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Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance

Emergence of resistance against integrase inhibitor raltegravir in human immunodeficiency virus type 1 (HIV-1) patients is generally associated with selection of one of three signature mutations: Y143C/R, Q148K/H/R or N155H, representing three distinct resistance pathways. The mechanisms that drive...

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Bibliographic Details
Main Authors: Fun, Axel (Author) , Buchholz, Bernd (Author)
Format: Article (Journal)
Language:English
Published: 05 January 2018
In: Retrovirology
Year: 2018, Volume: 15
ISSN:1742-4690
DOI:10.1186/s12977-017-0384-z
Online Access:Verlag, Volltext: https://doi.org/10.1186/s12977-017-0384-z
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Author Notes:Axel Fun, Thomas Leitner, Linos Vandekerckhove, Martin Däumer, Alexander Thielen, Bernd Buchholz, Andy I.M. Hoepelman, Elizabeth H. Gisolf, Pauline J. Schipper, Annemarie M.J. Wensing and Monique Nijhuis
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Summary:Emergence of resistance against integrase inhibitor raltegravir in human immunodeficiency virus type 1 (HIV-1) patients is generally associated with selection of one of three signature mutations: Y143C/R, Q148K/H/R or N155H, representing three distinct resistance pathways. The mechanisms that drive selection of a specific pathway are still poorly understood. We investigated the impact of the HIV-1 genetic background and population dynamics on the emergence of raltegravir resistance. Using deep sequencing we analyzed the integrase coding sequence (CDS) in longitudinal samples from five patients who initiated raltegravir plus optimized background therapy at viral loads > 5000 copies/ml. To investigate the role of the HIV-1 genetic background we created recombinant viruses containing the viral integrase coding region from pre-raltegravir samples from two patients in whom raltegravir resistance developed through different pathways. The in vitro selections performed with these recombinant viruses were designed to mimic natural population bottlenecks.
Item Description:Gesehen am 03.09.2019
Physical Description:Online Resource
ISSN:1742-4690
DOI:10.1186/s12977-017-0384-z

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