Elvitegravir: a once-daily inhibitor of HIV-1 integrase.
BACKGROUND
Elvitegravir (EVG) is a potent inhibitor of HIV-1 integrase (IN) undergoing Phase III clinical trials. It blocks the strand-transfer step in a multi-step process that allows double-stranded cDNA to be irreversibly incorporated within the host DNA. It is the second member of the HIV-1 IN inhibitor class, following raltegravir. Co-administration with a CYP3A inhibitor, such as ritonavir or cobicistat, substantially increases EVG plasma exposure and prolongs elimination half-life.


METHODS
A Medline review of Phase II and III trials involving EVG as well as a review of abstracts from major HIV and infectious disease conferences from 2010 to 2011 was conducted. EVG produces rapid and durable virologic suppression when combined with active background therapy. Trials investigating the efficacy of once-daily co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir (EVG/COBI/FTC/TDF) demonstrate a high rate of virologic suppression with fewer CNS and psychiatric adverse events compared with co-formulated efavirenz/emtricitabine/tenofovir. The resistance profile for EVG is similar to raltegravir.


CONCLUSIONS
Co-formulated EVG/COBI/FTC/TDF is an option for the treatment of antiretroviral naïve and experienced patients. Once-daily dosing offers an advantage over raltegravir, but the requirement for pharmacologic boosting increases regimen complexity. Dolutegravir in development offers a favorable resistance profile and no requirement for pharmacologic boosting.
Division of Infectious Disease and International Medicine, University of South Florida College of Medicine, 1 Tampa General Circle, Tampa, FL, USA. twills@health.usf.edu
Todd
T
Wills
Vivian
V
Vega
D019380:Anti-HIV Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D004334:Drug Administration Schedule; D004338:Drug Combinations; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D019428:HIV Integrase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D015363:Quinolones / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D004338:Drug Combinations; D019428:HIV Integrase Inhibitors; D015363:Quinolones; C509700:elvitegravir