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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

2016-05Journal article Open access
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dc.contributor.authorTheys, Kristof
dc.contributor.authorLaethem, Kristel Van
dc.contributor.authorGomes, Perpétua
dc.contributor.authorBaele, Guy
dc.contributor.authorPineda-Peña, Andrea-Clemencia
dc.contributor.authorVandamme, Anne-Mieke
dc.contributor.authorCamacho, Ricardo J.
dc.contributor.authorAbecasis, Ana B.
dc.contributor.authoron behalf of the Portuguese HIV-1 Resistance Study Group
dc.date.accessioned2016-09-28T09:02:47Z
dc.date.available2016-09-28T09:02:47Z
dc.date.issued2016-05
dc.descriptionThis Open Access article is distributed under the terms of the Creative Commons Attribution Noncommercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.pt_PT
dc.description.abstract"Objective: 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."pt_PT
dc.identifier.citationTheys Kristof, Van Laethem Kristel, Gomes Perpetua, Baele Guy, Pineda-Peña Andrea-Clemencia, Vandamme Anne-Mieke, Camacho Ricardo J., Abecasis Ana B., and on behalf of the Portuguese HIV-1 Resistance Study Group. AIDS Research and Human Retroviruses. April 2016, 32(5): 427-433. doi:10.1089/aid.2015.0095.pt_PT
dc.identifier.doi10.1089/aid.2015.0095pt_PT
dc.identifier.issn0889-2229
dc.identifier.issn1931-8405
dc.identifier.urihttp://hdl.handle.net/10400.26/14892
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMary Ann Liebert, Inc.pt_PT
dc.relationPreparedness, Prediction and Prevention of Emerging Zoonotic Viruses with Pandemic Potential using Multidisciplinary Approaches
dc.relationEvolutionary reconstruction of viral spread in time and space
dc.relationHarmonizing, Integrating and Vitalizing European Research on hiv/Aids
dc.relation.publisherversionhttp://online.liebertpub.com/doi/10.1089/aid.2015.0095pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/pt_PT
dc.subjectNonnucleoside reverse transcriptase inhibitorpt_PT
dc.subjectRilpivirinept_PT
dc.subjectHIV-1pt_PT
dc.subjectAntiretroviral therapypt_PT
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 mutationspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitlePreparedness, Prediction and Prevention of Emerging Zoonotic Viruses with Pandemic Potential using Multidisciplinary Approaches
oaire.awardTitleEvolutionary reconstruction of viral spread in time and space
oaire.awardTitleHarmonizing, Integrating and Vitalizing European Research on hiv/Aids
oaire.awardURIinfo:eu-repo/grantAgreement/EC/FP7/278433/EU
oaire.awardURIinfo:eu-repo/grantAgreement/EC/FP7/260864/EU
oaire.awardURIinfo:eu-repo/grantAgreement/EC/FP7/249697/EU
oaire.citation.endPage433pt_PT
oaire.citation.startPage427pt_PT
oaire.citation.titleAIDS Research and Human Retrovirusespt_PT
oaire.citation.volume32(5)pt_PT
oaire.fundingStreamFP7
oaire.fundingStreamFP7
oaire.fundingStreamFP7
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.nameEuropean Commission
project.funder.nameEuropean Commission
project.funder.nameEuropean Commission
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublication9cb52008-5e4b-4cea-bf53-d8fab748c48b
relation.isProjectOfPublicationef30000f-b69c-4ae9-bf9e-7f7b2452244b
relation.isProjectOfPublication2038a56e-5ce4-453c-bfd6-a33cb26860eb
relation.isProjectOfPublication.latestForDiscoveryef30000f-b69c-4ae9-bf9e-7f7b2452244b

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