title: Dose-escalation, phase I/II study of azithromycin and pyrimethamine for the treatment of toxoplasmic encephalitis in AIDS.
abstract: OBJECTIVE
  To assess the safety, tolerance and activity of increasing doses of azithromycin in combination with pyrimethamine for the treatment of toxoplasmic encephalitis (TE) in patients with AIDS.
  
  
  METHODS
  A phase I/II dose-escalation study of oral azithromycin in combination with pyrimethamine.
  
  
  METHODS
  Eight clinical sites in the United States.
  
  
  METHODS
  Forty-two adult HIV-infected patients with confirmed or presumed acute TE.
  
  
  METHODS
  Patients were enrolled into three successive cohorts receiving azithromycin 900, 1200 and 1500 mg a day with pyrimethamine as induction therapy. The induction period was 6 weeks followed by 24 weeks of maintenance therapy.
  
  
  METHODS
  Patient response was evaluated clinically and radiologically.
  
  
  RESULTS
  Of the 30 evaluable patients, 20 (67%) responded to therapy during the induction period. Ten experienced disease progression. Of the 15 patients who received maintenance therapy, seven (47%) relapsed. Six patients discontinued treatment during the induction period as a result of reversible toxicities. Treatment-terminating adverse events occurred most frequently among the patients receiving the 1500 mg dose.
  
  
  CONCLUSIONS
  The combination of azithromycin (900-1200 mg a day) and pyrimethamine may be useful as an alternative therapy for TE among patients intolerant of sulfonamides and clindamycin, but maintenance therapy with this combination was associated with a high relapse rate. The combination was safe, but low-grade adverse events were common.
authors.affiliation: Department of Medicine, Mt Sinai Medical Center, New York, NY 10029, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Jacobson
authors.forename: R
authors.initials: R
authors.lastname: Hafner
authors.forename: J
authors.initials: J
authors.lastname: Remington
authors.forename: C
authors.initials: C
authors.lastname: Farthing
authors.forename: J
authors.initials: J
authors.lastname: Holden-Wiltse
authors.forename: E M
authors.initials: EM
authors.lastname: Bosler
authors.forename: C
authors.initials: C
authors.lastname: Harris
authors.forename: D T
authors.initials: DT
authors.lastname: Jayaweera
authors.forename: C
authors.initials: C
authors.lastname: Roque
authors.forename: B J
authors.initials: BJ
authors.lastname: Luft
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000000981:diagnostic imaging / Q000188:drug therapy*; D000328:Adult; D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000981:Antiprotozoal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D017963:Azithromycin / Q000009:adverse effects / Q000627:therapeutic use*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004660:Encephalitis / Q000000981:diagnostic imaging / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D011739:Pyrimethamine / Q000009:adverse effects / Q000627:therapeutic use*; D011859:Radiography; D014122:Toxoplasma; D014123:Toxoplasmosis / Q000000981:diagnostic imaging / Q000188:drug therapy*; D016896:Treatment Outcome; D014481:United States
chemical_list: D000900:Anti-Bacterial Agents; D000981:Antiprotozoal Agents; D017963:Azithromycin; D011739:Pyrimethamine