title: Two controlled trials of rifabutin prophylaxis against Mycobacterium avium complex infection in AIDS.
abstract: BACKGROUND
  Disseminated Mycobacterium avium complex infection eventually develops in most patients with the acquired immunodeficiency syndrome (AIDS). This infection results in substantial morbidity and reduces survival by about six months.
  
  
  METHODS
  We conducted two randomized, double-blind, multicenter trials of daily prophylactic treatment with either rifabutin (300 mg) or placebo. All the patients had AIDS and CD4 cell counts < or = 200 per cubic millimeter. The primary end point was M. avium complex bacteremia as assessed monthly by blood culture. The secondary end points were signs and symptoms associated with disseminated M. avium complex infection, adverse events, hospitalization, and survival.
  
  
  RESULTS
  In the first trial, M. avium complex bacteremia developed in 51 of 298 patients (17 percent) assigned to placebo and 24 of 292 patients (8 percent) assigned to rifabutin (P < 0.001). In the second trial, bacteremia developed in 51 of 282 patients in the placebo group (18 percent) and 24 of 274 patients in the rifabutin group (9 percent) (P = 0.002). Rifabutin significantly delayed fatigue, fever, decline in the Karnofsky performance score (by > or = 20 percent), decline in the hemoglobin level (by more than 10 percent), elevation in alkaline phosphatase, and hospitalization. The incidence of adverse events was similar with rifabutin and placebo. Overall survival did not differ significantly between the two groups, although there were fewer deaths with rifabutin (33) than with placebo (47) during the double-blind phase (P = 0.086). The distribution of minimal inhibitory concentrations of rifabutin among the isolates of M. avium complex did not differ significantly between the treatment groups.
  
  
  CONCLUSIONS
  Rifabutin, given prophylactically, reduces the frequency of disseminated M. avium complex infection in patients with AIDS and CD4 counts < or = 200 per cubic millimeter.
authors.affiliation: University of Texas Southwestern Medical Center, Dallas.
authors.forename: S D
authors.initials: SD
authors.lastname: Nightingale
authors.forename: D W
authors.initials: DW
authors.lastname: Cameron
authors.forename: F M
authors.initials: FM
authors.lastname: Gordin
authors.forename: P M
authors.initials: PM
authors.lastname: Sullam
authors.forename: D L
authors.initials: DL
authors.lastname: Cohn
authors.forename: R E
authors.initials: RE
authors.lastname: Chaisson
authors.forename: L J
authors.initials: LJ
authors.lastname: Eron
authors.forename: P D
authors.initials: PD
authors.lastname: Sparti
authors.forename: B
authors.initials: B
authors.lastname: Bihari
authors.forename: D L
authors.initials: DL
authors.lastname: Kaufman
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000382:microbiology / Q000401:mortality / Q000517:prevention & control*; D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016470:Bacteremia / Q000382:microbiology / Q000401:mortality / Q000517:prevention & control*; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D015269:Mycobacterium avium Complex; D015270:Mycobacterium avium-intracellulare Infection / Q000401:mortality / Q000517:prevention & control*; D017828:Rifabutin; D012294:Rifamycins / Q000627:therapeutic use*; D012306:Risk
chemical_list: D000900:Anti-Bacterial Agents; D012294:Rifamycins; D017828:Rifabutin