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Sub-Epidemics Explain Localized High Prevalence of Reduced Susceptibility to Rilpivirine in Treatment-Naive HIV-1-Infected Patients: Subtype and Geographic Compartmentalization of Baseline Resistance Mutations

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dc.creatorTheys, Kristofspa
dc.creatorVan Laethem, Kristelspa
dc.creatorGomes, Perpetuaspa
dc.creatorBaele, Guyspa
dc.creatorPineda-Peña, Andrea-Clemenciaspa
dc.creatorVandamme, Anne-Miekespa
dc.creatorCamacho, Ricardo J.spa
dc.creatorAbecasis, Ana B.spa
dc.date.accessioned2020-05-26T00:06:54Z
dc.date.available2020-05-26T00:06:54Z
dc.date.created2016spa
dc.description.abstractObjective: The latest nonnucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine (RPV) is indicated for human immunodeficiency virus type-1 (HIV-1) patients initiating antiretroviral treatment, but the extent of genotypic RPV resistance in treatment-naive patients outside clinical trials is poorly defined. Study Design: This retrospective observational study of clinical data from Belgium and Portugal evaluates genotypic information from HIV-1 drug-naive patients obtained for the purpose of drug resistance testing. Rilpivirine resistance-associated mutations (RPV-RAMs) were defined based on clinical trials, phenotypic studies, and expert-based resistance algorithms. Viral susceptibility to RPV alone and to the single-tablet regimen was estimated using expert-based resistance algorithms. Results: In 4,631 HIV-1 treatment-naive patients infected with diverse HIV-1 subtypes, major RPV-RAMs were detected in 4.6%, while complete viral susceptibility to RPV was estimated in 95% of patients. Subtype C- and F1-infected patients displayed the highest levels of reduced viral susceptibility at baseline, respectively 13.2% and 9.3%, mainly due to subtype- and geographic-dependent occurrence of RPV-RAMs E138A and A98G as natural polymorphisms. Strikingly, a founder effect in Portugal resulted in a 138A prevalence of 13.2% in local subtype C-infected treatment-naive patients. The presence of transmitted drug resistance did not impact our estimates. Conclusion: RPV is the first HIV-1 inhibitor for which, in the absence of transmitted drug resistance, intermediate or high-level genotypic resistance can be detected in treatment-naive patients. The extent of RPV susceptibility in treatment-naive patients differs depending on the HIV-1 subtype and dynamics of local compartmentalized epidemics. The highest prevalence of reduced susceptibility was found to be 15.7% in Portuguese subtype C-infected treatment-naive patients. In this context, even in the absence of transmitted HIV-1 drug resistance (TDR), drug resistance testing at baseline should be considered extremely important before starting treatment with this NNRTI. © Kristof Theys, et al., 2016; Published by Mary Ann Liebert, Inc. 2016.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1089/aid.2015.0095
dc.identifier.issn8892229
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/23941
dc.language.isoengspa
dc.publisherMary Ann Liebert Inc.spa
dc.relation.citationEndPage433
dc.relation.citationIssueNo. 5
dc.relation.citationStartPage427
dc.relation.citationTitleAIDS Research and Human Retroviruses
dc.relation.citationVolumeVol. 32
dc.relation.ispartofAIDS Research and Human Retroviruses, ISSN:8892229, Vol.32, No.5 (2016); pp. 427-433spa
dc.relation.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84966600896&doi=10.1089%2faid.2015.0095&partnerID=40&md5=87acff6e71ef84ce0432cc827b2ba707spa
dc.rights.accesRightsinfo:eu-repo/semantics/openAccess
dc.rights.accesoAbierto (Texto Completo)spa
dc.source.instnameinstname:Universidad del Rosariospa
dc.source.reponamereponame:Repositorio Institucional EdocURspa
dc.subject.keywordRilpivirinespa
dc.subject.keywordAnti human immunodeficiency virus agentspa
dc.subject.keywordRilpivirinespa
dc.subject.keywordRna directed dna polymerase inhibitorspa
dc.subject.keywordAntiviral resistancespa
dc.subject.keywordAntiviral susceptibilityspa
dc.subject.keywordArticlespa
dc.subject.keywordBelgiumspa
dc.subject.keywordEpidemicspa
dc.subject.keywordFounder effectspa
dc.subject.keywordGenotypespa
dc.subject.keywordGeographic distributionspa
dc.subject.keywordHumanspa
dc.subject.keywordHuman immunodeficiency virus 1spa
dc.subject.keywordHuman immunodeficiency virus 1 infectionspa
dc.subject.keywordHuman immunodeficiency virus infected patientspa
dc.subject.keywordMajor clinical studyspa
dc.subject.keywordNonhumanspa
dc.subject.keywordObservational studyspa
dc.subject.keywordPortugalspa
dc.subject.keywordPrevalencespa
dc.subject.keywordPriority journalspa
dc.subject.keywordResistance associated mutationspa
dc.subject.keywordRetrospective studyspa
dc.subject.keywordTabletspa
dc.subject.keywordVirus mutationspa
dc.subject.keywordVirus resistancespa
dc.subject.keywordDrug effectsspa
dc.subject.keywordGeneticsspa
dc.subject.keywordHighly active antiretroviral therapyspa
dc.subject.keywordHiv infectionsspa
dc.subject.keywordMutationspa
dc.subject.keywordProceduresspa
dc.subject.keywordSingle nucleotide polymorphismspa
dc.subject.keywordAnti-hiv agentsspa
dc.subject.keywordAntiretroviral therapyeng
dc.subject.keywordBelgiumspa
dc.subject.keywordDrug resistanceeng
dc.subject.keywordFounder effectspa
dc.subject.keywordGenotypespa
dc.subject.keywordHiv infectionsspa
dc.subject.keywordHiv-1spa
dc.subject.keywordHumansspa
dc.subject.keywordMutationspa
dc.subject.keywordPolymorphismeng
dc.subject.keywordPortugalspa
dc.subject.keywordRetrospective studiesspa
dc.subject.keywordReverse transcriptase inhibitorsspa
dc.subject.keywordRilpivirinespa
dc.titleSub-Epidemics Explain Localized High Prevalence of Reduced Susceptibility to Rilpivirine in Treatment-Naive HIV-1-Infected Patients: Subtype and Geographic Compartmentalization of Baseline Resistance Mutationsspa
dc.typearticleeng
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersion
dc.type.spaArtículospa
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