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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
dc.creator | Theys, Kristof | spa |
dc.creator | Van Laethem, Kristel | spa |
dc.creator | Gomes, Perpetua | spa |
dc.creator | Baele, Guy | spa |
dc.creator | Pineda-Peña, Andrea-Clemencia | spa |
dc.creator | Vandamme, Anne-Mieke | spa |
dc.creator | Camacho, Ricardo J. | spa |
dc.creator | Abecasis, Ana B. | spa |
dc.date.accessioned | 2020-05-26T00:06:54Z | |
dc.date.available | 2020-05-26T00:06:54Z | |
dc.date.created | 2016 | spa |
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. © Kristof Theys, et al., 2016; Published by Mary Ann Liebert, Inc. 2016. | eng |
dc.format.mimetype | application/pdf | |
dc.identifier.doi | https://doi.org/10.1089/aid.2015.0095 | |
dc.identifier.issn | 8892229 | |
dc.identifier.uri | https://repository.urosario.edu.co/handle/10336/23941 | |
dc.language.iso | eng | spa |
dc.publisher | Mary Ann Liebert Inc. | spa |
dc.relation.citationEndPage | 433 | |
dc.relation.citationIssue | No. 5 | |
dc.relation.citationStartPage | 427 | |
dc.relation.citationTitle | AIDS Research and Human Retroviruses | |
dc.relation.citationVolume | Vol. 32 | |
dc.relation.ispartof | AIDS Research and Human Retroviruses, ISSN:8892229, Vol.32, No.5 (2016); pp. 427-433 | spa |
dc.relation.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84966600896&doi=10.1089%2faid.2015.0095&partnerID=40&md5=87acff6e71ef84ce0432cc827b2ba707 | spa |
dc.rights.accesRights | info:eu-repo/semantics/openAccess | |
dc.rights.acceso | Abierto (Texto Completo) | spa |
dc.source.instname | instname:Universidad del Rosario | spa |
dc.source.reponame | reponame:Repositorio Institucional EdocUR | spa |
dc.subject.keyword | Rilpivirine | spa |
dc.subject.keyword | Anti human immunodeficiency virus agent | spa |
dc.subject.keyword | Rilpivirine | spa |
dc.subject.keyword | Rna directed dna polymerase inhibitor | spa |
dc.subject.keyword | Antiviral resistance | spa |
dc.subject.keyword | Antiviral susceptibility | spa |
dc.subject.keyword | Article | spa |
dc.subject.keyword | Belgium | spa |
dc.subject.keyword | Epidemic | spa |
dc.subject.keyword | Founder effect | spa |
dc.subject.keyword | Genotype | spa |
dc.subject.keyword | Geographic distribution | spa |
dc.subject.keyword | Human | spa |
dc.subject.keyword | Human immunodeficiency virus 1 | spa |
dc.subject.keyword | Human immunodeficiency virus 1 infection | spa |
dc.subject.keyword | Human immunodeficiency virus infected patient | spa |
dc.subject.keyword | Major clinical study | spa |
dc.subject.keyword | Nonhuman | spa |
dc.subject.keyword | Observational study | spa |
dc.subject.keyword | Portugal | spa |
dc.subject.keyword | Prevalence | spa |
dc.subject.keyword | Priority journal | spa |
dc.subject.keyword | Resistance associated mutation | spa |
dc.subject.keyword | Retrospective study | spa |
dc.subject.keyword | Tablet | spa |
dc.subject.keyword | Virus mutation | spa |
dc.subject.keyword | Virus resistance | spa |
dc.subject.keyword | Drug effects | spa |
dc.subject.keyword | Genetics | spa |
dc.subject.keyword | Highly active antiretroviral therapy | spa |
dc.subject.keyword | Hiv infections | spa |
dc.subject.keyword | Mutation | spa |
dc.subject.keyword | Procedures | spa |
dc.subject.keyword | Single nucleotide polymorphism | spa |
dc.subject.keyword | Anti-hiv agents | spa |
dc.subject.keyword | Antiretroviral therapy | eng |
dc.subject.keyword | Belgium | spa |
dc.subject.keyword | Drug resistance | eng |
dc.subject.keyword | Founder effect | spa |
dc.subject.keyword | Genotype | spa |
dc.subject.keyword | Hiv infections | spa |
dc.subject.keyword | Hiv-1 | spa |
dc.subject.keyword | Humans | spa |
dc.subject.keyword | Mutation | spa |
dc.subject.keyword | Polymorphism | eng |
dc.subject.keyword | Portugal | spa |
dc.subject.keyword | Retrospective studies | spa |
dc.subject.keyword | Reverse transcriptase inhibitors | spa |
dc.subject.keyword | Rilpivirine | spa |
dc.title | 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 | spa |
dc.type | article | eng |
dc.type.hasVersion | info:eu-repo/semantics/publishedVersion | |
dc.type.spa | Artículo | spa |