Survival analysis of two controlled trials of rifabutin prophylaxis against Mycobacterium avium complex in AIDS.

Abstract

OBJECTIVES:

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: R D Moore, R E Chaisson
• Journal: AIDS (London, England) (AIDS) Vol. 9 Issue 12 Pg. 1337-42 (Dec 1995) ISSN: 0269-9370 [Print] England
• PMID: 8605053 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibiotics, Antitubercular
• Rifabutin

Topics

• AIDS-Related Opportunistic Infections (prevention & control)
• Acquired Immunodeficiency Syndrome (complications, mortality)
• Adult
• Antibiotics, Antitubercular (therapeutic use)
• Bacteremia (complications, mortality, prevention & control)
• Double-Blind Method
• Female
• Follow-Up Studies
• Humans
• Karnofsky Performance Status
• Male
• Middle Aged
• Mycobacterium avium Complex (drug effects)
• Proportional Hazards Models
• Rifabutin (therapeutic use)
• Survival Analysis
• Tuberculosis (complications, mortality, prevention & control)