SAFETY PROFILE OF DIDANOSINE AMONG PATIENTS WITH ADVANCED HIV DISEASEWHO ARE INTOLERANT TO OR DETERIORATE DESPITE ZIDOVUDINE THERAPY - RESULTS OF THE CANADIAN-OPEN-DDI-TREATMENT-PROGRAM

The aim of this study was to ascertain the safety profile of didanosin e (Videx; ddI) within the Canadian Open Treatment Program. Symptomatic HIV+ subjects with AIDS or ARC or CD4 <200/mm(3) were eligible to rec eive didanosine if they were either (a) intolerant to zidovudine (Retr ovir, ZDV) or (b) deteriorating despite ZDV therapy. The dose of didan osine (powder formulation) was based on body weight as follows: greate r than or equal to 75 kg, 375 mg b.i.d.; 50-74 kg, 250 mg b.i.d.; 35-4 9 kg, 167 mg b.i.d. Participants were monitored with physical examinat ions and prespecified laboratory studies by their treating physicians on a monthly basis. Follow-up data were collected in a central databas e through five regional coordinators. A total of 168 physicians across Canada participated in the program, and 825 subjects who started dida nosine after July 1, 1990, were included in the analysis. Of these, 97 % were male, 88% homosexual, and 59% had a prior diagnosis of AIDS. Re asons for enrolling was ZDV intolerance in 39%, failure in 25%, both i n 32%, and other in 4%. Data were prospectively collected until July 3 1, 1991. Total follow-up was 3,440 patient-months and median follow-up was 4.3 months. A total of 78 deaths were reported, 44 of which occur red within a month after the last dose of didanosine. Causes of death included AIDS-related unspecified causes (13 patients), MAC (11), wast ing (7), AIDS-related CNS involvement other than OI's (7), Kaposi's sa rcoma (7), Pneumocystis carinii pneumonia (6), sudden death, including suicides and accidents (6), lymphoma (5), toxoplasmosis (4), cryptoco ccosis (4), cytomegalovirus (3), unspecified causes (2), tuberculosis (1), PML (1), and disseminated histoplasmosis (1). Didanosine was disc ontinued in 140 (17%) subjects during the study period due to adverse events. The most common severe adverse events were diarrhea (16 patien ts), nausea and vomiting (11), peripheral neuropathy (7), and pancreat itis (6). We conclude that didanosine has a favorable safety profile, even among individuals with advanced HIV disease who have failed or ar e no longer tolerant of ZDV therapy.