title: Survival analysis of two controlled trials of rifabutin prophylaxis against Mycobacterium avium complex in AIDS.
abstract: OBJECTIVE
  Rifabutin prophylaxis has been shown to significantly decrease the incidence of Mycobacterium avium complex (MAC) bacteremia in two randomized controlled clinical trials, but a survival benefit has not been observed. An analysis of complete follow-up of these patients through August 1992 was performed to assess subsequent survival, because although follow-up in the previous trials was limited at the time of initial analysis, the analysis did suggest that a survival benefit might be emerging.
  
  
  METHODS
  Data from 1146 AIDS patients with CD4+ counts < or = 200 x 10(6)/l enrolled at 73 US and Canadian sites in two clinical trials of MAC prophylaxis were analyzed using Cox proportional hazards analysis with rifabutin use modeled as a time-dependent covariate, taking into account the initial randomized double-blind phase of the trials and the subsequent open-label phase of follow-up of those patients. Survival from date of enrollment was analyzed. Other covariates adjusted for in the analysis were CD4+ lymphocytes count, Karnofsky performance score and hospitalization for opportunistic complications of AIDS.
  
  
  RESULTS
  Patients who received open-label rifabutin may have had a better prognosis than those who did not, based on Karnofsky score and occurrence of opportunistic disease. Adjusting for these variables and for use of rifabutin as time-dependent covariates, the relative hazard (RH) of dying while receiving rifabutin prophylaxis was 0.74 for the entire cohort [95% confidence interval (CI), 0.60-0.91; P < 0.004]. For patients with an enrollment CD4+ count < or = 50 x 10(6)/l (n = 655), the RH was 0.75 (95% CI, 0.58-0.98), and for patients with an enrollment CD4+ count of > 50 x 10(6)/l (n = 491), the RH was 0.69 (95% CI, 0.49-0.99).
  
  
  CONCLUSIONS
  An analysis of the combined double-blind and open-label follow-up of two clinical trials of rifabutin prophylaxis for MAC supports the suggestion of the double-blind study that rifabutin improves survival of AIDS patients.
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Moore
authors.forename: R E
authors.initials: RE
authors.lastname: Chaisson
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000517:prevention & control; D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000401:mortality*; D000328:Adult; D000904:Antibiotics, Antitubercular / Q000627:therapeutic use*; D016470:Bacteremia / Q000150:complications / Q000401:mortality / Q000517:prevention & control; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017567:Karnofsky Performance Status; D008297:Male; D008875:Middle Aged; D015269:Mycobacterium avium Complex / Q000187:drug effects*; D016016:Proportional Hazards Models; D017828:Rifabutin / Q000627:therapeutic use*; D016019:Survival Analysis; D014376:Tuberculosis / Q000150:complications / Q000401:mortality / Q000517:prevention & control*
chemical_list: D000904:Antibiotics, Antitubercular; D017828:Rifabutin