The preclinical discovery and development of dolutegravir for the treatment of HIV

Abstract

Introduction: Integration of the viral genome into the host cell chromatin is a central step in the replication cycle of HIV. Blocking the viral integrase (IN) enzyme therefore provides an attractive therapeutic strategy, as evidenced by the recent clinical approval of three IN strand transfer inhibitors. Dolutegravir is a therapy that is unique in its ability to evade HIV drug resistance in treatment-naïve patients.

Areas covered: This review starts by providing a brief summary of the history of HIV-1 IN inhibitors. The authors follow this with details of the discovery and preclinical and clinical developments of dolutegravir. Finally, the authors provide details of dolutegravir’s post-launch including the launch of the combination pill of dolutegravir, abacavir and lamivudine in August 2014.

Expert opinion: The launch of raltegravir, the first IN inhibitor from Merck & Co., has created new hopes for the patient. Indeed, pharmaceutical companies have not lost courage by attempting to address the major drawbacks of this first-in-class molecule. And while the drug elvitegravir has been inserted into a four-drug combination pill providing a once-daily dosing alternative, dolutegravir has demonstrated superiority in terms of its efficacy and resistance.

Keywords:

• AIDS
• combination antiretroviral therapy
• drug resistance
• HIV integrase
• pharmacokinetics

Declaration of interest

The authors are supported by the ANRS (Agence Nationale Pour La Recherche Centre le SIDA) who sponsors Research on AIDS and Hepatitis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Notes

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