title: A multicentre, randomized, double-blind, placebo-controlled trial of primary cryptococcal meningitis prophylaxis in HIV-infected patients with severe immune deficiency.
abstract: OBJECTIVE
  To assess the efficacy and survival benefit of low-dose fluconazole (400 mg weekly) for primary prophylaxis for cryptococcal meningitis in patients with advanced HIV infection.
  
  
  METHODS
  A prospective multicentre, randomized, double-blind, placebo-controlled study was carried out in HIV-infected patients with CD4 counts <100 cells/microL.
  
  
  RESULTS
  Of 90 patients enrolled, 44 received fluconazole and 46 received placebo. The baseline characteristics were similar in the two groups. On an intent-to-treat basis, 10 cases of cryptococcal meningitis developed, three (6.8%) in the fluconazole group and seven (15.2%) in the placebo group. Patients in the placebo group were more likely to develop cryptococcal meningitis than those in the fluconazole group [hazard ratio=2.23; 95% confidence interval (CI): 0.58-8.63; P=0.245]. The survival benefit of fluconazole was greater than that of the placebo. The number of deaths per 10 000 person-days was 2.7 for the fluconazole group (2/7342) and 11.7 for the placebo group (9/7713) (rate difference=9; 95% CI: 0.4-17.5; P=0.046). Based on survival analysis, patients in the placebo group were 4.3 times more likely to die than those in the fluconazole group (95% CI: 0.9-19.8; P=0.065).
  
  
  CONCLUSIONS
  Fluconazole 400 mg once weekly for primary prophylaxis for cryptococcal meningitis in Thailand should be considered in HIV-infected patients, as our study suggested a survival benefit. However, a larger study should be conducted to confirm our findings.
authors.affiliation: Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. ploencha@kku.ac.th
authors.forename: P
authors.initials: P
authors.lastname: Chetchotisakd
authors.forename: S
authors.initials: S
authors.lastname: Sungkanuparph
authors.forename: B
authors.initials: B
authors.lastname: Thinkhamrop
authors.forename: P
authors.initials: P
authors.lastname: Mootsikapun
authors.forename: P
authors.initials: P
authors.lastname: Boonyaprawit
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D015725:Fluconazole / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D016919:Meningitis, Cryptococcal / Q000517:prevention & control*; D008875:Middle Aged; D011446:Prospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D015725:Fluconazole