Chapter 1

Introduction

Sarah Nanzigu, Francis Xavier Kasujja and Immaculate Nankya

Abstract

Over thirty antiretroviral agents have been developed since the beginning of the fight against the human immunodeficiency virus (HIV). This breakthrough was fostered by the enormous leaps made in understanding viral replication, a cycle that begins with the interaction between the virus and the host cell, usually a CD4-bearing T-lymphocyte. This results into the fusion of the viral membrane with the cellular plasma membrane and the transfer of viral material, including RNA, into the cytoplasm of the host cell. Then, using viral DNA-dependent RNA reverse transcriptase, viral DNA is formed from RNA. Viral DNA is soon translocated to the host cell nucleus where it is integrated into the host DNA in a reaction catalyzed by integrase enzyme. The proviral DNA formed at this stage is used to produce immature viral polypeptides that are eventually cleaved and packaged into mature virions by protease enzyme. Drugs have been developed that target each of these steps; they include entry inhibitors, reverse transcriptase inhibitors, integrase inhibitors, and protease inhibitors. The reverse transcriptase inhibitor, Zidovudine, a nucleoside analogue, was the first antiretroviral agent to be approved in 1987. It was followed by many other nucleotide, nucleoside and non-nucleoside reverse transcriptase inhibitors, and eventually, by protease inhibitors, integrase inhibitors and entry inhibitors. Other viral targets are still under research.

Total Pages: 3-22 (20)

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