1st International Workshop on HIV Drug Resistance & Treatment Strategies 25-28 June 1997, St. Petersburg, Florida, USA

PHENOTYPIC CHANGES IN VIRAL ISOLATES TREATED WITH DELAVIRDINE TABLETS PLUS ZIDOVUDINE OR ZIDOVUDINE ALONE

Antiviral Therapy 1997;2 (Suppl 5):26 (abstract no. 41)

LK Wathen, WW Freimuth, SR Cox, CA Greenwald, CL Daenzer, Y Wang, JM Mahrer and the Delavirdine Team
Pharmacia & Upjohn, 7000 Portage Road, Kalamazoo, Michigan, USA

In order to evaluate the phenotypic changes in viral isolates from a Phase III blinded study comparing delavirdine plus zidovudine with zidovudine alone, more than 700 HIV-1-infected asymptomatic or symptomatic individuals >13 years of age with 200-500 CD4+ cells/mm³ and ≤6 months prior zidovudine experience were enrolled.

The participants were randomized to one of four treatment arms: delavirdine (200, 300 or 400 mg three times daily) plus zidovudine or zidovudine plus placebo. A random 42% of the patients were evaluated for viral phenotypic changes using standard drug susceptibility assays.

The viral burden and immunological data from this study demonstrated a significant and sustained reduction in HIV-1 RNA for up to 52 weeks and a prolonged increase in CD4+ counts in the delavirdine 400 mg plus zidovudine group. After 52 weeks on therapy, 87.5% and 50% of the isolates from patients continuing on the 400 or 300 mg delavirdine plus zidovudine treatment, respectively remained susceptible to the median trough concentration of drug for the 400 mg dose group (10.6 µM). In addition, only 12.5% and 25% of the isolates from patients on the 400 and 300 mg combination regimens became insensitive (>0.2 µM) to zidovudine, while 43% of the isolates from the monotherapy patients were resistant after 52 weeks of therapy.

These data establish that the 400 mg three times daily regimen of delavirdine tablets with zidovudine were effective in maintaining a relatively low rate of both delavirdine and zidovudine resistance. They also demonstrated that 400 mg three times daily was more effective in maintaining phenotypic susceptibility to delavirdine and zidovudine than the 300 mg dosage.

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1997-06-25
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