Antiretroviral therapy: current drugs

Abstract

The rapid advances in drug discovery and the development of antiretroviral therapy is unprecedented in the history of modern medicine. The administration of chronic combination antiretroviral therapy targeting different stages of the human immunodeficiency virus' replicative life cycle allows for durable and maximal suppression of plasma viremia. This suppression has resulted in dramatic improvement of patient survival. This article reviews the history of antiretroviral drug development and discusses the clinical pharmacology, efficacy, and toxicities of the antiretroviral agents most commonly used in clinical practice to date.

Keywords: Antiretroviral therapy; CCR5 antagonist; Fusion inhibitor; HIV; Integrase strand transfer inhibitors; Non-nucleoside reverse transcriptase inhibitors; Nucleoside/nucleotide reverse transcriptase inhibitors; Protease inhibitors.

Published by Elsevier Inc.

Figures

Figure 1. HIV Replicative Life Cycle

Cell Entry –The first step of cell entry is the attachment of the HIV envelope glycoprotein gp120 onto human chemokine receptors (CCR5 or CXCR4) on the CD4 cell surface. After the initial attachment, the next step requires fusion of the viral and cell membranes, allowing the viral proteins to enter into the cytoplasm. Reverse Transcription – After cell entry as HIV is a retrovirus, the virus’s RNA template transcribes into a double-stranded viral DNA in the presence of the enzyme reverse transcriptase. Integration – The viral double-stranded DNA produced after reverse transcription is then transported into the cellular nucleus. In the presence of the integrase enzyme, a multi-step process allows the integration of viral DNA into host genome, and ultimately formation of proviruses. Formation of Infectious Virons by HIV Proteases – After successful integration of viral DNA into the host genome and formation of proviral proteins, the next step of the HIV-1 life cycle is the cleavage of these polyproteins and formation of infectious virions. The viral enzyme protease is the key element for this process.