Imperial College London
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DrCarolinaHerrera

Faculty of Medicine, Department of Infectious Disease

Honorary Senior Research Fellow
 
 
 
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Contact

 

carolina.herrera

 
 
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Location

 

460 (Shattock Group)Medical SchoolSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Laura:2022:10.3390/pharmaceutics14061285,
author = {Laura, E and Pillay, A-DAP and Seiphetlo, TB and Lebina, L and Callebaut, C and Minhas, S and Morley, R and Rashid, T and Martinson, N and Fox, J and Khoo, S and Herrera, C},
doi = {10.3390/pharmaceutics14061285},
journal = {Pharmaceutics},
pages = {1--13},
title = {Pre-clinical evaluation of tenofovir and tenofovir alafenamide for HIV-1 pre-exposure prophylaxis in foreskin tissue},
url = {http://dx.doi.org/10.3390/pharmaceutics14061285},
volume = {14},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background: HIV-1 pre-exposure prophylaxis (PrEP) has focused predominantly on the protective efficacy in receptive sex, with limited research on dosing requirements for insertive sex.We pre-clinically assessed the ex vivo pharmacokinetic/pharmacodynamic (PK/PD) profile oftenofovir (TFV) and tenofovir alafenamide (TAF) in foreskin tissue. Methods: Inner and outer fore-skin explants were exposed to serial dilutions of TFV or TAF prior to addition of HIV-1BaL at a high(HVT) or a low viral titer (LVT). Infection was assessed by measurement of p24 in foreskin culturesupernatants. TFV, TAF and TFV-diphosphate (TFV-DP) concentrations were measured in tissue,culture supernatants, dosing and washing solutions. Results: Dose-response curves were obtainedfor both drugs with greater potency observed against LVT. Inhibitory equivalency mimicking oraldosing was defined between 1 mg/mL of TFV and 15 µg/mL of TAF against HVT challenge. Concentrations of TFV-DP in foreskin explants were approximately 6-fold higher after ex vivo dosingwith TAF than with TFV. Statistically significant negative linear correlations were observed between explant levels of TFV or TFV-DP and p24 concentrations following HVT. Conclusions: Pre-clinical evaluation of TAF in foreskin explants revealed greater potency than TFV against penileHIV transmission. Clinical evaluation is underway to support this finding.
AU  - Laura,E
AU  - Pillay,A-DAP
AU  - Seiphetlo,TB
AU  - Lebina,L
AU  - Callebaut,C
AU  - Minhas,S
AU  - Morley,R
AU  - Rashid,T
AU  - Martinson,N
AU  - Fox,J
AU  - Khoo,S
AU  - Herrera,C
DO  - 10.3390/pharmaceutics14061285
EP  - 13
PY  - 2022///
SN  - 1999-4923
SP  - 1
TI  - Pre-clinical evaluation of tenofovir and tenofovir alafenamide for HIV-1 pre-exposure prophylaxis in foreskin tissue
T2  - Pharmaceutics
UR  - http://dx.doi.org/10.3390/pharmaceutics14061285
UR  - https://www.mdpi.com/1999-4923/14/6/1285
UR  - http://hdl.handle.net/10044/1/97498
VL  - 14
ER  -
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