Clarithromycin and ethambutol with or without clofazimine for the treatment of bacteremic Mycobacterium avium complex disease in patients with HIV infection.

OBJECTIVE

To compare the efficacy of two- and three-drug regimens for treating Mycobacterium avium complex (MAC) bacteremia in patients with AIDS.

DESIGN

Randomized open-label clinical trial.

SETTING

Outpatient HIV specialty centers' clinics.

PATIENTS: A total of 106 adults with AIDS and MAC bacteremia.

INTERVENTIONS: Patients were treated with clarithromycin 500 mg twice daily and ethambutol 800-1,000 mg daily and were randomized to receive clofazimine 100 mg daily or no clofazimine.

MAIN OUTCOME MEASURES: Quantitative blood MAC cultures, symptoms, adverse reactions and survival.

RESULTS

Patients randomly assigned to three drugs had significantly higher baseline colony counts of MAC in blood than patients receiving two drugs. The proportion of patients becoming culture-negative was 65% in the two-drug group and 54% in the three-drug group. The median time to negative culture was 58 days for patients in the two-drug and 63 days for the three-drug group. At the last visit during treatment, the mean reduction in colony forming units/ml of MAC in blood was 1.8 log10 for the two-drug group and 2.3 log10 for the three-drug group. Improvement in fever and night sweats was reported by 87 and 89% of the two-drug patients and 84 and 86% of the three-drug patients. During the study, 38% of two-drug patients and 61% of three-drug patients died (P = 0.032), and time to death was shorter in patients treated with three drugs (P = 0.012). In a multivariate analysis, both assignment to clofazimine and high baseline colony counts of MAC bacteremia were significantly associated with death (P < 0.05).

CONCLUSION

The addition of clofazimine to a regimen of clarithromycin and ethambutol for MAC bacteremia in AIDS patients does not contribute to clinical response and is associated with higher mortality.