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Longitudinal analysis of integrase N 155 H variants in heavily treated patients failing raltegravir‐based regimens
Author(s) -
Nguyen HL,
Charpentier C,
Nguyen N,
Truchis P,
Molina JM,
Ruxrungtham K,
Delaugerre C
Publication year - 2013
Publication title -
hiv medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 79
eISSN - 1468-1293
pISSN - 1464-2662
DOI - 10.1111/j.1468-1293.2012.01039.x
Subject(s) - raltegravir , integrase , mutant , medicine , genotyping , mutation , integrase inhibitor , allele , polymerase chain reaction , microbiology and biotechnology , viral load , virology , genotype , biology , genetics , human immunodeficiency virus (hiv) , gene , antiretroviral therapy
Objectives The mechanism of raltegravir ( RAL )‐resistant evolutions has not already been elucidated. Because the emergence of RAL resistance is usually initiated by the N 155 H mutant, we assessed the role of minor N 155 H ‐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 N 155 H 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 N 155 H ‐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 N 155 H was detected at different levels in three patients displaying the N 155 H pathway and gradually declined when the double mutant Q 148 H + G 140 S was selected in one patient. In two patients with the Q 148 H resistance pathway, no N 155 H variant was identified by AS‐PCR in either viral RNA or DNA . Conclusions The N 155 H 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 N 155 H is very infrequent and, if selected during RAL failure, the N 155 H mutant disappears quickly after RAL withdrawal.