Severe infection with Mycobacterium avium is an undesirable, so-far incurable, complication of HIV infection in up to 50% of AIDS patients. This project's objective is to learn why AIDS patients are extraordinarily susceptible to M. avium. The knowledge should help prevent and cure this complication, and should also improve understanding of the pathogenesis and immunology of HIV infection. There are two important defects in AIDS native immunity to M. avium - lack of a serum constituent that blocks M. avium growth in cultured human monocytic phagocytes (MP), and unresponsiveness of MP to the blocker. These defects will be systematically studied with the in vitro model of M. avium growth in MP will be studied. The bacteria in the MP require a nutrient made by the MP from a pronutrient constituent of serum. Conversion of pronutrient to nutrient is blocked in normal MP by an inhibitor in normal serum. AIDS serum contains the pronutrient but lacks the inhibitor, and AIDS MP do not respond to the inhibitor. A defined serum substitute will be used. It resembles AIDS serum in containing the pronutrient but lacking the inhibitor. The pronutrient will be identified from among the known constituent(s) of normal serum makes the serum substitute inhibitory. The defect in AIDS MP will be analyzed by studying the responses of MP from subjects in various stages of HIV infection, compared with MP from normal subjects, to M. avium infection in normal and patient serum, an in serum substitute. The experimental model uses cultured human MP infected with virulent M. avium, where changes in concentration of colony-forming units of M. avium in the MP and their medium are measured at 0, 4, and 7 days after infection.
