OBJECTIVES: @entity645 resistance to the integrase inhibitor @entity5197 in treated @entity1 is characterized by distinct resistance pathways. We hypothesize that differences in the in vivo dynamics of @entity645 resistance to @entity5197 are due to the genetic context of the integrase present at baseline. @entity1 AND METHODS: We studied four @entity1 whose viruses evolved towards different resistance pathways. The integrase baseline sequences were inserted into a reference clone. Primary resistance mutations were then introduced and their impact on viral @entity124 ( @entity124 ) and resistance was measured. RESULTS: @entity1 A and B experienced emergence and persistence of mutation @entity23511 under @entity5197 therapy. In the integrase sequence from @entity1 A, @entity23511 conferred potent resistance coupled with a lower impact on @entity124 than @entity25425 . In @entity1 B, instead, selection of @entity23511 could be explained by the dramatic loss of @entity124 induced by the alternative @entity25425 mutation. In @entity1 C, @entity23511 initially emerged and was later replaced by @entity25425 . In this integrase context, @entity23511 resulted in higher @entity124 but lower resistance than @entity25425 . In @entity1 D, @entity25425 rapidly emerged without appearance of @entity23511 . This was the only @entity1 for whom @entity25425 conferred higher @entity124 and resistance than @entity23511 . CONCLUSIONS: The emergence of different resistance mutations in @entity1 was in full agreement with the impact of mutations in different baseline integrase contexts. Evolution towards different resistance genotypes is thus largely determined by the capacity of different integrase sequences present at baseline to minimize the effect of mutations on virus @entity124 while allowing expression of resistance.

Impact of the @entity645 integrase genetic context on the phenotypic expression and in vivo emergence of XXXX resistance mutations.

@entity1 :: ('9606', 'Species') :: ['Patients', 'patients', 'patient', 'PATIENTS', 'Patient'] @entity124 :: ('MESH:D053842', 'Disease') :: ['RC', 'replication capacity'] @entity645 :: ('57667', 'Species') :: ['HIV'] @entity25425 :: ('p|SUB|Q|148|H', 'ProteinMutation') :: ['Q148H'] @entity23511 :: ('p|SUB|N|155|H', 'ProteinMutation') :: ['N155H'] @entity5197 :: ('MESH:C507898', 'Chemical') :: ['raltegravir']
@entity5197 :: (MESH:C507898,Chemical) :: ['raltegravir']
