title: 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. Terry Beirn Community Programs for Clinical Research on AIDS.
abstract: The optimal regimen for treatment of Mycobacterium avium complex (MAC) disease has not been established. Eighty-five AIDS patients with disseminated MAC disease were randomized to receive a three-drug regimen of clarithromycin, 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 Monitoring Board recommended discontinuation of the clarithromycin dosage comparison and continuation of the rifabutin vs. clofazimine comparison. After a mean follow-up of 4.5 months, 10 (22%) of 45 patients receiving clarithromycin at 500 mg b.i.d. had died (70 deaths per 100 person-years) compared with 17 (43%) of 40 patients receiving clarithromycin at 1,000 mg b.i.d. (158 deaths per 100 person-years) (relative risk, 2.43; 95% confidence interval, 1.11-5.34; P = .02). After 10.4 months, 20 (49%) of 41 patients receiving rifabutin had died (81 deaths per 100 person-years) compared with 23 (52%) of 44 patients receiving clofazimine (94 deaths per 100 person-years) (relative risk, 1.20; 95% confidence interval, 0.65-2.19; P = .56). Bacteriologic 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.
authors.affiliation: Denver Community Program for Clinical Research on AIDS, Colorado, USA. dcohn@dhha.org
authors.forename: D L
authors.initials: DL
authors.lastname: Cohn
authors.forename: E J
authors.initials: EJ
authors.lastname: Fisher
authors.forename: G T
authors.initials: GT
authors.lastname: Peng
authors.forename: J S
authors.initials: JS
authors.lastname: Hodges
authors.forename: J
authors.initials: J
authors.lastname: Chesnut
authors.forename: C C
authors.initials: CC
authors.lastname: Child
authors.forename: B
authors.initials: B
authors.lastname: Franchino
authors.forename: C L
authors.initials: CL
authors.lastname: Gibert
authors.forename: W
authors.initials: W
authors.lastname: El-Sadr
authors.forename: R
authors.initials: R
authors.lastname: Hafner
authors.forename: J
authors.initials: J
authors.lastname: Korvick
authors.forename: M
authors.initials: M
authors.lastname: Ropka
authors.forename: L
authors.initials: L
authors.lastname: Heifets
authors.forename: J
authors.initials: J
authors.lastname: Clotfelter
authors.forename: D
authors.initials: D
authors.lastname: Munroe
authors.forename: C R
authors.initials: CR
authors.lastname: Horsburgh
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D000328:Adult; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000904:Antibiotics, Antitubercular / Q000009:adverse effects / Q000627:therapeutic use; D017291:Clarithromycin / Q000009:adverse effects* / Q000627:therapeutic use; D002991:Clofazimine / Q000009:adverse effects / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D015269:Mycobacterium avium Complex; D015270:Mycobacterium avium-intracellulare Infection / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D010349:Patient Compliance; D011446:Prospective Studies; D017828:Rifabutin / Q000009:adverse effects / Q000627:therapeutic use; D017741:Survivors; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D000904:Antibiotics, Antitubercular; D017828:Rifabutin; D002991:Clofazimine; D017291:Clarithromycin