alexa Elvitegravir, an oral HIV integrase inhibitor, for the potential treatment of HIV infection.
Microbiology

Microbiology

Journal of Antivirals & Antiretrovirals

Author(s): Klibanov OM

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Abstract The treatment of HIV is often complicated by the emergence of antiretroviral (ARV) resistance, which has prompted the development of ARV drugs with novel mechanisms of action and resistance profiles. One of the newest classes of ARVs is the integrase inhibitors. These agents inhibit viral replication by preventing integration of viral DNA into the host cell. Japan Tobacco Inc and Gilead Sciences Inc are developing elvitegravir, a novel integrase inhibitor undergoing phase III clinical trials. Elvitegravir is predominantly metabolized via cytochrome P450 (CYP)3A4, along with minor pathways including glucuronidation via UGT1A1/3 and oxidative metabolism. Consequently, the coadministration of elvitegravir with the protease inhibitor ritonavir (a substantial CYP3A4 inhibitor) results in significantly enhanced bioavailability and a longer half-life than with elvitegravir alone, allowing for the once-daily dosing of elvitegravir. In vitro and clinical data suggest that elvitegravir has an overlapping resistance profile with raltegravir and with other integrase inhibitors that are in development. Data from phase I/II clinical trials have demonstrated excellent virological responses with elvitegravir, as well as minimal toxicities. At the time of publication, phase III trials to examine the efficacy and toxicity of elvitegravir were enrolling patients infected with HIV-1.
This article was published in Curr Opin Investig Drugs and referenced in Journal of Antivirals & Antiretrovirals

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