title: Treatment of histoplasmosis with fluconazole in patients with acquired immunodeficiency syndrome. National Institute of Allergy and Infectious Diseases Acquired Immunodeficiency Syndrome Clinical Trials Group and Mycoses Study Group.
abstract: OBJECTIVE
  This study assesses the efficacy and safety of fluconazole therapy in patients with acquired immunodeficiency syndrome (AIDS) and mild to moderately severe manifestations of disseminated histoplasmosis.
  
  
  METHODS
  This was a multicenter, open-label, nonrandomized prospective trial. All patients had AIDS and disseminated histoplasmosis. Patients were treated with 1,200 mg of fluconazole given by mouth once on the first day, then 600 mg once daily for 8 weeks, and those patients who improved clinically were then assigned fluconazole maintenance therapy 200 mg once daily for at least 1 year. Interim analysis revealed a high failure rate (10 of 20, 50%), causing revision of the protocol to increase the fluconazole dose to 1,600 mg given once on the first day, then 800 mg once daily, and the duration to 12 weeks for induction therapy and then 400 mg daily for 1 year for maintenance therapy.
  
  
  RESULTS
  Thirty-six of 49 patients (74%; 95% confidence interval [CI]: 59% to 85%) with mild to moderately severe clinical manifestations who entered into the revised study responded to 800 mg of fluconazole daily for 12 weeks as induction therapy. Of the seven patients who failed induction therapy because of progression of histoplasmosis, one died of the infection. Of 36 patients who entered into the maintenance phase of the study receiving 400 mg of fluconazole daily for 1 year, 11 (30.5%) relapsed, including one who died (2.8%). Two of the 49 patients (4.1%) were removed because of grade 4 adverse events, alkaline phosphatase elevation for one and aspartate aminotransferase elevation in the other. The relapse-free rate at 1 year was 53% (95% CI: 32% to 89%), prompting closure of the study.
  
  
  CONCLUSIONS
  Fluconazole 800 mg daily is a safe and moderately effective induction therapy for mild or moderately severe disseminated histoplasmosis in patients with AIDS. On the basis of historic comparison, fluconazole 400 mg daily is less effective than itraconazole 200 to 400 mg daily or amphotericin B 50 mg given weekly as maintenance therapy to prevent relapse.
authors.affiliation: Indiana University, Indianapolis, USA.
authors.forename: J
authors.initials: J
authors.lastname: Wheat
authors.forename: S
authors.initials: S
authors.lastname: MaWhinney
authors.forename: R
authors.initials: R
authors.lastname: Hafner
authors.forename: D
authors.initials: D
authors.lastname: McKinsey
authors.forename: D
authors.initials: D
authors.lastname: Chen
authors.forename: A
authors.initials: A
authors.lastname: Korzun
authors.forename: K J
authors.initials: KJ
authors.lastname: Shakan
authors.forename: P
authors.initials: P
authors.lastname: Johnson
authors.forename: R
authors.initials: R
authors.lastname: Hamill
authors.forename: D
authors.initials: D
authors.lastname: Bamberger
authors.forename: P
authors.initials: P
authors.lastname: Pappas
authors.forename: J
authors.initials: J
authors.lastname: Stansell
authors.forename: S
authors.initials: S
authors.lastname: Koletar
authors.forename: K
authors.initials: K
authors.lastname: Squires
authors.forename: R A
authors.initials: RA
authors.lastname: Larsen
authors.forename: T
authors.initials: T
authors.lastname: Cheung
authors.forename: N
authors.initials: N
authors.lastname: Hyslop
authors.forename: K K
authors.initials: KK
authors.lastname: Lai
authors.forename: D
authors.initials: D
authors.lastname: Schneider
authors.forename: C
authors.initials: C
authors.lastname: Kauffman
authors.forename: M
authors.initials: M
authors.lastname: Saag
authors.forename: W
authors.initials: W
authors.lastname: Dismukes
authors.forename: W
authors.initials: W
authors.lastname: Powderly
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy*; D000328:Adult; D000935:Antifungal Agents / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D015725:Fluconazole / Q000627:therapeutic use*; D006660:Histoplasmosis / Q000188:drug therapy*; D006801:Humans; D008297:Male; D018579:Patient Selection; D011446:Prospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D015725:Fluconazole