Random and rational approaches to HIV drug discovery in Africa

Abstract

The development of therapeutic agents to inhibit human immunodeficiency virus (HIV) replication began soon after the isolation and identification of the virus as the causative agent of the acquired immune deficiency syndrome (AIDS). Within a short period of time thereafter, azidothymidine (AZT) was found to inhibit viral replication and became the first FDA-approved drug for the treatment of HIV/AIDS in 1987. Since then, continual and substantial progress has been made. To date, 35 drugs have been clinically approved, and with treatment, HIV infection has been transformed from a life-threatening disease with a short survival rate into a chronic manageable condition. Furthermore, several drugs are currently under investigation in various stages of clinical and preclinical development. Despite this remarkable success, there is continued global effort directed towards the design, discovery and development of novel inhibitors that may improve treatment strategies and overcome new challenges that have arisen. This chapter focuses on the discovery phase of the HIV drug discovery and development pipeline and describes the contribution and progress made by African scientists and research laboratories. Review of the period 1990 to present day reveals considerable African research describing anti-HIV inhibitors, derived from natural sources or through synthetic means, and identified through both rational and random drug discovery approaches. Several challenges facing HIV researchers on the continent disproportionately affected by HIV/AIDS are also described.