Access denied? The status of co-receptor inhibition to counter HIV entry

Abstract

As resistance and long-term metabolic abnormalities hamper the efficacy of previous drugs against HIV-1, targeting of HIV co-receptors represents an exciting new frontier for antiretroviral therapeutics. CCR5 inhibitors are most likely to be the new available drugs within the class of entry inhibitors. This paper reviews the most recent clinical data available on the small-molecule compounds vicriviroc and maraviroc and on the antibodies PRO 140 and CCR5mAb004, as well as some novel genetic approaches. A thorough overview of the many challenges, past, present and future, that CCR5 inhibitors encounter during their development pathway is then presented. Possible immunologic consequences are also discussed. It could be foreseen that the benefit for HIV-infected individuals derived by the use of these potential novel drugs will outweigh the costs/risks intrinsically present in every new therapeutic approach.

Keywords::

• antiretroviral
• entry inhibitor
• CCL3
• CCL4
• CCL5
• CCR5 inhibitor
• CCR5mAb004
• CCR5-tropic
• CXCR4-tropic
• HIV infection
• maraviroc
• PRO 140
• R5
• R5X4
• vicriviroc
• viral tropism
• X4

Disclosure statement

All three authors have unrestricted educational grants from Abbott, Boehringer-Ingelheim, Bristol-Myers-Squibb, Gilead, GlaxoSmithKline, Jansen-Cilag, Merck Sharp & Dome, Pfizer, Roche, Schering-Plough, Tibotec, which contribute to supporting the continuing clinical trials that take place at the Clinic of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy.