Chemical Biology: Approaches to Drug Discovery and Development to Targeting Disease

Chapter 16: Human Immunodeficiency Virus (HIV)

Joseph P. Vacca

Merck Research Laboratories, West Point

The human immunodeficiency retrovirus (HIV), recognized widely as the causative agent of AIDS, was discovered over 25 years ago and is one of the most highly studied viruses of all time. In the 1980s through the mid 1990s, only a few treatment options were available and contracting this virus usually resulted in death. Since the introduction in the mid-1990s of HAART (Highly Active Anti-Retroviral Therapy), the disease has become manageable for many people who can tolerate the new drugs (1, 2). This review chapter will describe the way that the virus works and will highlight the many points of intervention and the small molecules that have been developed to stop the virus from replicating.

16.1 Introduction

HIV is now widely recognized as the causative agent of acquired immunodeficiency syndrome (AIDS), and it is now estimated that over 30 million people are infected worldwide [3]. The discovery of the virus in 1983 and the ensuing epidemic spurred on the intense study of the mechanism of viral infectivity and how it might be incapacitated [4, 5]. This resulted in an intense effort toward the discovery and development of drugs by academic and industrial laboratories, and now over 24 approved drugs are available as either single agents or fixed-dose combination products (Table 16.1) [6, 7]. The available drugs come from four different classes: entry/fusion inhibitors, reverse transcriptase ...