri al lipopolysaccharide, and cytokine levels assessed. Cells from group II patients were shown to secrete normal levels of TNF-alpha and IL-6, and lower levels of IL-1 beta; group III subjects released higher lev els of IL-6. Patients in group IV had blood cells that released elevat ed levels of IL-6 and TNF-alpha, and lower levels of IL-1 beta. Group IV subjects with Myco. avium infections had blood cells that released higher levels of TNF-alpha, IL-6 and IL-1 than group IV subjects with other infections. Assessment of viral burden in cells of HIV-1-infecte d subjects revealed that Myco. avium-infected subjects had a higher le vel of virus burden and a lower level of lymphoproliferative response to an inactivated gp120-depleted HIV-1 antigen than AIDS subjects with other infections. These data suggest that Myco. avium infections in H IV-1-infected subjects hasten the progression of viral disease, enhanc e cytokine release and contribute to the anergy to viral antigens.