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NLM AIDSLINE

ACTG 260: Randomized phase I/II concentration-controlled trial of the anti-HIV activity of delavirdine.




 

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.

Antiviral Agents/*ADMINISTRATION & DOSAGE Didanosine/ADMINISTRATION & DOSAGE Dose-Response Relationship, Drug Drug Therapy, Combination Female Indoles/ADMINISTRATION & DOSAGE/*THERAPEUTIC USE Male Piperazines/ADMINISTRATION & DOSAGE/*THERAPEUTIC USE Reverse Transcriptase Inhibitors/ADMINISTRATION & DOSAGE/ *THERAPEUTIC USE Zidovudine/ADMINISTRATION & DOSAGE ABSTRACT



 




Information in this article was accurate in November 30, 1996. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.