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J Antimicrob Chemother. 2012 Jun;67(6):1459-61. doi: 10.1093/jac/dks067. Epub 2012 Mar 1.

Prevalence of subtype-related polymorphisms associated with in vitro resistance to attachment inhibitor BMS-626529 in HIV-1 'non-B'-infected patients.

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  • 1Assistance Publique-Hôpitaux de Paris, Hôpital Bichat-Claude Bernard, Laboratoire de Virologie, and EA 4409 Paris-Diderot University, Paris 7, Paris, France. charlotte.charpentier@bch.aphp.fr

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 AND METHODS:

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.

PMID:
22382470
[PubMed - indexed for MEDLINE]
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