A prospective randomized trial of four three-drug regimens in the treatment of disseminated Mycobacterium avium complex disease in AIDS patients: Excess mortality associated with high-dose clarithromycin

The optimal regimen for treatment of Mycobacterium avium complex (MAC) dise ase has not been established. Eighty-five AIDS patients with disseminated M AC disease were randomized to receive a three-drug regimen of clarithromyci n, rifabutin or clofazimine, and ethambutol. Two dosages of clarithromycin, 500 or 1,000 mg twice daily (b.i.d.), were compared. The Data and Safety M onitoring Board recommended discontinuation of the clarithromycin dosage co mparison and continuation of the rifabutin vs. clofazimine comparison. Afte r a mean follow-up of 4.5 months, 10 (22%) of 45 patients receiving clarith romycin at 500 mg b.i.d. had died (70 deaths per 100 person-years) compared with 17 (43%) of 30 patients receiving clarithromycin at 1,000 mg b.i.d. ( 158 deaths per 100 person-years) (relative risk, 2.43; 95% confidence inter val, 1.11-5.34; P = .02). After 10.4 months, 20 (49%) of 41 patients receiv ing rifabutin had died (81 deaths per 100 person-years) compared with 23 (5 2%) of 44 patients receiving clofazimine (94 deaths per 100 person-years) ( relative risk, 1.20; 95% confidence interval, 0.65-2.19; P = .56). Bacterio logic outcomes were similar among treatment groups. In treating MAC disease in AIDS patients, the maximum dose of clarithromycin should be 500 mg b.i. d.