Efficacy of trimethoprim-sulfamethoxazole in the treatment of cerebral toxoplasmosis in Aids patients

Abstract

Cerebral toxoplasmosis (CT) continues to cause high morbimortality in developing
countries. The association of sulfadiazine and pyrimetamine (PS) is considered the
mainstay therapy, however, it has several disadvantages: toxicity, cost, burden of pills,
low availability and the lack of a parenteral formulation. Prospective, open, single-arm
clinical trial to evaluate the efficacy and safety of trimethoprim- sulfamethoxazole (TMPSMX) in the treatment of CT in AIDS patients. Eligible AIDS patients had presumptive
CT, were more than 18 years old, no known allergy to the study drugs, and had no
concomitant infection of the central nervous system. Patients received TMP 10 mg/kg/
day plus SMX 50 mg/kg/day BID, given orally or intravenously. Clinical and laboratory
evaluation were performed at study entry and weekly thereafter. Computed tomography
scans were performed at study entry and after 2 weeks of treatment. Clinical response was
defined as resolution of at least 50% of neurological symptoms similarly; radiological
response consisted in more than 50% decrease in number and size of initial lesions. Fortysix patients were included (23 males, median age 35) Median of CD4 cell count was 74
cells/mm³. The main symptoms were headache, hemiparesis and altered mental status.
First time of presumptive CT was reported in 33 (72%) patients and for 21% CT was the
defining aids condition. After two weeks of treatment, clinical and radiological response
occurred in 39 (85%) patients. Overall, TMP-SMX was safe, 5 (11%) patients had adverse
events; 3 (6%) patients presented a Grade 1-2 skin rash, 1(2%) patient a clinical adverse
event grade 2 and 1 (2%) patient a laboratory abnormality grade 3. During a twelve-week
follow up, a high relapse rate (22%) was observed and was associated to non-adherence,
TMP-SMX was used to treat all relapses and was effective in 90% of patients. Mortality
was 2% at 4 weeks and 9% at 12 weeks and overall mortality was 11%. In this study,
TMP-SMX was effective and well tolerated in AIDS patients with CT