TREATMENT WITH LETRAZURIL OF REFRACTORY CRYPTOSPORIDIAL DIARRHEA COMPLICATING AIDS

Thirty-five AIDS patients (mean CD4 count 44 x 10(6)/L) with chronic c ryptosporidiosis were treated with letrazuril at an initial oral daily dose of 50 mg in an open-label Phase I prospective trial. Treatment w as continued for greater than or equal to 10 days and for as long as t here was a response, The majority of subjects (91%), had previously fa iled paromomycin treatment. At baseline, 74% of patients had moderate (five to nine bowel movements per day) to severe (>10 bowel movements per day) diarrhea. Twenty-three subjects (66%) had a clinical response within a mean of 1.7 weeks of treatment initiation. Twenty-two patien ts had a partial response (>50% reduction in bowel movements per day f or greater than or equal to 1 week), one patient had a complete respon se (two or fewer bowel movements per day). Of the responders, 15 (65%) had a clinical relapse with worsening diarrhea at an average of 1.2 m onths following initiation of letrazuril. The other eight (35%) have h ad symptom control for an average of 2.9 months from initiation of let razuril to the latest follow-up. Microbiologic eradication was demonst rated in 10 (40%) of 25 patients with follow-up stool examinations. Se ven patients (20%) experienced a rash, all within 1 week of starting t he drug, and resolved in ail patients when the drug was discontinued. In conclusion, severely immunocompromised AIDS patients with refractor y cryptosporidiosis may show a modest, short-lived response to letrazu ril. Microbiologic response is variable and relapse high. Rash is a ma jor limiting side effect of the drug.