Evidence map›Paper›PMID 36418671›Full record

ArticlePharmaceutical research2023

Preclinical Considerations for Long-acting Delivery of Tenofovir Alafenamide from Subdermal Implants for HIV Pre-exposure Prophylaxis.

Manjula Gunawardana, Mariana Remedios-Chan, Debbie Sanchez, Rob Fanter, Simon Webster, Paul Webster, John A Moss, MyMy Trinh, Martin Beliveau, Christina M Ramirez and 4 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Pharmaceutical research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.4field-weighted citation impact, top 39% 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

3 citing papers in PubMed, 5 citations in OpenAlex.

  1. Trial
  2. Review
  3. Review
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 5 institutions in 1 country.

Manjula GunawardanaDepartment of Chemistry, Oak Crest Institute of Science, 128-132 W. Chestnut Ave., Monrovia, CA, USA.
Mariana Remedios-ChanDepartment of Chemistry, Oak Crest Institute of Science, 128-132 W. Chestnut Ave., Monrovia, CA, USA.
Debbie SanchezDepartment of Chemistry, Oak Crest Institute of Science, 128-132 W. Chestnut Ave., Monrovia, CA, USA.
Rob FanterDepartment of Chemistry, Oak Crest Institute of Science, 128-132 W. Chestnut Ave., Monrovia, CA, USA.
Simon WebsterDepartment of Chemistry, Oak Crest Institute of Science, 128-132 W. Chestnut Ave., Monrovia, CA, USA.
Paul WebsterDepartment of Chemistry, Oak Crest Institute of Science, 128-132 W. Chestnut Ave., Monrovia, CA, USA.
John A MossDepartment of Chemistry, Oak Crest Institute of Science, 128-132 W. Chestnut Ave., Monrovia, CA, USA.
MyMy TrinhCertara USA, Inc., Integrated Drug Development, 100 Overlook Center, Suite 101, Princeton, NJ, USA.
Martin BeliveauCertara USA, Inc., Integrated Drug Development, 100 Overlook Center, Suite 101, Princeton, NJ, USA.
Christina M RamirezDepartment of Biostatistics, UCLA Fielding School of Public Health, University of California, Los Angeles (UCLA), 650 Charles E. Young Drive, Los Angeles, CA, USA.
Mark A MarzinkeDepartment of Medicine, Johns Hopkins University, 600 N. Wolfe Street, Baltimore, MD, USA.
Joseph KuoDepartment of Immunology & Microbiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, USA.
Philippe A GallayDepartment of Immunology & Microbiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, USA.
Marc M BaumDepartment of Chemistry, Oak Crest Institute of Science, 128-132 W. Chestnut Ave., Monrovia, CA, USA. m.baum@oak-crest.org.
Oak Crest Institute of Science · USCertara (United States) · USScripps Research Institute · USJohns Hopkins University · USUniversity of California, Los Angeles · US

Funding

UCLA Rapid, Relevant, Rigorous Implementation Science HubP30MH058107 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Sung-Jae Lee · 1997 to 2026
$53.5M
Systemic Sustained Release Delivery of Antiretroviral Agents for HIV PreventionR01AI162151 · NIAID · OAK CREST INSTITUTE OF SCIENCE · PI BAUM, MARC MICHAEL · 2021 to 2025
$4.3M
Systemic Sustained Release Delivery of Antiretroviral Agents for HIV PreventionR01AI120748 · NIAID · OAK CREST INSTITUTE OF SCIENCE · PI BAUM, MARC MICHAEL · 2015 to 2019
$4.2M
NIAID NIH HHS R01 AI120748NIAID NIH HHS R01 AI162151NIMH NIH HHS P30 MH058107
6 · The paper itself

Abstract

purposeLong-acting formulations of the potent antiretroviral prodrug tenofovir alafenamide (TAF) hold potential as biomedical HIV prevention modalities. Here, we present a rigorous comparison of three animal models, C57BL/6 J mice, beagle dogs, and merino sheep for evaluating TAF implant pharmacokinetics (PKs).

methodsImplants delivering TAF over a wide range of controlled release rates were tested in vitro and in mice and dogs. Our existing PK model, supported by an intravenous (IV) dosing dog study, was adapted to analyze mechanistic aspects underlying implant TAF delivery.

resultsTAF in vitro release in the 0.13 to 9.8 mg d

conclusionsBased on the current results, we recommend using mice and sheep, with macaques as a complementary species, for preclinical TAF implant evaluation with the caveat that our observations may be specific to the implant technology used here. Our report provides fundamental, translatable insights into multispecies TAF delivery via long-acting implants.

Indexed as

Anti-HIV AgentsHIV InfectionsPre-Exposure ProphylaxisAdenineAlanineAnimalsDogsMiceMice, Inbred C57BLSheepTenofovirAdenineAlanineAnti-HIV AgentsTenofovircomparative animal modelsHIV pre-exposure prophylaxisreservoir subdermal implanttenofovir alafenamide

Identifiers

PMID36418671
PMCPMC10421770
OpenAlexW4309924950

What OpenQuestion 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 OpenQuestion graph.