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

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 chalk ge of mucosal tissue explants to define pharmacological diffarences 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.

Automated summary

The utility of non-human primates in evaluating antiretroviral drugs for HIV treatment and prevention is questionable due to pharmacological differences between humans and macaques. We developed an ex vivo model using tissue explants to identify differences in drug efficacy between the two species. Our results showed that high concentrations of tenofovir and maraviroc predicted anti-viral efficacy, with greater inhibitory potency observed in macaques compared to humans.