title: Dolutegravir, a second-generation integrase inhibitor for the treatment of HIV-1 infection.
abstract: OBJECTIVE
  To review the pharmacology, safety, and efficacy of dolutegravir, an integrase strand-transfer inhibitor (INSTI), and to discuss its role in the treatment of HIV-1-infected patients.
  
  
  METHODS
  PubMed articles indexed through August 2013 were identified using the search terms S/GSK1349572, dolutegravir, and integrase inhibitor. Information was also identified from the package insert, cited publication references, professional meeting abstracts, and the ClinicalTrials.gov registry.
  
  
  METHODS
  English language articleswere selected for evaluation, with preference given to safety, efficacy, and pharmacokinetic studies conducted in HIV-1-infected patients.
  
  
  RESULTS
  Dolutegravir is a new INSTI approved for combination treatment in HIV-1-infected adults and adolescent children. Four phase 3 studies provide the basis for current labeling in antiretroviral-naïve and antiretroviral-experienced adults. Results from these studies demonstrate that dolutegravir is noninferior in efficacy to raltegravir in antiretroviral-naïve patients and superior in antiretroviral-experienced patients. Superiority to efavirenz and darunavir/ritonavir was also demonstrated in antiretroviral-naïve patients. Dolutegravir is well tolerated, exhibits low potential for drug-drug interactions, and has a long serum half-life, allowing it to be administered once-daily in patients without preexisting INSTI resistance. Twice-daily administration is recommended in patients with known or suspected resistance mutations to first-generation INSTIs. Mild elevations in serum creatinine occur following dolutegravir initiation from inhibition of renal organic cation transporter 2 but do not reflect changes in glomerular filtration.
  
  
  CONCLUSIONS
  Dolutegravir is the first second-generation INSTI and exhibits several advantages over current integrase inhibitors and other preferred antiretrovirals. Long-term efficacy and safety are needed to define dolutegravir's role in treatment.
authors.affiliation: University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: R Chris
authors.initials: RC
authors.lastname: Rathbun
authors.forename: Staci M
authors.initials: SM
authors.lastname: Lockhart
authors.forename: Misty M
authors.initials: MM
authors.lastname: Miller
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Liedtke
mesh_terms: D000480:Alkynes; D048588:Benzoxazines / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003521:Cyclopropanes; D004338:Drug Combinations; D004347:Drug Interactions; D015658:HIV Infections / Q000188:drug therapy*; D019428:HIV Integrase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D006207:Half-Life; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D011760:Pyrrolidinones / Q000627:therapeutic use; D000068898:Raltegravir Potassium; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D019438:Ritonavir / Q000627:therapeutic use; D000099226:Dolutegravir
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D004338:Drug Combinations; D019428:HIV Integrase Inhibitors; D017320:HIV Protease Inhibitors; D006575:Heterocyclic Compounds, 3-Ring; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium; D018894:Reverse Transcriptase Inhibitors; D019438:Ritonavir; D000099226:Dolutegravir; C098320:efavirenz
keywords: antiretroviral; dolutegravir; integrase inhibitor