ACTG 260: a randomized, phase I-II, dose-ranging trial of the anti-human immunodeficiency virus activity of delavirdine monotherapy

ACTG 260 was an open-label, four-arm trial designed to study the safety and anti-human immunodeficiency virus (anti-HIV) activity of delavirdine monot herapy at three ranges of concentrations in plasma compared to those of con trol therapy with zidovudine or didanosine. Delavirdine doses were adjusted weekly until subjects were within their target trough concentration range (3 to 10, 11 to 30, or 31 to 50 mu M). A total of 113 subjects were analyze d. At week 2, the mean HIV type 1 (HIV 1) RNA level declines among the subj ects in the three delavirdine arms were similar (0.87, 1.08, and 1.02 log(1 0) for the low, middle, and high target arms, respectively), but by week 8, the subjects in the pooled delavirdine arms showed only a 0.10 log(10) red uction. In the subjects in the nucleoside arm, mean HIV-1 RNA level reducti ons at weeks 2 and 8 were 0.67 and 0.55 log(10), respectively. Because vira l suppression by delavirdine was not maintained, the trial was stopped earl y. Rash, which was usually self-limited, developed in 36% of subjects who r eceived delavirdine. Delavirdine monotherapy has potent anti-HIV activity a t 2 weeks, but its activity is time limited due to the rapid emergence of d rug resistance.