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 DF
dc.contributor.authorHill, Andrew
dc.contributor.authorGupta, Ravindra K
dc.date.accessioned2020-12-08T00:31:19Z
dc.date.available2020-12-08T00:31:19Z
dc.date.issued2020-12-01
dc.identifier.issn2041-1723
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/314852
dc.description.abstractLittle 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.format.mediumElectronic
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectHumans
dc.subjectHIV-1
dc.subjectHIV Infections
dc.subjectHIV Integrase
dc.subjectHIV Integrase Inhibitors
dc.subjectAnti-HIV Agents
dc.subjectViral Load
dc.subjectCohort Studies
dc.subjectDrug Resistance, Viral
dc.subjectMutation
dc.subjectAdult
dc.subjectAfrica South of the Sahara
dc.subjectFemale
dc.subjectMale
dc.subjectHIV Reverse Transcriptase
dc.titleReduced efficacy of HIV-1 integrase inhibitors in patients with drug resistance mutations in reverse transcriptase.
dc.typeArticle
prism.issueIdentifier1
prism.publicationDate2020
prism.publicationNameNat Commun
prism.startingPage5922
prism.volume11
dc.identifier.doi10.17863/CAM.61958
dcterms.dateAccepted2020-10-28
rioxxterms.versionofrecord10.1038/s41467-020-19801-x
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2020-12
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
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (108082/A/15/Z)
cam.issuedOnline2020-12


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

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