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
<h4>Background</h4>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.<h4>Methods</h4>Inner and outer foreskin explants were exposed to serial dilutions of TFV or TAF prior to addition of HIV-1<sub>BaL</sub> 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.<h4>Results</h4>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.<h4>Conclusions</h4>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 and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 28 Oct 2022 14:58 |
| Last Modified: | 06 Dec 2024 20:23 |
| DOI: | 10.3390/pharmaceutics14061285 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3165849 |
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