translation agency

NLM AIDSLINE
ACTG 260: Randomized phase I/II concentration-controlled trial of the anti-HIV activity of delavirdine.
Para MF; Fischl M; Meehan P; Morse G; Wood K; Shafer R; Freimuth W;
November 30, 1996
3rd Conf Retro and Opportun Infect. 1996 Jan 28-Feb 1;:163. Unique

Objectives: Delavirdine, (DLV) has potent in-vitro anti-HIV activity but prior use in man has been limited to combination therapy in doses up to 1200mg/d. ACTG 260 was designed to study the safety and anti-HIV activity (as measured by HIV RNA) of DLV monotherapy (at 3 concentrations) vs. ZDV or ddI. Methods: This was a randomized, multi-center, open-label, 4-arm trial in HIV+ subjects with CD4=200-500. Half were ZDV naive. DLV dose adjustments were made weekly until subjects were within their target trough range (3-10, 11-30, 31-50micromolar). These levels were selected to meet/exceed the IC50 of DLV induced mutant isolates. This 120 patient trial was to last 24 week but was to be stopped early if 30% of subjects did not have a 0.7 log10 reduction in RNA at week 8. Findings: 59 ZDV-experienced and 56 naive subjects (84% male, 69% white) enrolled. Concentration-targeted troughs were attained in a majority of patients with DLV doses up to 2550 mg/d. 30/84 of DLV subjects developed rash, 7 were grade 3/4. The incidence of rash was related to the dosing arm. 13 DLV subjects had a grade 3/4 toxicity. Viral RNA had fallen a median of 0.87, 1.09 and 0.86 log10 at week 2 in the low, mid & high DLV arms with greater viral suppression in those ZDV naive. By week 8 however, the pooled DLV arms showed only a 0.12 log10 RNA reduction and mutant isolates with decreased DLV sensitivity were detected. In the pooled DLV arms, the median CD4 count increased by 25 at week 2 but was back to baseline by week 8. In the nucleoside arm, RNA was 0.68 log10 and 0.65 log10 lower at weeks 2 and 8. Since viral suppression by the DLV was limited at week 8, the trial stopped early with 66 subjects completing 24 weeks. 9/59 DLV subjects had greater than or equal to 0.5 log RNA reduction at last visit greater than or equal to week 16. Conclusions: DLV monotherapy appears safe with potent but time limited anti-HIV activity. Rapid access to drug and RNA levels allowed a unique study design with individualized dosing and quick assessment of study objectives.

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