Document 0009
 DOCN  M95A0009
 TI    Twice-weekly maintenance therapy with sulfadiazine-pyrimethamine to
       prevent recurrent toxoplasmic encephalitis in patients with AIDS.
       Spanish Toxoplasmosis Study Group [see comments]
 DT    9510
 AU    Podzamczer D; Miro JM; Bolao F; Gatell JM; Cosin J; Sirera G; Domingo P;
       Laguna F; Santamaria J; Verdejo J; Ciutat Sanitaria de Bellvitge,
       Hospital Clinic, Barcelona,; Spain.
 SO    Ann Intern Med. 1995 Aug 1;123(3):175-80. Unique Identifier : AIDSLINE
       MED/95321510
 CM    Comment in: Ann Intern Med 1995 Aug 1;123(3):230-1
 AB    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).
       DESIGN: 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). SETTING: 8 university teaching hospitals.
       PATIENTS: 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. MEASUREMENTS: 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.
 DE    Adult  Aged  AIDS-Related Opportunistic Infections/*PREVENTION &
       CONTROL/  PARASITOLOGY  Drug Administration Schedule  Drug Therapy,
       Combination  Encephalitis/*PREVENTION & CONTROL/*PARASITOLOGY/VIROLOGY
       Female  Hospitals, University  Human  Male  Middle Age  Pneumonia,
       Pneumocystis carinii/PREVENTION & CONTROL  Pyrimethamine/*ADMINISTRATION
       & DOSAGE  Spain  Sulfadiazine/*ADMINISTRATION & DOSAGE  Support,
       Non-U.S. Gov't  Toxoplasmosis, Cerebral/*PREVENTION & CONTROL/VIROLOGY
       Treatment Outcome  CLINICAL TRIAL  JOURNAL ARTICLE  MULTICENTER STUDY
       RANDOMIZED CONTROLLED TRIAL

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).