PROPHYLAXIS AGAINST DISSEMINATED MYCOBACTERIUM-AVIUM COMPLEX WITH WEEKLY AZITHROMYCIN, DAILY RIFABUTIN, OR BOTH

Background Azithromycin is active in treating Mycobacterium avium comp lex disease, but it has not been evaluated as primary prophylaxis in p atients with human immunodeficiency virus (HIV) infection. Because the drug is concentrated in macrophages and has a long half-life in tissu e, there is a rationale for once-weekly dosing. Methods We compared th ree prophylactic regimens in a multicenter, double-blind, randomized t rial involving 693 HIV-infected patients with fewer than 100 CD4 cells per cubic millimeter. The patients were assigned to receive rifabutin (300 mg daily), azithromycin (1200 mg weekly), or both drugs. They we re monitored monthly with blood cultures for M. avium complex. Results In an intention-to-treat analysis, the incidence of disseminated M. a vium complex infection at one year was 15.3 percent with rifabutin, 7. 6 percent with azithromycin, and 2.8 percent with both drugs. The risk of the infection in the azithromycin group was half that in the rifab utin group (hazard ratio, 0.53; P=0.008). The risk was even lower when two-drug prophylaxis was compared with rifabutin alone (hazard ratio, 0.28; P<0.001) or azithromycin alone (hazard ratio, 0.53; P=0.03). Am ong the patients in whom azithromycin prophylaxis was not successful, 11 percent of M. avium complex isolates were resistant to azithromycin . Dose-limiting toxic effects were more common with the two-drug combi nation than with azithromycin alone (hazard ratio, 1.67; P=0.03). Surv ival was similar in all three groups. Conclusions For protection again st disseminated M. avium complex infection, once-weekly azithromycin i s more effective than daily rifabutin and infrequently selects for res istant isolates. Rifabutin plus azithromycin is even more effective bu t is not as well tolerated. (C) 1996, Massachusetts Medical Society.