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

• Verfasst von: Fun, Axel [VerfasserIn]
• Verfasst von: Buchholz, Bernd [VerfasserIn]
• Titel: Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance
• Verf.angabe: 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
• E-Jahr: 2018
• Jahr: 05 January 2018
• Umfang: 13 S.
• Fussnoten: Gesehen am 03.09.2019
• Titel Quelle: Enthalten in: Retrovirology
• Ort Quelle: London : BioMed Central, 2004
• Jahr Quelle: 2018
• Band/Heft Quelle: 15(2018) Artikel-Nummer 1, 13 Seiten
• ISSN Quelle: 1742-4690
• DOI: doi:10.1186/s12977-017-0384-z
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1675779570

Abstract

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.