Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/15974
Título
The ex vivo pharmacology of HIV-1 antiretrovirals differs between macaques and humans
Autor(es)
Fecha de publicación
2022-05
Cita
iScienc. 2022 May 16;25(6):104409.
Idioma
Inglés
Tipo de documento
journal article
Resumen
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.
Palabras clave
Biological sciences | Biological sciences research methodologies | Immunology | Natural sciences | Toxicology
Versión en línea
DOI
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- ExVivoPharmacologyHIV-1_2022.pdf
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