iScience | VOL. 25
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The exvivo pharmacology of HIV-1 antiretrovirals differs between macaques and humans.

Publication Date Jun 17, 2022

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 exvivo 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.

Concepts

Non-human Primates Colorectal Explants Tenofovir Antiretrovirals Concentrations Of Maraviroc Tissue Explants Colorectal Tissue Loss Of Fitness Differences In Pharmacology Mucosal Explants

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No potential conflict of interest was reported by the authors. The conception and design of the study, acquisition of data, analysis and interpretatio...

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