Brief Update on the Treatment of Mycobacterium avium Complex (MAC Disease)
Several recent studies have produced important information on the optimal
management of MAC disease in patients with HIV infection. Currently,
clarithromycin at a dose of 500 mg twice daily is the cornerstone of therapy,
though azithromycin at a dose of 600 mg daily may have similar activity.
Resistance rapidly develops if these drugs are used alone, and there is complete
cross-resistance with clarithromycin and azithromycin. Earlier studies of
clarithromycin suggested that doses of >1000 mg twice daily were associated
with higher mortality than a dose of 500 mg twice daily [Annals Internal
Medicine 1994;121:905]. A study performed by the Community Program for Clinical
Research on AIDS (CPCRA) evaluated the efficacy of two doses of clarithromycin
in combination regimens for disseminated MAC infections [Cohn et al., XI Int
Conf AIDS, LB065]. Patients with disseminated MAC infection were randomly
assigned to receive clarithromycin at a dose of either 500 mg BID or 1000 mg
BID, in combination with other agents. An independent data safety monitoring
board halted the study early after high mortality rates were observed in the
patients assigned to the higher dose of clarithromycin (rate: 159 deaths per 100
person years versus 70 deaths per 100 person years). The US Food and Drug
Administration had approved clarithromycin for treatment of MAC only at the 500
Clofazimine has been found in several studies to have minimal to no activity in treating MAC, and may be dangerous. The Abbott trial mentioned above found patients who received clofazimine in addition to clarithromycin and ethambutol had significantly higher mortality than patients who only received the latter two drugs. Studies by May and coworkers [XI Int Conf AIDS] and Dube and associates [3rd Nat Conf Retrovirus Opport Inf] show that clofazimine is inferior to other combinations in preventing relapse and emergence of resistance.
Based on the emerging information, treatment of MAC infection initially should be with clarithromycin 500 mg twice daily (or azithromycin 600 mg daily) plus ethambutol 15 mg/kg/daily with or without rifabutin (300-450 mg daily). In patients who may have macrolide resistant disease, the three drug combination should be used. Treatment of relapsed disease due to resistance is difficult, as there are no additional agents with proved activity. One option is to add two new agents, such as amkacin and ciprofloxacin, though the efficacy of such manuevers is unknown. Ongoing studies are looking at two- versus three-drug combinations for initial therapy, as well as several "salvage" regimens. The role of immunotherapy in treating MAC is also under investigation. The substantial progress made in the past several years has had an emormous impact on the quality of life for patients with MAC disease.
This article was provided by Johns Hopkins AIDS Service. It is a part of the publication Hopkins HIV Report.