Rare emergence of drug resistance in HIV-1 treatment-naïve patients after 48 weeks of treatment with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide.

HIV Clinical Trials
Nicolas A MargotChristian Callebaut

Abstract

Tenofovir alafenamide (TAF), a novel prodrug of the NtRTI tenofovir (TFV), delivers TFV-diphosphate (TFV-DP) to target cells more efficiently than the current prodrug, tenofovir disoproxil fumarate (TDF), with a 90% reduction in TFV plasma exposure. TAF, within the fixed dose combination of elvitegravir /cobicistat / emtricitabine (FTC)/TAF (E/C/F/TAF), has been evaluated in one Phase 2 and two Phase 3 randomized, double-blinded studies in HIV-infected treatment-naive patients, comparing E/C/F/TAF to E/C/F/TDF. In these studies, the TAF-containing group demonstrated non-inferior efficacy to the TDF-containing comparator group with 91.9% of E/C/F/TAF patients having <50 copies/mL of HIV-1 RNA at week 48. An integrated resistance analysis across these three studies was conducted, including HIV-1 genotypic analysis at screening, and genotypic/phenotypic analysis for patients with HIV-1 RNA>400 copies/mL at virologic failure. Pre-existing primary resistance-associated mutations (RAMs) were observed at screening among the 1903 randomized and treated patients: 7.5% had NRTI-RAMs, 18.2% had NNRTI-RAMs, and 3.4% had primary PI-RAMs. Pre-treatment RAMs did not influence treatment response at Week 48. In the E/C/F/TAF group, resistance d...Continue Reading

References

Mar 18, 2000·Antimicrobial Agents and Chemotherapy·C J PetropoulosJ M Whitcomb
Sep 21, 2001·Nucleosides, Nucleotides & Nucleic Acids·E J EisenbergW A Lee
Dec 4, 2009·Immunology Letters·Michael ReichTimo Burster
Apr 14, 2010·Expert Opinion on Drug Safety·Sonia Rodriguez-NóvoaVincent Soriano
Mar 16, 2011·Laboratory Investigation; a Journal of Technical Methods and Pathology·James J KohlerWilliam Lewis
Sep 1, 2011·AIDS Research and Human Retroviruses·Toshibumi TaniguchiEdgar Turner Overton
Sep 15, 2012·BMC Genomics·Xiao YangMatthew R Henn
Jun 29, 2013·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Peter J RuaneKitty Yale
Sep 18, 2013·Current Medical Research and Opinion·Isabel AldirMargarida Serrado
Dec 12, 2013·Journal of Acquired Immune Deficiency Syndromes : JAIDS·David B HannaRobert C Kaplan
May 30, 2014·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Paul E SaxScott McCallister
Apr 15, 2015·Antimicrobial Agents and Chemotherapy·Eisuke MurakamiAdrian S Ray
Jul 8, 2015·Antimicrobial Agents and Chemotherapy·Nicolas A MargotChristian Callebaut

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Citations

Nov 22, 2016·The Journal of Infectious Diseases·Huldrych F Günthard, Alexandra U Scherrer
Jan 25, 2017·Expert Review of Anti-infective Therapy·Arkaitz Imaz, Daniel Podzamczer
Jul 31, 2020·The Journal of Antimicrobial Chemotherapy·Jean L MbisaAnna Maria Geretti

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