title: Twice-weekly maintenance therapy with sulfadiazine-pyrimethamine to prevent recurrent toxoplasmic encephalitis in patients with AIDS. Spanish Toxoplasmosis Study Group.
abstract: OBJECTIVE
  To evaluate the efficacy of twice-weekly maintenance therapy with sulfadiazine-pyrimethamine to prevent toxoplasmic encephalitis relapse in patients with the acquired immunodeficiency syndrome (AIDS).
  
  
  METHODS
  Randomized, open, multicenter trial. Patients were randomly assigned to receive sulfadiazine (500 mg) four times per day plus pyrimethamine (25 mg) plus folinic acid (15 mg) either daily (n = 60) or twice weekly (n = 45).
  
  
  METHODS
  8 university teaching hospitals.
  
  
  METHODS
  Between February 1990 and June 1993, 105 patients with HIV infection were enrolled after each had had resolution of an acute episode of toxoplasmic encephalitis treated with sulfadiazine (1 g four times per day) plus pyrimethamine (50 mg/d) plus folinic acid (15 mg/d) for 4 to 8 weeks.
  
  
  METHODS
  Clinical and biological evaluations done every 30 to 60 days. End points were toxoplasmic encephalitis relapse, death, and interruption of therapy due to adverse reactions.
  
  
  RESULTS
  After a median follow-up period of 11 months (range, 1 to 39 months), patients receiving the twice-weekly regimen had a higher rate of relapse then patients receiving the daily regimen (19.5 compared with 4.4 per 100 patient-years; incidence rate ratio, 4.36 [95% CI, 1.05 to 25.5]; P = 0.024). The estimated cumulative percentages of relapse at 12 months were 30% and 6%, respectively (P = 0.029), with an adjusted risk ratio (adjusted for age, sex, risk behavior, previous diagnosis of AIDS, Pneumocystis carinii pneumonia prophylaxis before initial episode of toxoplasmosis, CD4 cell count, baseline number of brain lesions, radiologic sequelae, and antiretroviral therapy during follow-up) of 5.6 (CI, 1.2 to 25.6; P = 0.028). Patients receiving the twice-weekly regimen had 1.6 times (CI, 0.9 to 2.9 times; P = 0.11) the adjusted risk for death of patients receiving the daily regimen. No statistical differences were found in the patients who stopped receiving the regimens due to adverse effects. No patient developed P. carinii pneumonia during the study period, even though 17 patients (10 receiving the daily regimen and 7 receiving the twice-weekly regimen) had had an episode of P. carinii pneumonia before study entry.
  
  
  CONCLUSIONS
  At the given doses, a combination of sulfadiazine, pyrimethamine, and folinic acid was less effective when administered twice weekly than when administered daily, although the twice-weekly regimen was much more effective than historic controls.
authors.affiliation: Ciutat Sanitaria de Bellvitge, Hospital Clínic, Barcelona, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Podzamczer
authors.forename: J M
authors.initials: JM
authors.lastname: Miró
authors.forename: F
authors.initials: F
authors.lastname: Bolao
authors.forename: J M
authors.initials: JM
authors.lastname: Gatell
authors.forename: J
authors.initials: J
authors.lastname: Cosín
authors.forename: G
authors.initials: G
authors.lastname: Sirera
authors.forename: P
authors.initials: P
authors.lastname: Domingo
authors.forename: F
authors.initials: F
authors.lastname: Laguna
authors.forename: J
authors.initials: J
authors.lastname: Santamaría
authors.forename: J
authors.initials: J
authors.lastname: Verdejo
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000469:parasitology / Q000517:prevention & control*; D000328:Adult; D000368:Aged; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004660:Encephalitis / Q000469:parasitology* / Q000517:prevention & control* / Q000821:virology; D005260:Female; D006785:Hospitals, University; D006801:Humans; D008297:Male; D008875:Middle Aged; D011020:Pneumonia, Pneumocystis / Q000517:prevention & control; D011739:Pyrimethamine / Q000008:administration & dosage*; D013030:Spain; D013411:Sulfadiazine / Q000008:administration & dosage*; D016781:Toxoplasmosis, Cerebral / Q000517:prevention & control* / Q000821:virology; D016896:Treatment Outcome
chemical_list: D013411:Sulfadiazine; D011739:Pyrimethamine