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Current Opinion in HIV & AIDS:
doi: 10.1097/COH.0b013e3283567309
INTEGRASE INHIBITORS: Edited by Charles Hicks and Esteban Martinez

HIV integrase as a target for antiretroviral therapy

Hazuda, Daria J.

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Abstract

Purpose of review: Integrase strand transfer inhibitors are the most recent class of antiretroviral agents to be introduced into clinical practice. This review describes the discovery of the first inhibitors and insights into their distinct mechanism of action with potential translational implications.

Recent findings: HIV replication depends on the successful integration of the viral genetic material into the host cell chromosome. The virally encoded enzyme integrase mediates both the DNA cutting and strand transfer or DNA joining steps which are required for this process. Understanding the mechanistic aspects of integration was critical for the initial discovery of integrase strand transfer inhibitors and the advancement of clinical candidates. The recent adoption of these inhibitors into clinic practice has now proven the therapeutic utility of the class. Integrase inhibitors are characterized by a more rapid decrease in viral load in HIV-1-infected patients initiating therapy and possess prolonged window for intervention in the viral life cycle, thus offering an advantage in the setting of HIV-1 chemoprevention.

Summary: The distinct biochemical and antiviral mechanism of action of integrase strand transfer inhibitors are directly relevant to understanding the clinical properties which are characteristic of the class and their potential significance for the use of these agents in both treatment and prevention.

© 2012 Lippincott Williams & Wilkins, Inc.

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