Unknown

Dataset Information

0

In vivo emergence of vicriviroc resistance in a human immunodeficiency virus type 1 subtype C-infected subject.


ABSTRACT: Little is known about the in vivo development of resistance to human immunodeficiency virus type 1 (HIV-1) CCR5 antagonists. We studied 29 subjects with virologic failure from a phase IIb study of the CCR5 antagonist vicriviroc (VCV) and identified one individual with HIV-1 subtype C who developed VCV resistance. Studies with chimeric envelopes demonstrated that changes within the V3 loop were sufficient to confer VCV resistance. Resistant virus showed VCV-enhanced replication, cross-resistance to another CCR5 antagonist, TAK779, and increased sensitivity to aminooxypentane-RANTES and the CCR5 monoclonal antibody HGS004. Pretreatment V3 loop sequences reemerged following VCV discontinuation, implying that VCV resistance has associated fitness costs.

SUBMITTER: Tsibris AM 

PROVIDER: S-EPMC2519584 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature

altmetric image

Publications

In vivo emergence of vicriviroc resistance in a human immunodeficiency virus type 1 subtype C-infected subject.

Tsibris Athe M N AM   Sagar Manish M   Gulick Roy M RM   Su Zhaohui Z   Hughes Michael M   Greaves Wayne W   Subramanian Mani M   Flexner Charles C   Giguel Françoise F   Leopold Kay E KE   Coakley Eoin E   Kuritzkes Daniel R DR  

Journal of virology 20080521 16


Little is known about the in vivo development of resistance to human immunodeficiency virus type 1 (HIV-1) CCR5 antagonists. We studied 29 subjects with virologic failure from a phase IIb study of the CCR5 antagonist vicriviroc (VCV) and identified one individual with HIV-1 subtype C who developed VCV resistance. Studies with chimeric envelopes demonstrated that changes within the V3 loop were sufficient to confer VCV resistance. Resistant virus showed VCV-enhanced replication, cross-resistance  ...[more]

Similar Datasets

| S-EPMC86447 | biostudies-literature
| S-EPMC2812128 | biostudies-literature
| S-EPMC5821307 | biostudies-literature
| S-EPMC525043 | biostudies-literature
| S-EPMC3719840 | biostudies-other
| S-EPMC2738176 | biostudies-literature
| S-EPMC525063 | biostudies-literature
| S-EPMC7035011 | biostudies-literature
| S-EPMC103818 | biostudies-literature
| S-EPMC2708608 | biostudies-literature