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Twice-Weekly Maintenance Therapy with Sulfadiazine-Pyrimethamine To Prevent Recurrent Toxoplasmic Encephalitis in Patients with AIDS

Daniel Podzamczer; Jose M. Miro; Ferran Bolao; Jose M. Gatell; Jaime Cosin; Gillem Sirera; Pere Domingo; Fernando Laguna; Juan Santamaria; Jose Verdejo, The Spanish Toxoplasmosis Study Group.
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From Ciutat Sanitaria de Bellvitge, Hospital Clnic, and Hospital Sant Pau, Barcelona, Spain. Hospital Germans Tras, Badalona, Spain. Hospital de Cruces, Bilbao, Spain. Hospital Princesa, Instituto Carlos III, and Hospital Gregorio Maranon, Madrid, Spain. For a listing of members of the Spanish Toxoplasmosis Study Group see end of text. Requests for Reprints: Daniel Podzamczer, MD, Infectious Disease Service, Cuitat Sanitaria de Bellvitge, c/Feixa Llarga s/n. L'Hospitalet, 08907 Barcelona, Spain. Acknowledgments: The authors thank Dr. Esteban Ribera, Infectious Disease Unit, Hospital Vall D'Hebro, Barcelona, and Dr. Hernando Knobel, Infectious Disease Unit, Hospital del Mar, Barcelona, for their collaboration in the evaluation of patients suspected to have toxoplasmic encephalitis; and Dr. Francisco Gudiol for his helpful review of the manuscript. Grant Support: In part by a grant from the Fondo de Investigacion de la Seguridad Social (FISS 92/1290).


Copyright ©2004 by the American College of Physicians


Ann Intern Med. 1995;123(3):175-180. doi:10.7326/0003-4819-123-3-199508010-00003
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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 than 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.

Figures

Grahic Jump Location
Figure 1.
Kaplan-Meier plots of the time to relapse of toxoplasmic encephalitis.

The line with triangles denotes the twice-weekly regimen; the line with circles denotes the daily regimen. The estimated percentages of relapse after 12 months were 30% in the group receiving the twice-weekly regimen and 6% in the group receiving the daily regimen.

Grahic Jump Location
Grahic Jump Location
Figure 2.
Kaplan-Meier plots of the time to death.

The line with triangles denotes the twice-weekly regimen; the line with circles denotes the daily regimen. Median survival was 11.9 months in the group receiving the twice-weekly regimen and 15.2 months in the group receiving the daily regimen.

Grahic Jump Location

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