Current and investigational therapies for AIDS-associated Mycobacterium avium complex disease.

The epidemiology, pathogenesis, clinical manifestations, and treatment of Mycobacterium avium complex (MAC) infection are reviewed. MAC infection is one of the most common infections in AIDS patients. Its pathogenesis is poorly understood, but it is believed to develop by gastrointestinal colonization followed by systemic invasion. The relatively poor response to treatment may be partly accounted for by the tremendous mycobacterial load present by the time patients develop systemic symptoms. Clinically, MAC infection is difficult to differentiate from the signs and symptoms of AIDS or from other opportunistic infections. Signs and symptoms include fever, malaise, anorexia, night sweats, and weight loss; diarrhea and abdominal pain may also be present. There is no established therapy for MAC infection, although combinations of three to five antimicrobial agents are typically used. There has been consistently poor correlation between in vitro results and in vivo outcomes in the treatment of MAC infection. Currently, the role of treatment is mainly to suppress the progression of infection and to relieve symptoms. Recent in vitro studies and animal studies have revealed possible alternative agents and combinations of agents (e.g., macrolide antibiotics, quinolones, amikacin, cytokines) that may influence therapy of MAC infection. No known therapy for MAC has been shown to prolong survival in AIDS patients, possibly because of the high organism load that exists once patients become symptomatic. Research is needed to find improved methods for earlier detection of MAC infection, determine optimal dosage regimens of current antimycobacterial agents, develop better antimycobacterial drug-delivery systems (e.g., liposomes), and discover new antimicrobials with better activity against MAC and methods of immune modulation that will overcome immune system defects.