Show simple item record

dc.contributor.authorSiedner, Mark J.
dc.contributor.authorMoorhouse, Michelle A.
dc.contributor.authorSimmons, Bryony
dc.contributor.authorde Oliveira, Tulio
dc.contributor.authorLessells, Richard
dc.contributor.authorGiandhari, Jennifer
dc.contributor.authorKemp, Stephen A.
dc.contributor.authorChimukangara, Benjamin
dc.contributor.authorAkpomiemie, Godspower
dc.contributor.authorSerenata, Celicia M.
dc.contributor.authorVenter, Willem D. F.
dc.contributor.authorHill, Andrew
dc.contributor.authorGupta, Ravindra K.
dc.date.accessioned2020-12-02T16:12:07Z
dc.date.available2020-12-02T16:12:07Z
dc.date.issued2020-12-01
dc.date.submitted2020-07-19
dc.identifier.others41467-020-19801-x
dc.identifier.other19801
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/313911
dc.description.abstractAbstract: Little is known about the impact of pretreatment drug resistance (PDR) on the efficacy of second generation integrase inhibitors. We sequenced pretreatment plasma specimens from the ADVANCE trial (NCT03122262). Our primary outcome was 96-week virologic success, defined as a sustained viral load <1000 copies/mL from 12 weeks onwards, <200 copies/mL from 24 weeks onwards, and <50 copies/mL after 48 weeks. Here we report how this outcome was impacted by PDR, defined by the World Health Organization (WHO) mutation list. Of 1053 trial participants, 874 (83%) have successful sequencing, including 289 (33%) randomized to EFV-based therapy and 585 (67%) randomized to DTG-based therapy. Fourteen percent (122/874) have ≥1 WHO-defined mutation, of which 98% (120/122) are NNRTI mutations. Rates of virologic suppression are lower in the total cohort among those with PDR 65% (73/112) compared to those without PDR (85% [605/713], P < 0.001), and for those on EFV-based treatment (60% [12/20] vs 86% [214/248], P = 0.002) and for those on DTG-based treatment (61/92 [66%] vs 84% [391/465] P < 0.001, P for interaction by regimen 0.49). Results are similar in multivariable models adjusted for clinical characteristics and adherence. NNRTI resistance prior to treatment is associated with long-term failure of integrase inhibitor-containing first-line regimens, and portends high rates of first-line failure in sub Saharan Africa.
dc.languageen
dc.publisherNature Publishing Group UK
dc.rightsAttribution 4.0 International (CC BY 4.0)en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectArticle
dc.subject/631/326/596/1787
dc.subject/692/4017
dc.subject/45
dc.subject/45/88
dc.subjectarticle
dc.titleReduced efficacy of HIV-1 integrase inhibitors in patients with drug resistance mutations in reverse transcriptase
dc.typeArticle
dc.date.updated2020-12-02T16:12:07Z
prism.issueIdentifier1
prism.publicationNameNature Communications
prism.volume11
dc.identifier.doi10.17863/CAM.61014
dcterms.dateAccepted2020-10-28
rioxxterms.versionofrecord10.1038/s41467-020-19801-x
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidSiedner, Mark J. [0000-0003-3506-842X]
dc.contributor.orcidMoorhouse, Michelle A. [0000-0002-8410-3247]
dc.contributor.orcidSimmons, Bryony [0000-0002-3207-9935]
dc.contributor.orcidLessells, Richard [0000-0003-0926-710X]
dc.contributor.orcidSerenata, Celicia M. [0000-0001-7921-0948]
dc.contributor.orcidGupta, Ravindra K. [0000-0001-9751-1808]
dc.identifier.eissn2041-1723


Files in this item

Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record

Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's licence is described as Attribution 4.0 International (CC BY 4.0)