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MAC: pathogenesis and treatment.




 

3rd Conf Retro and Opportun Infect. 1996 Jan 28-Feb 1;:166. Unique

Mac disease results from a complex interplay between virulence characteristics of MAC and host immune responses. Following inhalation of ingestion of MAC, virulent strains are able to adhere to and invade mucosal epithelial cells. Fibronectin, mannosyl-fucosyl and CR1 or CR3 receptor interactions, deposition of C'3, and activation of the alternate complement pathway, play key roles in the subsequent binding and update of MAC macrophages. MAC may resist oxidative killing by production of superoxide dismutase or inhibition of phagosome-lysosome fusion and acidification. IFN-gamma, TNF-a, GM-CSF, IL-1-a, IL-6, IL-10, IL-12 and TGF-beta each influence MAC pathogenesis. IL-12 indirectly affects MAC by stimulating IFN-gamma, GM-CSF and TNF-a production. IFN-gamma or TNF-a +/- other cytokines decrease intra-celluar growth of MAC. GM-CSF activates macrophages and with TNF-a reduces intracellular growth of MAC. IL-1-a, IL-6, IL-10 and TGF-beta increase intracellular MAC growth: IL-6 may down-regulate TNF receptor expression. After infection unrestricted MAC replication results in an initial, often asymptomatic mycobacteremia: dissemination leads to a heavy tissue burden with sustained bacteremia and overt symptoms. MAC disease should be treated with at least two drugs. Clarithromycin (CLA) or azithromycin are active primary drugs; ethambutol (EMB) added to CLA appears to delay the emergence of resistance. CLA regimens are superior to non-macrolide regimens, clofazimine appears to have minimal effect, and rifabutin, when added to CLA and EMB may enhance their efficacy. A response can be expected within 2-6 weeks. Relapse is common; the most effective salvage therapy or the role of immunomodulators is unclear.

Anti-Infective Agents/ADMINISTRATION & DOSAGE/THERAPEUTIC USE Azithromycin/ADMINISTRATION & DOSAGE/THERAPEUTIC USE Clarithromycin/ADMINISTRATION & DOSAGE/THERAPEUTIC USE Complement Pathway, Alternative Cytokines/METABOLISM Ethambutol/ADMINISTRATION & DOSAGE/THERAPEUTIC USE Human Macrophages/MICROBIOLOGY Mycobacterium avium Complex/METABOLISM/PATHOGENICITY Mycobacterium avium-intracellulare Infection/DRUG THERAPY/ *ETIOLOGY ABSTRACT



 




Information in this article was accurate in November 30, 1996. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.