Imperial College London
Paul Ziprin

Paul Ziprin

Faculty of Medicine, Department of Surgery & Cancer

Honorary Clinical Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 3312 7635p.ziprin

 
 
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Assistant

 

Ms Caroline Hurley +44 (0)20 3312 2124

 
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Location

 

Queen Elizabeth the Queen Mother Wing (QEQM)St Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Herrera:2022:10.1016/j.isci.2022.104409,
author = {Herrera, C and Cottrell, ML and Prybylski, J and Kashuba, ADM and Veazey, RS and García-Pérez, J and Olejniczak, N and McCoy, CF and Ziprin, P and Richardson-Harman, N and Alcami, J and Malcolm, KR and Shattock, RJ},
doi = {10.1016/j.isci.2022.104409},
journal = {iScience},
title = {The ex vivo pharmacology of HIV-1 antiretrovirals differs between macaques and humans},
url = {http://dx.doi.org/10.1016/j.isci.2022.104409},
volume = {25},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Herrera,C
AU  - Cottrell,ML
AU  - Prybylski,J
AU  - Kashuba,ADM
AU  - Veazey,RS
AU  - García-Pérez,J
AU  - Olejniczak,N
AU  - McCoy,CF
AU  - Ziprin,P
AU  - Richardson-Harman,N
AU  - Alcami,J
AU  - Malcolm,KR
AU  - Shattock,RJ
DO  - 10.1016/j.isci.2022.104409
PY  - 2022///
SN  - 2589-0042
TI  - The ex vivo pharmacology of HIV-1 antiretrovirals differs between macaques and humans
T2  - iScience
UR  - http://dx.doi.org/10.1016/j.isci.2022.104409
UR  - http://hdl.handle.net/10044/1/96839
VL  - 25
ER  -
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