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dc.contributor.author | Herrera, Carolina | |
dc.contributor.author | Cottrell, Mackenzie L | |
dc.contributor.author | Prybylski, John | |
dc.contributor.author | Kashuba, Angela D M | |
dc.contributor.author | Veazey, Ronald S | |
dc.contributor.author | García-Pérez, Javier | |
dc.contributor.author | Olejniczak, Natalia | |
dc.contributor.author | McCoy, Clare F | |
dc.contributor.author | Ziprin, Paul | |
dc.contributor.author | Richardson-Harman, Nicola | |
dc.contributor.author | Alcamí, José | |
dc.contributor.author | Malcolm, Karl R | |
dc.contributor.author | Shattock, Robin J | |
dc.date.accessioned | 2023-05-04T13:48:12Z | |
dc.date.available | 2023-05-04T13:48:12Z | |
dc.date.issued | 2022-05 | |
dc.identifier.citation | iScienc. 2022 May 16;25(6):104409. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/15974 | |
dc.description.abstract | Non-human primates (NHP) are widely used for the pre-clinical assessment of antiretrovirals (ARVs) for HIV treatment and prevention. However, the utility of these models is questionable given the differences in ARV pharmacology between humans and macaques. Here, we report a model based on ex vivo ARV exposure and the challenge of mucosal tissue explants to define pharmacological differences between NHPs and humans. For colorectal and cervicovaginal explants in both species, high concentrations of tenofovir (TFV) and maraviroc were predictive of anti-viral efficacy. However, their combinations resulted in increased inhibitory potency in NHP when compared to human explants. In NHPs, higher TFV concentrations were measured in colorectal versus cervicovaginal explants (p = 0.042). In humans, this relationship was inverted with lower levels in colorectal tissue (p = 0.027). TFV-resistance caused greater loss of viral fitness for HIV-1 than SIV. This, tissue explants provide an important bridge to refine and appropriately interpret NHP studies. | es_ES |
dc.description.sponsorship | This work was supported by an NIH R21 award AI094515 and by the European Commission’s seventh Framework "Combined Highly Active Retroviral Microbicides" (CHAARM) (242135). This work was partially supported by project PI19CIII/00004 and the Spanish AIDS Research Network (RIS) funded by Instituto de Salud Carlos III and co-funded by European Development Fund (ERDF) "A way to build Europe" (project RD16CIII/0002/0001). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Elsevier | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | Biological sciences | es_ES |
dc.subject | Biological sciences research methodologies | es_ES |
dc.subject | Immunology | es_ES |
dc.subject | Natural sciences | es_ES |
dc.subject | Toxicology | es_ES |
dc.title | The ex vivo pharmacology of HIV-1 antiretrovirals differs between macaques and humans | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 35663021 | es_ES |
dc.format.volume | 25 | es_ES |
dc.format.number | 6 | es_ES |
dc.format.page | 104409 | es_ES |
dc.identifier.doi | 10.1016/j.isci.2022.104409 | es_ES |
dc.contributor.funder | National Institutes of Health (Estados Unidos) | es_ES |
dc.contributor.funder | Unión Europea. Comisión Europea. 7 Programa Marco | es_ES |
dc.contributor.funder | Red de Investigación Cooperativa en Investigación en Sida (España) | es_ES |
dc.contributor.funder | Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) | es_ES |
dc.contributor.funder | Instituto de Salud Carlos III | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 2589-0042 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1016/j.isci.2022.104409 | es_ES |
dc.identifier.journal | iScience | es_ES |
dc.repisalud.centro | ISCIII::Centro Nacional de Microbiología | es_ES |
dc.repisalud.institucion | ISCIII | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/FP7/242135/EU | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.relation.projectFIS | info:fis/Instituto de Salud Carlos III/Programa Estatal de Generación de Conocimiento y Fortalecimiento del Sistema Español de I+D+I/Subprograma Estatal de Generación de Conocimiento/PI19-ISCIII Modalidad Proyectos de Investigacion en Salud Intramurales. (2019)/PI19CIII/00004 | es_ES |
dc.relation.projectFIS | info:eu-repo/grantAgreement/ES/RD16CIII/0002/0001 | es_ES |