HIV-1 Group O Integrase Displays Lower Enzymatic Efficiency and Higher Susceptibility to Raltegravir than HIV-1 Group M Subtype B Integrase

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HIV-1 group O integrase displays lower susceptibility to raltegravir and has a different mutational pathway for resistance than HIV-1 group M

INTRODUCTION HIV-1 group O (HIV-O) is a rare HIV-1 variant characterized by a high number of polymorphisms, especially in the integrase gene, e.g. positions L74I, S153A, G163Q and T206S. As HIV-O integrase enzymes have not previously been studied, our aim was to assess the impact of HIV-O integrase polymorphisms on susceptibility to integrase inhibitors and emergence of resistance associated mu...

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The HIV-1 integrase G118R mutation confers raltegravir resistance to the CRF02_AG HIV-1 subtype.

BACKGROUND Most of the previous studies that explored the molecular basis of raltegravir resistance were conducted studying the HIV-1 B subtype. It has been shown that the CRF02_AG subtype in relation to its natural integrase (IN) sequence could develop different genetic pathways associated with raltegravir resistance. The aim of this study was to explore resistance pathways preferably used by ...

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Genotypic/phenotypic patterns of HIV-1 integrase resistance to raltegravir.

OBJECTIVES To understand the dynamic viral evolution observed during failure on raltegravir-containing regimens, we studied the genotypic and phenotypic patterns of resistance to raltegravir and the residual replication capacity (rRC) of HIV-1 variants selected in vivo. METHODS Clonal genotypic analyses were performed on sequential HIV-1 integrase sequences amplified from 11 failing patients ...

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Raltegravir: the first HIV type 1 integrase inhibitor.

Raltegravir is the first approved human immunodeficiency virus type 1 (HIV-1) integrase inhibitor; it targets the strand transfer step of HIV-1 integration. Clinical trials have demonstrated that raltegravir-containing regimens have potent antiretroviral activity and are well tolerated in HIV-1-infected individuals. In antiretroviral treatment-experienced persons with drug-resistant HIV infecti...

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Raltegravir: first in class HIV integrase inhibitor

On October 16, 2007, the US Food and Drug Administration (FDA) approved raltegravir for treatment of human immunodeficiency virus (HIV)-1 infection in combination with other antiretroviral agents in treatment-experienced adult patients who have evidence of viral replication and HIV-1 strains resistant to multiple antiretroviral agents. Raltegravir is first in a novel class of antiretroviral dru...

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ژورنال

عنوان ژورنال: Antimicrobial Agents and Chemotherapy

سال: 2014

ISSN: 0066-4804,1098-6596

DOI: 10.1128/aac.03819-14