Shafran SD, Singer J, Zarowny DP, Phillips P, Salit I, Walmsley S, Fong I, Gill J; International Conference on AIDS.

Int Conf AIDS. 1996 Jul 7-12; 11: 28 (abstract no. We.B.423).

University of Alberta, Edmonton, AB, Canada. Fax: 403-492-7137.

Objective: To compare the efficacy of two oral multidrug regimens for the treatment of Mycobacterium avium complex (MAC) bacteremia in adults with AIDS. Methods: 229 patients were randomized to either rifampin 600 mg once daily, ethambutol 15 mg/kg daily, clofazimine 100 mg once daily and ciprofloxacin 750 mg twice daily (4-drug arm) or rifabutin 600 mg once daily, ethambutol 15 mg/kg daily and clarithromycin 1000 mg twice daily (3-drug arm). The rifabutin dose was halved to 300 mg once daily after 125 patients were randomized because 24 of 62 patients on the 3-drug arm developed uveitis compared with 0 of 63 on the 4-drug arm. Blood cultures were performed at enrollment and weeks 2, 4, 8, 12, and 16, after which patients could continue assigned therapy for life. The primary endpoint was blood culture sterilization and the main secondary endpoints were survival and symptoms. Results: Of the 229 patients randomized, 4 were ineligible, 4 had non-MAC mycobacteremia and 34 had negative baseline blood cultures at the central laboratory, resulting in 187 evaluable patients. Blood culture sterilization occurred more frequently in the 3-drug arm (69% vs 29%, P is less than 0.001) including the subset of patients who received assigned therapy for at least 4 weeks (78% vs 40%, P is less than 0.001). Blood culture sterilization was more rapid with the 3-drug regimen with 87% of all sterilizations occurring by week 4 compared with 54% in the 4-drug arm (P is less than 0.001). Within the 3-drug arm, the proportion of patients achieving blood culture sterilization was greater with the 600 mg rifabutin dose (P=0.025), but the 300 mg rifabutin dose was still more effective than the 4-drug arm (P is less than 0.05). The only relapse within 16 weeks occurred in the 4-drug arm. The median survival times were 8.6 and 5.2 months in the 3- and 4-drug arms, respectively (P is less than 0.001). The median Karnofsky score which was equivalent at baseline was higher in the 3-drug arm at all assessments from weeks 2 to 16 (P is less than 0.05). Three cases of uveitis occurred in patients receiving 300 mg rifabutin, an incidence much lower than that with the 600 mg dose (P is less than 0.001). These three cases occurred later into treatment and were milder than those noted with the 600 mg dose. Conclusions: Compared with the 4-drug regimen of rifampin, ethambutol, clofazimine and ciprofloxacin, the 3-drug regimen of rifabutin, ethambutol and clarithromycin results in more frequent and more rapid clearance of MAC from the blood of AIDS patients and is associated with improved survival, better Karnofsky performance and a very low relapse rate within 16 weeks.

Publication Types:

• Meeting Abstracts

Keywords:

• Acquired Immunodeficiency Syndrome
• Adult
• Ciprofloxacin
• Clarithromycin
• Clofazimine
• Diterpenes
• Ethambutol
• Humans
• Mycobacterium avium Complex
• Mycobacterium avium-intracellulare Infection
• Rifabutin
• Rifampin
• Uveitis
• trans-crotonin

Other ID:

• 96923221

UI: 102219120

From Meeting Abstracts