Novel integrase inhibitors for HIV.
BACKGROUND
Integrase inhibitors are the newest class of antiretroviral agents developed to treat HIV-1 infection. Raltegravir (RAL), the only integrase inhibitor (INI) currently approved for the treatment of HIV-infected patients, has proven to be a potent and well-tolerated antiretroviral (ARV) agent. It is currently approved and used for the treatment of both ARV-experienced and ARV-naive patients. Nevertheless, the relatively low genetic barrier for resistance of RAL encourages the search for new INIs with different mechanisms of actions and resistance profiles.


METHODS
Here we review the data available about INI that are currently being tested in clinical trials or are in preclinical development: elvitegravir (EVG), S/GSK1349572, S/GSK1265744 and LEDGINs. We focus on their clinical efficacy, pharmacokinetic, safety and resistance profiles.


RESULTS
Up-to-date overview on the currently available, clinically relevant INIs and promising preclinical inhibitors at all phases of development.


CONCLUSIONS
Integrase inhibitors represent the newest therapeutic class available to treat HIV-1 infection. There are a variety of compounds either available in the clinic (RAL), advancing to Phase III trials (EVG), or in earlier phases of development. Taken together, this class offers new treatment options for the HIV-infected individual.
Prada
Nicole
N
Aaron Diamond AIDS Research Center, 455 First Ave., 7th floor, New York, NY 10016, USA.
Markowitz
Martin
M
D002460:Cell Line; D002986:Clinical Trials as Topic; D015195:Drug Design; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D019427:HIV Integrase / Q000235:genetics; D019428:HIV Integrase Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D011760:Pyrrolidinones / Q000494:pharmacology / Q000627:therapeutic use; D000068898:Raltegravir Potassium
D019428:HIV Integrase Inhibitors; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium; D019427:HIV Integrase