Minority and majority pretreatment HIV-1 drug resistance associated with failure of first-line nonnucleoside reverse-transcriptase inhibitor antiretroviral therapy in Kenyan women

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dc.contributor.authorMilne, Ross S.en
dc.contributor.authorSilverman, Rachel A.en
dc.contributor.authorBeck, Ingrid A.en
dc.contributor.authorMcKernan-Mullin, Jenniferen
dc.contributor.authorDeng, Wenjieen
dc.contributor.authorSibley, Thomas R.en
dc.contributor.authorDross, Sandraen
dc.contributor.authorKiarie, James N.en
dc.contributor.authorSakr, Samah R.en
dc.contributor.authorCoombs, Robert W.en
dc.contributor.authorChung, Michael H.en
dc.contributor.authorFrenkel, Lisa M.en
dc.coverage.countryKenyaen
dc.date.accessioned2022-01-13T16:26:27Zen
dc.date.available2022-01-13T16:26:27Zen
dc.date.issued2019-05-01en
dc.date.updated2022-01-13T16:26:25Zen
dc.description.abstractObjectives: Among women initiating first-line nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based-ART with and without a history of single-dose nevirapine (sdNVP) with or without zidovudine with or without lamivudine (ZDV with and without 3TC) for prevention of mother-to-child HIV transmission (PMTCT), we hypothesized that pre-ART HIV-drug resistance would be associated with virologic failure. Design/Methods: In a prospectively enrolled study, three genotypic drug-resistance assays [oligonucleotide-ligation-assay (OLA), consensus sequencing, and next-generation sequencing by Illumina] were retrospectively performed to detect pre-ART drug resistance. Minority or majority drug-resistant variants identified in pre-ART RNA and/or DNA, a history of antiretrovirals for PMTCT, and other risk factors were assessed for association with virologic failure. Results: Failure occurred in 38/169 (22.5%) women, and was associated with pre-ART drug resistance detected by any assay (OLA of plasma or PBMC, consensus sequencing of PBMC and/or plasma, and next-generation sequencing of PBMC at frequencies of at least 10% and as minority variants; all Pā€Š<ā€Š0.0001). Failure was also associated with PMTCT using sdNVP and ZDV with or without 3TC, but not sdNVP only; however, the longer time-interval between PMTCT and ART initiation observed for sdNVP-only women showed no interaction with failure. Viral loads and OLA of PBMC in longitudinal specimens demonstrated rapid failure and emergence of drug resistance, particularly among sdNVP and ZDV with or without 3TC-experienced women with pre-ART drug-resistant minority variants by next-generation sequencing but without drug resistance by OLA or consensus sequencing. Conclusion: Pre-ART drug resistance was detected similarly by OLA of PBMC or plasma and by consensus sequencing, and was associated with virologic failure soon after initiation of first-line NVP-based ART. A history of sdNVP and ZDV with or without 3TC for PMTCT or minority variants detected by next-generation sequencing identified additional women with failure. These findings emphasize the value of assessing individual antiretroviral history, particularly nonsuppressive antiretrovirals with at least two drug classes, and testing for pre-ART drug resistance, including minority variants.en
dc.description.versionAccepted versionen
dc.format.extentPages 941-951en
dc.format.extent11 page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1097/QAD.0000000000002134en
dc.identifier.eissn1473-5571en
dc.identifier.issn0269-9370en
dc.identifier.issue6en
dc.identifier.orcidSilverman, Rachel [0000-0003-3082-9664]en
dc.identifier.other00002030-201905010-00002 (PII)en
dc.identifier.pmid30946148en
dc.identifier.urihttp://hdl.handle.net/10919/107609en
dc.identifier.volume33en
dc.language.isoenen
dc.publisherLippincott Williams & Wilkinsen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000480695100002&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectImmunologyen
dc.subjectInfectious Diseasesen
dc.subjectVirologyen
dc.subjectantiretroviral therapyen
dc.subjectHIV drug resistanceen
dc.subjectnevirapineen
dc.subjectprevention of mother-to-child transmissionen
dc.subjectquasispeciesen
dc.subjectWomenen
dc.subjectOligonucleotide Ligation Assayen
dc.subjectSingle-Dose Nevirapineen
dc.subjectTo-Child Transmissionen
dc.subjectDolutegravir Monotherapyen
dc.subjectPreexposure Prophylaxisen
dc.subjectVirological Failureen
dc.subjectCross-Resistanceen
dc.subjectNaive Adultsen
dc.subjectMutationsen
dc.subjectVariantsen
dc.subject06 Biological Sciencesen
dc.subject11 Medical and Health Sciencesen
dc.subject17 Psychology and Cognitive Sciencesen
dc.subjectVirologyen
dc.subject.meshHumansen
dc.subject.meshHIV-1en
dc.subject.meshHIV Infectionsen
dc.subject.meshAnti-Retroviral Agentsen
dc.subject.meshRetrospective Studiesen
dc.subject.meshDrug Resistance, Viralen
dc.subject.meshGenotypeen
dc.subject.meshMutationen
dc.subject.meshAdolescenten
dc.subject.meshAdulten
dc.subject.meshKenyaen
dc.subject.meshFemaleen
dc.subject.meshYoung Adulten
dc.subject.meshGenotyping Techniquesen
dc.titleMinority and majority pretreatment HIV-1 drug resistance associated with failure of first-line nonnucleoside reverse-transcriptase inhibitor antiretroviral therapy in Kenyan womenen
dc.title.serialAIDSen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Veterinary Medicineen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/Population Health Sciencesen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen

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