Related Experiment Video
Updated: Sep 6, 2025
Fabrication and Characterization of Griffithsin-modified Fiber Scaffolds for Prevention of Sexually Transmitted Infections
Published on: October 31, 2017
Pre-Clinical Evaluation of Tenofovir and Tenofovir Alafenamide for HIV-1 Pre-Exposure Prophylaxis in Foreskin Tissue
Laura Else1, Sujan D Penchala1, Azure-Dee Pillay2
1Bioanalytical Facility, Molecular and Clinical Pharmacology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 7BE, UK.
Background:
HIV-1 pre-exposure prophylaxis (PrEP) has focused predominantly on protective efficacy in receptive sex, with limited research on the dosing requirements for insertive sex. We pre-clinically assessed the ex vivo pharmacokinetic-pharmacodynamic (PK-PD) profile of tenofovir (TFV) and tenofovir alafenamide (TAF) in foreskin tissue.
Methods:
Inner and outer foreskin 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 culture supernatants. TFV, TAF and TFV-diphosphate (TFV-DP) concentrations were measured in tissues, culture supernatants and dosing and washing solutions.
Results:
Dose-response curves were obtained for both drugs, with greater potency observed against LVT. Inhibitory equivalency mimicking oral dosing 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 six-fold higher after ex vivo dosing with 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 penile HIV transmission. Clinical evaluation is underway to support this finding.
