Elvitegravir for the treatment of HIV infection.

摘要

Advances in antiretroviral treatment have transformed HIV-1 infection from a deadly disease to a chronic one. Novel antiretroviral drugs have been approved for clinical use. In order to achieve long-term suppression of viremia, patients have to commit and take these drugs, or others approved in the future, for the rest of their lives. However, the emergence of multidrug-resistant mutants, along with the side effects of them, often results in the failure of therapy, so better treatment options are needed. Elvitegravir is a potent HIV integrase inhibitor with antiviral activity against wild-type and drug-resistant strains of HIV. In addition, elvitegravir can also inhibit the replication of several retroviruses and lentiviruses. Elvitegravir undergoes extensive primary metabolism by hepatic and intestinal cytochrome P450 3A (CYP3A) and secondary metabolism by UDP-glucuronosyltransferase 1-1 and 1-3 (UGT1A1/3). Although boosting it with a strong CYP3A inhibitor such as ritonavir substantially increases its plasma exposure and prolongs its elimination half-life, other combinations or even monotherapy could also be considered. Ritonavir-boosted elvitegravir requires once-daily administration of a low dose. As a stand-alone agent, elvitegravir will require twice-daily dosing to achieve effective viral reductions.