Prophylaxis against disseminated Mycobacterium avium complex with weekly azithromycin, daily rifabutin, or both. California Collaborative Treatment Group

N Engl J Med. 1996 Aug 8;335(6):392-8. doi: 10.1056/NEJM199608083350604.


Background: Azithromycin is active in treating Mycobacterium avium complex disease, but it has not been evaluated as primary prophylaxis in patients with human immunodeficiency virus (HIV) infection. Because the drug is concentrated in macrophages and has a long half-life in tissue, there is a rationale for once-weekly dosing.

Methods: We compared three prophylactic regimens in a multicenter, double-blind, randomized trial 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 were monitored monthly with blood cultures for M. avium complex.

Results: In an intention-to-treat analysis, the incidence of disseminated M. avium 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 rifabutin 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). Among 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 combination than with azithromycin alone (hazard ratio, 1.67; P=0.03). Survival was similar in all three groups.

Conclusions: For protection against disseminated M. avium complex infection, once-weekly azithromycin is more effective than daily rifabutin and infrequently selects for resistant isolates. Rifabutin plus azithromycin is even more effective but is not as well tolerated.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS-Related Opportunistic Infections / microbiology
  • AIDS-Related Opportunistic Infections / prevention & control*
  • Adult
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / therapeutic use*
  • Antibiotics, Antitubercular / administration & dosage
  • Antibiotics, Antitubercular / adverse effects
  • Antibiotics, Antitubercular / therapeutic use*
  • Azithromycin / administration & dosage
  • Azithromycin / adverse effects
  • Azithromycin / therapeutic use*
  • Double-Blind Method
  • Drug Resistance, Microbial
  • Drug Therapy, Combination
  • Female
  • HIV Infections / complications*
  • Humans
  • Male
  • Mycobacterium avium Complex / drug effects
  • Mycobacterium avium Complex / isolation & purification
  • Mycobacterium avium-intracellulare Infection / microbiology
  • Mycobacterium avium-intracellulare Infection / prevention & control*
  • Rifabutin / administration & dosage
  • Rifabutin / adverse effects
  • Rifabutin / therapeutic use*


  • Anti-Bacterial Agents
  • Antibiotics, Antitubercular
  • Rifabutin
  • Azithromycin