title: Efficacy of raltegravir switching strategies in HIV-infected patients with suppressed viraemia according to the genotypic sensitivity score.
abstract: OBJECTIVE
  The lack of antiretroviral (ARV) backbone activity associated with raltegravir has been proposed as the main explanation for virological relapse observed in patients with undetectable viraemia who are switched from a ritonavir-boosted protease inhibitor (PI) to raltegravir. However ARV activity remains difficult to assess in this context. The aim of our study was to precisely assess the ARV backbone activity in patients with undetectable viraemia who underwent raltegravir switching strategies and to evaluate the efficacy of such switching strategies based on the genotypic sensitivity score (GSS).
  
  
  METHODS
  Patients with a plasma human immunodeficiency virus type 1 (HIV-1) RNA level of <50 copies/mL on a stable two ARV-class regimen were enrolled if they switched one of their ARV drugs to raltegravir 400 mg twice daily. The GSS was calculated using a genotyping test performed on the HIV-1 RNA of the last plasma measurement with a HIV-1 RNA level of >50 copies/mL before the switch and on the results of all previous genotyping tests. The primary endpoint was the proportion of patients with a plasma HIV-1 RNA level of <50 copies/mL at week 24.
  
  
  RESULTS
  Fifty-six patients were enrolled in this study. The proportion of patients with a plasma HIV-1 RNA level of <50 copies/mL at week 24 was 92.9 % (range 83.0-97.2 %) in the intent-to-treat analysis and 98.1 % (90.0-99.7 %) in per-protocol analysis. When the backbone was fully active, the proportion was 100.0 % (86.7-100.0 %) at week 24 and week 48 in the per-protocol analysis. We observed a decrease in plasma total cholesterol and triglycerides of -12.7 % (p = 0.005) and -26.5 % (p = 0.001), respectively.
  
  
  CONCLUSIONS
  Raltegravir switching strategies are effective when the associated backbone is fully active according to the GSS. In the context of undetectable viraemia, where ARV activity remains difficult to assess, the determination of the GSS requires the entire ARV history of the patient and all previous HIV-RNA genotyping test results.
authors.affiliation: Service des Maladies Infectieuses et Tropicales, Groupe Hospitalier Pitié-Salpêtrière, 47/83 Boulevard de l'Hôpital, 75651, Paris Cedex 13, France, fabienne.caby@psl.aphp.fr.
authors.forename: F
authors.initials: F
authors.lastname: Caby
authors.forename: L
authors.initials: L
authors.lastname: Schneider
authors.forename: C
authors.initials: C
authors.lastname: Blanc
authors.forename: C
authors.initials: C
authors.lastname: Soulié
authors.forename: M
authors.initials: M
authors.lastname: Tindel
authors.forename: G
authors.initials: G
authors.lastname: Peytavin
authors.forename: R
authors.initials: R
authors.lastname: Agher
authors.forename: M A
authors.initials: MA
authors.lastname: Valantin
authors.forename: R
authors.initials: R
authors.lastname: Tubiana
authors.forename: M
authors.initials: M
authors.lastname: Wirden
authors.forename: V
authors.initials: V
authors.lastname: Calvez
authors.forename: A G
authors.initials: AG
authors.lastname: Marcelin
authors.forename: C
authors.initials: C
authors.lastname: Katlama
mesh_terms: D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active; D024882:Drug Resistance, Viral; D005260:Female; D005602:France; D005838:Genotype; D006678:HIV / Q000187:drug effects*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D019428:HIV Integrase Inhibitors / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011760:Pyrrolidinones / Q000494:pharmacology*; D000068898:Raltegravir Potassium; D019438:Ritonavir / Q000494:pharmacology*; D014766:Viremia / Q000188:drug therapy* / Q000821:virology
chemical_list: D019428:HIV Integrase Inhibitors; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium; D019438:Ritonavir