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Assessing transmissibility of HIV-1 drug resistance mutations from treated and from drug-naive individuals

2015-09-24Journal article Restricted access
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dc.contributor.authorWinand, Raf
dc.contributor.authorTheys, Kristof
dc.contributor.authorEusébio, Mónica
dc.contributor.authorAerts, Jan
dc.contributor.authorCamacho, Ricardo J.
dc.contributor.authorGomes, Perpétua
dc.contributor.authorSuchard, Marc A.
dc.contributor.authorVandamme, Anne-Mieke
dc.contributor.authorAbecasis, Ana B.
dc.contributor.authoron behalf of the Portuguese HIV-1 Resistance Study Group
dc.date.accessioned2017-05-26T12:00:13Z
dc.date.available2017-05-26T12:00:13Z
dc.date.issued2015-09-24
dc.description.abstractOBJECTIVES: Surveillance drug resistance mutations (SDRMs) in drug-naive patients are typically used to survey HIV-1-transmitted drug resistance (TDR). We test here how SDRMs in patients failing treatment, the original source of TDR, contribute to assessing TDR, transmissibility and transmission source of SDRMs. DESIGN: This is a retrospective observational study analyzing a Portuguese cohort of HIV-1-infected patients. METHODS: The prevalence of SDRMs to protease inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) in drug-naive and treatment-failing patients was measured for 3554 HIV-1 subtype B patients. Transmission ratio (prevalence in drug-naive/prevalence in treatment-failing patients), average viral load and robust linear regression with outlier detection (prevalence in drug-naive versus in treatment-failing patients) were analyzed and used to interpret transmissibility. RESULTS: Prevalence of SDRMs in drug-naive and treatment-failing patients were linearly correlated, but some SDRMs were classified as outliers - above (PRO: D30N, N88D/S, L90 M, RT: G190A/S/E) or below (RT: M184I/V) expectations. The normalized regression slope was 0.073 for protease inhibitors, 0.084 for NRTIs and 0.116 for NNRTIs. Differences between SDRMs transmission ratios were not associated with differences in viral loads. CONCLUSION: The significant linear correlation between prevalence of SDRMs in drug-naive and in treatment-failing patients indicates that the prevalence in treatment-failing patients can be useful to predict levels of TDR. The slope is a cohort-dependent estimate of rate of TDR per drug class and outlier detection reveals comparative persistence of SDRMs. Outlier SDRMs with higher transmissibility are more persistent and more likely to have been acquired from drug-naive patients. Those with lower transmissibility have faster reversion dynamics after transmission and are associated with acquisition from treatment-failing patients.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationAIDS. 2015 Sep 24;29(15):2045-52. doi: 10.1097/QAD.0000000000000811.pt_PT
dc.identifier.doi10.1097/QAD.0000000000000811pt_PT
dc.identifier.issn0269-9370
dc.identifier.urihttp://hdl.handle.net/10400.26/18393
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherWolters Kluwerpt_PT
dc.relationCOMPARATIVE STUDY OF THE SELECTIVE PRESSURE, REPLICATION AND TRANSMISSION DYNAMICS OF HIV-1 SUBTYPES
dc.relation.publisherversionhttp://journals.lww.com/aidsonline/fulltext/2015/09240/Assessing_transmissibility_of_HIV_1_drug.17.aspxpt_PT
dc.subjectantiretroviral therapypt_PT
dc.subjectHIV drug resistancept_PT
dc.subjectmutationpt_PT
dc.subjectprotease inhibitorspt_PT
dc.subjectreverse transcriptase inhibitorspt_PT
dc.subjecttransmissionpt_PT
dc.titleAssessing transmissibility of HIV-1 drug resistance mutations from treated and from drug-naive individualspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleCOMPARATIVE STUDY OF THE SELECTIVE PRESSURE, REPLICATION AND TRANSMISSION DYNAMICS OF HIV-1 SUBTYPES
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBPD%2F65605%2F2009/PT
oaire.citation.endPage2052pt_PT
oaire.citation.startPage2045pt_PT
oaire.citation.titleAIDSpt_PT
oaire.citation.volume29(15)pt_PT
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.embargofctPolítica de copyright do editorpt_PT
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublicationc2753b74-84f5-4bc2-b6c7-e02952e0809a
relation.isProjectOfPublication.latestForDiscoveryc2753b74-84f5-4bc2-b6c7-e02952e0809a

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