ACTG 260: a Randomized, Phase I-II, Dose-Ranging Trial of the Anti-Human Immunodeficiency Virus Activity of Delavirdine Monotherapy

Abstract

ACTG 260 was an open-label, four-arm trial designed to study the safety and anti-human immunodeficiency virus (anti-HIV) activity of delavirdine monotherapy at three ranges of concentrations in plasma compared to those of control 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 M). A total of 113 subjects were analyzed. At week 2, the mean HIV type 1 (HIV-1) RNA level declines among the subjects in the three delavirdine arms were similar (0.87, 1.08, and 1.02 log 10 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 reduction. In the subjects in the nucleoside arm, mean HIV-1 RNA level reductions at weeks 2 and 8 were 0.67 and 0.55 log 10 , respectively. Because viral suppression by delavirdine was not maintained, the trial was stopped early. Rash, which was usually self-limited, developed in 36% of subjects who received delavirdine. Delavirdine monotherapy has potent anti-HIV activity at 2 weeks, but its activity is time limited due to the rapid emergence of drug resistance.

Delavirdine Malabsorption in HIV‐Infected Subjects with Spontaneous Gastric Hypoacidity

“…The clinical significance of the pharmacokinetic differences seen between the subjects with and without gastric hypoacidity is difficult to assess because of the differences between the current clinical use of delavirdine and its use in studies evaluating pharmacokinetic‐clinical response relationships. Similar to another study of delavirdine monotherapy, 34 maculopapular rash in this study occurred more frequently in subjects with normal gastric acidity and higher delavirdine pharmacokinetic exposure, suggesting that rash may be related to delavirdine exposure. However, the delavirdine exposure in the subjects without gastric hypoacidity who had rashes was comparable to the other subjects in that particular group of subjects.…”

Adverse effects of antiretroviral therapy: focus on orofacial effects

“…Nowadays, it is mainly administered in combination with PIs or in rescue therapies, substituting a nucleoside analogue [58]. The most common side effect (seen in 30% of patients) is a pruriginous maculopapular exanthem and is usually non-severe.…”

Management of the Adverse Effects of Antiretroviral Therapy and Medication Adherence

“…The most common reported adverse effects of delavirdine are rash (18% of cases), nausea (7%), diarrhea (4%), headache (6%), fatigue (4%), and increases in transaminase levels (5%) [94,95]. Delavirdine is considered to be well tolerated.…”