Safety profile of didanosine among patients with advanced HIV disease who 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 didanosine (Videx; ddI) within the Canadian Open Treatment Program. Symptomatic HIV+ subjects with AIDS or ARC or CD4 <200/mm3 were eligible to receive didanosine if they were either (a) intolerant to zidovudine (Retrovir, ZDV) or (b) deteriorating despite ZDV therapy. The dose of didanosine (powder formulation) was based on body weight as follows: ≥75 kg, 375 mg b.i.d.; 50–74 kg, 250 mg b.i.d.; 35–49 kg, 167 mg b.i.d. Participants were monitored with physical examinations and prespecified laboratory studies by their treating physicians on a monthly basis. Follow-up data were collected in a central database through five regional coordinators. A total of 168 physicians across Canada participated in the program, and 825 subjects who started didanosine after July 1, 1990, were included in the analysis. Of these, 97% were male, 88% homosexual, and 59% had a prior diagnosis of AIDS. Reasons for enrolling was ZDV intolerance in 39%, failure in 25%, both in 32%, and other in 4%. Data were prospectively collected until July 31, 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 occurred within a month after the last dose of didanosine. Causes of death included AIDS-related unspecified causes (13 patients), MAC (11), wasting (7), AIDS-related CNS involvement other than OI's (7), Kaposi's sarcoma (7), Pneumocystis carinii pneumonia (6), sudden death, including suicides and accidents (6), lymphoma (5), toxoplasmosis (4), cryptococcosis (4), cytomegalovirus (3), unspecified causes (2), tuberculosis (1), PML (1), and disseminated histoplasmosis (1). Didanosine was discontinued in 140 (17%) subjects during the study period due to adverse events. The most common severe adverse events were diarrhea (16 patients), nausea and vomiting (11), peripheral neuropathy (7), and pancreatitis (6). We conclude that didanosine has a favorable safety profile, even among individuals with advanced HIV disease who have failed or are no longer tolerant of ZDV therapy.