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The ex vivo pharmacology of HIV-1 antiretrovirals differs between macaques and humans

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Title: The ex vivo pharmacology of HIV-1 antiretrovirals differs between macaques and humans
Authors: Herrera, C
Cottrell, ML
Prybylski, J
Kashuba, ADM
Veazey, RS
García-Pérez, J
Olejniczak, N
McCoy, CF
Ziprin, P
Richardson-Harman, N
Alcami, J
Malcolm, KR
Shattock, RJ
Item Type: Journal Article
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.
Issue Date: 17-Jun-2022
Date of Acceptance: 11-May-2022
URI: http://hdl.handle.net/10044/1/96839
DOI: 10.1016/j.isci.2022.104409
ISSN: 2589-0042
Publisher: Cell Press
Journal / Book Title: iScience
Volume: 25
Issue: 6
Copyright Statement: © 2022 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Sponsor/Funder: National Institutes of Health
Funder's Grant Number: 5R21AI094515-03
Keywords: Biological sciences
Biological sciences research methodologies
Natural sciences
Publication Status: Published
Article Number: ARTN 104409
Online Publication Date: 2022-05-16
Appears in Collections:Department of Infectious Diseases
Faculty of Medicine

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