title: Investigational protease inhibitors as antiretroviral therapies.
abstract: BACKGROUND
  Highly Active Antiretroviral Therapy (HAART) has tremendously improved the life expectancy of the HIV-infected population over the past three decades. Protease inhibitors have been one of the major classes of drugs in HAART regimens that are effective in treating HIV. However, the emergence of resistance and cross-resistance against protease inhibitors encourages researchers to develop new PIs with broad-spectrum activity, as well as novel means of enhancing the efficacy of existing PIs.
  
  
  METHODS
  In this article we discuss recent advances in HIV protease inhibitor (PI) development, focusing on both investigational and experimental agents. We also include a section on pharmacokinetic booster drugs for improved bioavailability of protease inhibitors. Further, we discuss novel drug delivery systems using a variety of nanocarriers for the delivery of PIs across the blood-brain barrier to treat the HIV in the brain.
  
  
  CONCLUSIONS
  We discuss our opinion on the promises and challenges on the development of novel investigational and experimental PIs that are less toxic and more effective in combating drug-resistance. Further, we discuss the future of novel nanocarriers that have been developed to deliver PIs to the brain cells. Although these are promising findings, many challenges need to be overcome prior to making them a viable option.
authors.affiliation: a Pharmaceutical Sciences , University of Tennessee Health Science Center , Memphis , TN , USA.
authors.forename: Narasimha M
authors.initials: NM
authors.lastname: Midde
authors.affiliation: a Pharmaceutical Sciences , University of Tennessee Health Science Center , Memphis , TN , USA.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Patters
authors.affiliation: b Pharmaceutical Science , College of Pharmacy, University of Findlay , Findlay , OH , USA.
authors.forename: Pss
authors.initials: P
authors.lastname: Rao
authors.affiliation: c Clinical Pharmacy , University of Tennessee Health Science Center , Memphis , TN , USA.
authors.forename: Theodore J
authors.initials: TJ
authors.lastname: Cory
authors.affiliation: a Pharmaceutical Sciences , University of Tennessee Health Science Center , Memphis , TN , USA.
authors.forename: Santosh
authors.initials: S
authors.lastname: Kumar
mesh_terms: D000818:Animals; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D001682:Biological Availability; D001812:Blood-Brain Barrier / Q000378:metabolism; D016503:Drug Delivery Systems; D015195:Drug Design; D024882:Drug Resistance, Viral; D015507:Drugs, Investigational / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D015658:HIV Infections / Q000188:drug therapy* / Q000201:enzymology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans
chemical_list: D015507:Drugs, Investigational; D017320:HIV Protease Inhibitors
keywords: HIV; Protease inhibitors; antiretroviral therapy; drug delivery; nanocarriers; pharmacoenhancers