Forty-three hemophiliacs with
AIDS or
ARC received a daily dose of 334 or 500 mg
didanosine (
2',3'-dideoxyinosine or ddI) orally in 2 divided doses in phase I/II, open-label clinical trial conducted in Japan. Twenty-eight patients completed 6 months of
therapy. There was an increase in circulating CD4(+) cells in 19 valuable patients from 91 +/- 25 (mean +/- SE) at entry to 131 +/- 38 at 24 weeks of
therapy P = 0.01; Wilcoxon signed rank). Fourteen of 37 patients met the criteria for CD4 rise >/= 50/mm3 rise or >/= 50% increase from entry values) for more than 4 consecutive weeks. Twenty patients were p24 positive at entry. Nine out of the 10 evaluable patients (90%) showed a decline in p24
antigen at weeks 20-24 (P = 0.02). Thirty-five patients had symptoms related to HIV-1
infection at entry. Twenty-seven patients reported improvements in constitutional symptoms during
therapy. Nine patients presented with possible
drug-related adverse effects, and
didanosine was discontinued in 6 patients (one each with
edema;
abdominal pain with
anorexia;
hematuria with
edema and
rash; sense of abdominal distension with
anorexia;
diarrhea and
abdominal pain; and irritability). One patient had a transient increase in serum
amylase level to twice the upper limit of normal, but he continued to receive the
drug. These data suggest that
didanosine was generally well tolerated in hemophiliacs with
AIDS or
ARC, and its administration correlated with improvement in constitutional symptoms and laboratory findings. The adverse effects of
didanosine seen in this population were moderate to mild, and no complications related to
hemorrhagic diathesis were observed, although the relative risk of
acute pancreatitis in this population (while not seen in the present study to date) requires more study.