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In Vitro Anti-HIV-1 Activity of Vicriviroc (SCH 417690) in Combination With Other Antiretroviral Drugs and Against Resistant HIV-1 Strains
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Reported by Jules Levin
ICAAC Dec 17, 2005, Wash DC
Lisa Wojcik1, Ferdous Gheyas2, Robert Ogert1, and Julie M. Strizki1 1Biological Research – Virology, 2Statistics, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
Vicriviroc is one of a new class of CCR5 antagonists that is currently being developed for HIV therapy. This compound specifically binds the viral coreceptor CCR5 and prevents infection of target cells1,2. It is anticipated that this new class of drugs will be used in combination with other approved agents as part of an effective antiretroviral regimen. Therefore, as part of the preclinical development of this compound we assessed the antiviral potency of vicriviroc with drugs from all currently approved drug classes in an in vitro infection system.
In the clinic, it is likely that CCR5 antagonists will be used in patients with preexisting drug resistance mutations to reverse transcriptase or protease inhibitors. Therefore, in this study we have also assessed the antiviral activity of vicriviroc against a panel of recombinant viruses harboring multiple mutations
associated with single or multiple drug resistance phenotypes.
Author Conclusions
- The antiviral activity of vicriviroc was enhanced when combined with drugs from all other classes of antiretrovirals suggesting additive to synergistic activity.
- No evidence for antagonism with vicriviroc was observed with any of the other drugs tested.
- Vicriviroc exhibited potent antiviral activity against recombinant viruses carrying multiple drug resistance mutations to reverse transcriptase inhibitors, protease inhibitors and the fusion inhibitor, enfuvirtide.
- These results further support the development of vicriviroc as a member of a new class of entry inhibitors to be used as part of an antiretroviral regimen to treat HIV infection.
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