Antiretroviral Drugs Development; Past, Present and Future

Abstract

Thirty years after the discovery of human immunodeficiency virus (HIV), more than 29 antiretroviral have been introduced. HIV at present can be managed though; it comes with consequences such as toxicity due to long term use of antiretroviral, development of resistance by HIV-1 strains and other viral or bacterial infections associated with it. Issues such as latency, socio-economic problem in the developing world has been of considerable concern. The benefits of highly active antiretroviral therapy (HAART) in the developed countries far outweighed those in the underdeveloped nations. HIV belongs to the genus Lentivirus and family Retroviridae, possess a diploid RNA and a cone shaped capsid core particles. The virus consists of major and minor structural and nonstructural proteins that perform different roles in the virus life cycle. In this review we seek to give a comprehensive account of the past, present and future directions in the development of antiretroviral drug. There are five classes of antiretroviral inhibitors which target HIV-1’s reverse transcriptase, protease, integrase, envelope fusion and co-receptor binding thereby disrupting virus replicative cycle. Strategies have emerged on how to better manage HIV patients such as simplification of drugs, complete HAART withdrawal, use of microbicides, targeted PrEP (pre-exposure prophylaxis), and vaccine development. There are several host (example; CRIM-1) proteins and virus (example; Rev and Tat) proteins that remain unexplored and could serve as potential druggable targets, thus the need for further research in this direction.