From HTS to Market: the Discovery and Development of Maraviroc, a CCR5 Antagonist for the Treatment of HIV - Accounts in Drug Discovery Case Studies in Medicinal Chemistry - page 183

CHAPTER 9
From HTS to Market: the
Discovery and Development of
Maraviroc, a CCR5 Antagonist
for the Treatment of HIV
CHRIS BARBER* AND DAVID PRYDE
Worldwide Medicinal Chemistry, Pfizer Ltd, Sandwich, Kent, CT13 9NJ,
UK
9.1 AIDS and HIV
AIDS was recognised as a disease in 1981; 1 two years later, the causative
pathogen human immunodeficiency virus 1 (HIV-1) was reported. 2,3 Since
then, this disease has become a global pandemic which is estimated to have
caused the death of 25 million people. A further 33 million individuals are
currently infected. Significant research into this disease over the past 25 years
has resulted in 25 approved drugs; 4 however, HIV can rapidly mutate to
become resistant to a single drug treatment. As a consequence, treatment is
typically a combination of at least three different drugs across a number of
classes, a regime known as HAART (highly active antiretroviral therapy).
While this has been successful in suppressing mutant viruses that may have
resistance to any one drug, such combinations can result in complex dosing
schedules and in severe side effects, which can reduce patient compliance and
allow resistant strains to emerge. One study has shown that 5-10% of patients
undergoing HAART therapy are infected with multidrug-resistant strains. 5 As