Chapter 19 Small Molecule CCR5 and CXCR4-Based Viral Entry Inhibitors for Anti-HIV Therapy Currently in Development

Abstract

Publisher Summary This chapter discusses small molecule CCR5 and CXCR4-based viral entry inhibitors for anti-HIV therapy currently in development. CCR5 and CXCR4 antagonists represent the first potential antiretrovirals that act upon a host target and not a viral enzyme. CCR5 antagonists have demonstrated proof of concept as antivirals and long-term efficacy and safety data are now becoming available. CXCR4 antagonists are at a much earlier stage and the development of these compounds will be more complex. Tropism testing and their place in therapy are additional questions which will be clarified as better assays are developed and clinicians gain experience with these drugs. The development of entry inhibitors will provide a potent option for HIV-infected individuals at all stages of disease. It has been found that the highly active antiretroviral therapy (HAART), drug cocktails of several antiretroviral drugs, can be associated with significant side effects. Loss of efficacy of HAART due to the development of viral resistance requires close patient monitoring and continued adjustment of drug regimens in HAART. Simplified treatment regimens involving fewer pills and less-frequent administration are needed to improve patient compliance, which in turn could slow down the development of viral resistance. The chapter presents the current state of potent and highly bioavailable antiretrovirals that target cellular proteins utilized by the HIV in its replication cycle, by summarizing results of molecules currently in the clinic and by providing a snapshot of the diverse preclinical CCR5 or CXCR4 binders.