title: Longitudinal analysis of integrase N155H variants in heavily treated patients failing raltegravir-based regimens.
abstract: OBJECTIVE
  The mechanism of raltegravir (RAL)-resistant evolutions has not already been elucidated. Because the emergence of RAL resistance is usually initiated by the N155H mutant, we assessed the role of minor N155H-mutated variants in circulating RNA and archived DNA in five heavily treated patients experiencing long-term RAL therapy failure and harbouring three different resistance profiles determined by standard genotyping.
  
  
  METHODS
  Allele-specific polymerase chain reaction (AS-PCR) was used to detect N155H mutants in longitudinal stored plasma and whole-blood samples before, during and after RAL-based regimens in five patients infected with the HIV-1 B subtype.
  
  
  RESULTS
  No minor N155H-mutated variant was found by AS-PCR in either plasma or whole-blood samples collected at baseline and after RAL withdrawal in any of the five patients. During RAL failure, the mutation N155H was detected at different levels in three patients displaying the N155H pathway and gradually declined when the double mutant Q148H+G140S was selected in one patient. In two patients with the Q148H resistance pathway, no N155H variant was identified by AS-PCR in either viral RNA or DNA.
  
  
  CONCLUSIONS
  The N155H mutation present at various levels from minority to majority showed no relationship with the three RAL-associated resistance profiles, suggesting that this mutant may not play a role in determining different resistance profiles. Moreover, pre-existing N155H is very infrequent and, if selected during RAL failure, the N155H mutant disappears quickly after RAL withdrawal.
authors.affiliation: Virology Department, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris, INSERM U941, Paris Diderot University, Sorbonne Paris Cité, Paris, France.
authors.forename: H L
authors.initials: HL
authors.lastname: Nguyen
authors.forename: C
authors.initials: C
authors.lastname: Charpentier
authors.forename: N
authors.initials: N
authors.lastname: Nguyen
authors.forename: P
authors.initials: P
authors.lastname: de Truchis
authors.forename: J-M
authors.initials: JM
authors.lastname: Molina
authors.forename: K
authors.initials: K
authors.lastname: Ruxrungtham
authors.forename: C
authors.initials: C
authors.lastname: Delaugerre
mesh_terms: D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral / Q000187:drug effects* / Q000235:genetics; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D019427:HIV Integrase / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D019428:HIV Integrase Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D011760:Pyrrolidinones / Q000494:pharmacology*; D012367:RNA, Viral; D000068898:Raltegravir Potassium; D012189:Retrospective Studies; D016879:Salvage Therapy; D017423:Sequence Analysis, RNA; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D019428:HIV Integrase Inhibitors; D011760:Pyrrolidinones; D012367:RNA, Viral; D000068898:Raltegravir Potassium; D019427:HIV Integrase