Prevalence of subtype-related polymorphisms associated with in vitro resistance to attachment inhibitor BMS-626529 in HIV-1 'non-B'-infected patients.
J Antimicrob Chemother
; 67(6): 1459-61, 2012 Jun.
Article
en En
| MEDLINE
| ID: mdl-22382470
ABSTRACT
OBJECTIVES:
BMS-626529 is a member of the new drug class of HIV-1 attachment inhibitors currently in development. Mutations selected during in vitro experiments with BMS-626529 are located in the gp120 region L116P, A204D, M426L, M434I-V506M and M475I. A differential antiviral activity of BMS-626529 was observed depending of the viral subtype. The aim of our study was to assess the prevalence of subtype-related polymorphisms previously described as being associated with in vitro resistance to BMS-626529 in patients infected with different HIV-1 'non-B' subtypes. PATIENTS ANDMETHODS:
The prevalence of substitutions in gp120 was assessed in 85 HIV-infected patients (not previously treated with attachment inhibitors and infected with HIV-1 'non-B' subtypes) by performing direct sequencing of the gp120 region.RESULTS:
The most prevalent HIV-1 subtype was CRF02_AG (n = 46, 54%). The M426L substitution was found in virus from 10 patients (11.8%), mainly in subtypes D and CRF02_AG. The M434I substitution was found in virus from 11 patients (12.9%), mainly in subtypes CRF02_AG and CRF06_cpx. None of the CRF02_AG viruses harboured both M426L and M434I substitutions.CONCLUSIONS:
In our series, the M426L substitution in the gp120 region was detected in 46% and 7% of subtype D and CRF02_AG samples, respectively, and might affect the activity of BMS-626529 against these specific subtypes. Further studies are needed to better describe associations between HIV-1 'non-B'-subtype-related polymorphism profiles and the level of phenotypic resistance to attachment inhibitor BMS-626529.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Polimorfismo Genético
/
Proteína gp120 de Envoltorio del VIH
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VIH-1
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Fármacos Anti-VIH
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Inhibidores de Fusión de VIH
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Farmacorresistencia Viral
Tipo de estudio:
Prevalence_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
J Antimicrob Chemother
Año:
2012
Tipo del documento:
Article
País de afiliación:
Francia
Pais de publicación:
ENGLAND
/
ESCOCIA
/
GB
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GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
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SCOTLAND
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UK
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UNITED KINGDOM