Else, Laura, Penchala, Sujan D, Pillay, Azure-Dee, Seiphetlo, Thabiso B, Lebina, Limakatso, Callebaut, Christian, Minhas, Suks, Morley, Roland, Rashid, Tina, Martinson, Neil et al (show 3 more authors)
(2022)
Pre-Clinical Evaluation of Tenofovir and Tenofovir Alafenamide for HIV-1 Pre-Exposure Prophylaxis in Foreskin Tissue
PHARMACEUTICS, 14 (6).
1285-.
ISSN 1999-4923, 1999-4923
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Pre-Clinical Evaluation of Tenofovir and Tenofovir Alafenamide for HIV-1 Pre-Exposure Prophylaxis in Foreskin Tissue.pdf - Published version Download (3MB) | Preview |
Abstract
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-1<inf>BaL</inf> 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HIV-1, foreskin, pre-exposure prophylaxis |
| Divisions: | Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Systems, Molec & Integrative Biology > Inst. Systems, Molec & Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 28 Oct 2022 14:58 |
| Last Modified: | 16 Jun 2026 07:29 |
| DOI: | 10.3390/pharmaceutics14061285 |
| Related Websites: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3165849 |
| Disclaimer: | The University of Liverpool is not responsible for content contained on other websites from links within repository metadata. Please contact us if you notice anything that appears incorrect or inappropriate. |
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