摘要：SummaryNon-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 onex vivoARV 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.Graphical abstractDisplay OmittedHighlights•Tenofovir-maraviroc combinations show greater potency in NHP than in human tissue•Opposite drug distribution in mucosal tissues was observed between both species•Greater loss of viral replication fitness with RT mutations for SIV than for HIV-1•Ex vivotissue models are a bridge between NHP studies and human clinical trialsNatural sciences; Biological sciences; Toxicology; Immunology; Biological sciences research methodologies
