title: Long-lasting persistence of integrase resistance mutations in HIV-2-infected patients after raltegravir withdrawal.
abstract: BACKGROUND
  Little is known in HIV-2 infection about the kinetics of disappearance of raltegravir (RAL)-resistant virus after RAL withdrawal.
  
  
  METHODS
  RAL was interrupted in four highly antiretroviral-experienced HIV-2-infected patients exhibiting a virological failure when receiving RAL. Integrase gene was sequenced from plasma samples collected at the time of RAL failure and at further time points following RAL withdrawal.
  
  
  RESULTS
  At the time of RAL withdrawal, virus exhibited different integrase resistance pathways: G140S/Q148R, E92Q/N155H, T97A/N155H and T97A/Y143C. In patient 1, the G140S/Q148R double-mutant was still detected at month (M)7 and at M11 after stopping RAL, but was no longer detected at M15. Regarding patient 2, the double-mutant E92Q/N155H was still present at M2 and M8 after stopping RAL, and was no longer detected at M12. In patient 3, RAL-resistant virus with T97A/N155H mutations were still present 1 month after stopping RAL, and were no longer detected at M14. Regarding patient 4, the mutant T97A/Y143C was still detected at M1 and M3 following RAL withdrawal. At M18 after RAL stop, integrase genotypic pattern evolved to T97A/Y143G.
  
  
  CONCLUSIONS
  Persistence of HIV-2 RAL-resistant mutants was observed in all the key genetic RAL resistance pathways. These findings have clinical implications especially in HIV-2-infected patients for whom therapeutic arsenal is limited compared to HIV-1, since the persistence of resistant mutants might compromise the possible efficacy of upcoming second-generation integrase inhibitors.
authors: Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Bichat-Claude Bernard, Laboratoire de Virologie, Paris, France. charlotte.charpentier@bch.aphp.fr
authors: Charlotte
authors: C
authors: Charpentier
authors: Lucile
authors: L
authors: Larrouy
authors: Sophie
authors: S
authors: Matheron
authors: Florence
authors: F
authors: Damond
authors: Olivier
authors: O
authors: Delelis
authors: Jean-François
authors: JF
authors: Mouscadet
authors: Pauline
authors: P
authors: Campa
authors: Geneviève
authors: G
authors: Chêne
authors: Françoise
authors: F
authors: Brun-Vézinet
authors: Diane
authors: D
authors: Descamps
mesh_terms: D024882:Drug Resistance, Viral / Q000235:genetics; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy*; D019427:HIV Integrase / Q000235:genetics*; D019428:HIV Integrase Inhibitors / Q000627:therapeutic use*; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015498:HIV-2 / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics*; D011760:Pyrrolidinones / Q000627:therapeutic use*; D000068898:Raltegravir Potassium; D016879:Salvage Therapy; D019562:Viral Load; D028761:Withholding Treatment
chemical_list: D019428:HIV Integrase Inhibitors; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium; D019427:HIV Integrase; C514802:p31 integrase protein, Human immunodeficiency virus 2; C072416:reverse transcriptase, Human immunodeficiency virus 2; D054303:HIV Reverse Transcriptase