The tolerability and pharmacokinetics of N-butyl-deoxynojirimycin in patients with advanced HIV disease (ACTG 100)

Twenty-nine patients were enrolled in a phase I dose-escalating tolerance trial of N-butyl-deoxynojirimycin, an α-glucosidase I inhibitor that inhibits human immunodeficiency virus (HIV)-1 replication by altering glycosylation of gp120. Dosing was begun at 8 mg/kg/day and subsequent doses were 16, 32, 48, and 64 mg/kg/day. The maximum tolerated dose was not achieved because of slow accrual and because the study was stopped after the finding of cataracts in initial long-range rat toxicology studies. These cataracts were later shown to be transient and not found in other animals. The most common side effects were gastrointestinal, with diarrhea and flatulence occurring in most subjects, which seemed to partially improve on a modified diet that excluded complex carbohydrates. Grade III elevations in liver function tests were seen in two patients, Grade III leukopenia and neutropenia were seen in seven patients, but were only severe enough in two to require discontinuation. No significant trends in CD4 cell counts or HIV- 1 p24 levels were noted.