Evidence map›Paper›PMID 35745857›Full record

ArticlePharmaceutics2022

Pre-Clinical Evaluation of Tenofovir and Tenofovir Alafenamide for HIV-1 Pre-Exposure Prophylaxis in Foreskin Tissue.

Laura Else, Sujan D Penchala, Azure-Dee Pillay, Thabiso B Seiphetlo, Limakatso Lebina, Christian Callebaut, Suks Minhas, Roland Morley, Tina Rashid, Neil Martinson and 4 more

Open access · goldAbstract read
In one paragraph

Article in Pharmaceutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.4field-weighted citation impact, top 40% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 4 citations in OpenAlex.

  1. Trial
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 7 institutions in 3 countries.

Laura ElseBioanalytical Facility, Molecular and Clinical Pharmacology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 7BE, UK.
Sujan D PenchalaBioanalytical Facility, Molecular and Clinical Pharmacology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 7BE, UK.
Azure-Dee PillayDivision of Immunology, University of Cape Town, Cape Town 7935, South Africa.
Thabiso B SeiphetloDivision of Immunology, University of Cape Town, Cape Town 7935, South Africa.
Limakatso LebinaPerinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2000, South Africa.ORCID 0000-0001-6825-0573
Christian CallebautGilead Sciences, Foster City, CA 94404, USA.
Suks MinhasImperial College Healthcare NHS Trust, Charing Cross Hospital, London W6 8RF, UK.
Roland MorleyImperial College Healthcare NHS Trust, Charing Cross Hospital, London W6 8RF, UK.
Tina RashidImperial College Healthcare NHS Trust, Charing Cross Hospital, London W6 8RF, UK.
Neil MartinsonPerinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2000, South Africa.
Julie FoxGuys and St. Thomas' NHS Foundation Trust and King's College London, London SE1 9RT, UK.ORCID 0000-0002-0583-8019
Saye KhooBioanalytical Facility, Molecular and Clinical Pharmacology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 7BE, UK.ORCID 0000-0002-2769-0967
Carolina HerreraDepartment of Infectious Diseases, Faculty of Medicine, Imperial College, London W2 1PG, UK.ORCID 0000-0003-3701-752X
CHAPS Consortium
Imperial College Healthcare NHS Trust · GBUniversity of Liverpool · GBUniversity of Cape Town · ZAUniversity of the Witwatersrand · ZAGilead Sciences (United States) · USImperial College London · GBKing's College London · GB

Funding

European & Developing Countries Clinical Trials Partnership RIA2016MC - 1616 - CHAPSGilead Sciences (United Kingdom) CO-UK-120-5494
6 · The paper itself

Abstract

backgroundHIV-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.

methodsInner and outer foreskin explants were exposed to serial dilutions of TFV or TAF prior to addition of HIV-1

resultsDose-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.

conclusionsPre-clinical evaluation of TAF in foreskin explants revealed greater potency than TFV against penile HIV transmission. Clinical evaluation is underway to support this finding.

Indexed as

foreskinHIV-1pre-exposure prophylaxis

Identifiers

PMID35745857
PMCPMC9227286
OpenAlexW4283068551

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.