title: Virological evidence supporting the use of raltegravir in HIV post-exposure prophylaxis regimens.
abstract: BACKGROUND
  The goal of post-exposure prophylaxis (PEP) for HIV is to prevent the establishment of a persistent infection following exposure to the virus. Integrase inhibitors have several potential advantages in PEP regimens, including the capacity to inhibit integration of HIV genomes that have already proceeded through reverse transcription, thereby becoming refractory to reverse transcriptase inhibitors. We sought to determine if integrase inhibitors extend the window of time during which PEP intervention might be successful.
  
  
  METHODS
  Primary costimulated CD4(+) T-cells or macrophages were infected with a luciferase-bearing HIV reporter virus, permitting sensitive detection of viral gene expression under different drug treatment conditions. Relevant antiretroviral agents were added at various pre- or post-infection time points.
  
  
  RESULTS
  We showed that raltegravir effectively blocks HIV infection, even when cells are challenged with a large amount of virus. We also demonstrated that during infection of both primary costimulated CD4(+) T-cells and primary macrophages, raltegravir can inhibit infection when added at later post-infection time points than the reverse transcriptase inhibitor efavirenz.
  
  
  CONCLUSIONS
  This longer post-infection efficacy window, coupled with favourable pharmacokinetic properties and low toxicity, suggest that raltegravir may prove useful in HIV PEP.
authors: Department of Medicine, Division of Hematology and Oncology, UCLA, Los Angeles, CA, USA.
authors: Matthew D
authors: MD
authors: Marsden
authors: Paul A
authors: PA
authors: Krogstad
authors: Jerome A
authors: JA
authors: Zack
mesh_terms: D000480:Alkynes; D048588:Benzoxazines / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000821:virology; D003521:Cyclopropanes; D015967:Gene Expression Regulation, Viral; D017930:Genes, Reporter; D005814:Genes, Viral; D006678:HIV / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D019428:HIV Integrase Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D008156:Luciferases / Q000235:genetics; D008264:Macrophages / Q000187:drug effects / Q000821:virology; D008826:Microbial Sensitivity Tests / Q000379:methods; D056990:Post-Exposure Prophylaxis / Q000379:methods*; D011760:Pyrrolidinones / Q000493:pharmacokinetics / Q000494:pharmacology*; D000068898:Raltegravir Potassium; D013997:Time Factors
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D019428:HIV Integrase Inhibitors; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium; D008156:Luciferases; C098320:efavirenz