부산대학교 도서관

Objectives The mechanism of raltegravir ( RAL)-resistant evolutions has not already been elucidated. Because the emergence of RAL resistance is usually initiated by the N155 H mutant, we assessed the role of minor N155 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 N155 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 N155 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 N155 H was detected at different levels in three patients displaying the N155 H pathway and gradually declined when the double mutant Q148 H+ G140 S was selected in one patient. In two patients with the Q148 H resistance pathway, no N155 H variant was identified by AS-PCR in either viral RNA or DNA. Conclusions The N155 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 N155 H is very infrequent and, if selected during RAL failure, the N155 H mutant disappears quickly after RAL withdrawal. [ABSTRACT FROM AUTHOR]