A Subcutaneous Implant of Tenofovir Alafenamide Fumarate Causes Local Inflammation and Tissue Necrosis in Rabbits and Macaques-Reference-Cited by-同舟云学术

A Subcutaneous Implant of Tenofovir Alafenamide Fumarate Causes Local Inflammation and Tissue Necrosis in Rabbits and Macaques

Published:2020-02-21 Issue:3 Volume:64 Page:
ISSN:0066-4804
Container-title:Antimicrobial Agents and Chemotherapy
language:en
Short-container-title:Antimicrob Agents Chemother

Author:

Su Jonathan T.¹²,Simpson Solange M.¹,Sung Samuel¹,Tfaily Ewa Bryndza³,Veazey Ronald⁴,Marzinke Mark⁵,Qiu Jiang¹,Watrous David¹,Widanapathirana Lakmini¹,Pearson Elizabeth¹,Peet M. Melissa⁶,Karunakaran Dipu¹,Grasperge Brooke⁴,Dobek Georgina⁷,Cain Charlette M.⁸,Hope Thomas³^ORCID,Kiser Patrick F.¹^ORCID

Affiliation:

1. Department of Biomedical Engineering, Northwestern University, Evanston, Illinois, USA

2. Department of Physics and Engineering, Elon University, Elon, North Carolina, USA

3. Department of Cell and Molecular Biology, Northwestern University, Chicago, Illinois, USA

4. Division of Comparative Pathology, Tulane National Primate Research Center, Covington, Louisiana, USA

5. Division of Clinical Pharmacology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

6. CONRAD, Contraceptive Research and Development, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Arlington, Virginia, USA

7. Tulane University School of Medicine, New Orleans, Louisiana, USA

8. Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA

Abstract

We describe the in vitro and in vivo evaluation of a subcutaneous reservoir implant delivering tenofovir alafenamide hemifumarate (TAF) for the prevention of HIV infection. These long-acting reservoir implants were able to deliver antiretroviral drug for over 90 days in vitro and in vivo . We evaluated the implants for implantation site histopathology and pharmacokinetics in plasma and tissues for up to 12 weeks in New Zealand White rabbit and rhesus macaque models.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Link

https://journals.asm.org/doi/pdf/10.1128/AAC.01893-19

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