Document Detail


Longitudinal analysis of integrase N155H variants in heavily treated patients failing raltegravir-based regimens.
MedLine Citation:
PMID:  22994529     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
OBJECTIVES: 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:
Hl Nguyen; C Charpentier; N Nguyen; P de Truchis; J-M Molina; K Ruxrungtham; C Delaugerre
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-9-20
Journal Detail:
Title:  HIV medicine     Volume:  -     ISSN:  1468-1293     ISO Abbreviation:  HIV Med.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-9-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100897392     Medline TA:  HIV Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 British HIV Association.
Affiliation:
Virology Department, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), INSERM U941, Paris Diderot University, Sorbonne Paris Cité, Paris, France; Vaccine and Cellular Immunology Laboratory, Chula Vaccine Research Center, Bangkok, Thailand; Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Department of HIV/AIDS, National Institute of Hygiene and Epidemiology, Hanoi, Vietnam.
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