Elvitegravir: a once-daily, boosted, HIV-1 integrase inhibitor

Abstract

The development of HIV-1 integrase strand transfer inhibitors (INSTIs) has been a major therapeutic breakthrough in the management of HIV-1 infection. The first HIV-1 integrase inhibitor, raltegravir, was licensed in 2007 and was subsequently approved for use in treatment-naive patients. Since then, newer members of the INSTI class have been developed, including elvitegravir (EVG), which is in advanced clinical development and is being developed for use in both treatment-naive and treatment-experienced patients. EVG utilizes pharmacokinetic boosting to achieve adequate serum levels with once-daily dosing. Boosting agents with which it is being studied include ritonavir and cobicistat. In addition, EVG is being studied as a once-daily INSTI in a coformulated fixed-dose combination pill with the agents tenofovir disoproxil fumarate, emtricitabine and cobicistat (QUAD pill), which has the additional potential benefit of convenient once-daily dosing. The in vitro activity, pharmacokinetic and pharmacodynamic properties, results of Phase I–III clinical trials, resistance profile and drug–drug interactions of EVG will be reviewed in this article.

Keywords::

• cobicistat
• elvitegravir
• HIV-1 integrase
• integrase drug interactions
• integrase inhibitor
• integrase pharmacokinetics
• integrase resistance

Financial & competing interests disclosure

The author has received grant support from Gilead Sciences. The author has 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.

No writing assistance was utilized in the production of this manuscript.

Notes

^†Most common secondary pathway in RAL failure with G140S leads to >1000-fold increased RAL resistance and EVG cross-resistance.

^‡Usually with N155H.

^§Usually with Y143H.

^¶Usually with Q148H/R.

^#In the study GS-183-0105, E92Q was the most common pathway associated with virologic failure, followed by N155H, Q148R/K, T66I/A/K and E138K.

^††Usually with E92Q.

^‡‡Usually with T66I.

EVG: Elvitegravir; RAL: Raltegravir.