Design and Testing of a Cabotegravir Implant for HIV Prevention.
Dipu Karunakaran, Solange M Simpson, Jonathan T Su, Ewa Bryndza-Tfaily, Thomas J Hope, Ronald Veazey, Georgina Dobek, Jiang Qiu, David Watrous, Samuel Sung, Jorge E Chacon, Patrick F Kiser
Author Information
Dipu Karunakaran: Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA.
Solange M Simpson: Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA.
Jonathan T Su: Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA; Department of Physics and Engineering, Elon University, Elon, NC, USA.
Ewa Bryndza-Tfaily: Department of Cell and Developmental Biology, Northwestern University, Chicago, IL, USA.
Thomas J Hope: Department of Cell and Developmental Biology, Northwestern University, Chicago, IL, USA.
Ronald Veazey: Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA, USA.
Georgina Dobek: Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA, USA; Tulane University School of Medicine, New Orleans, LA, USA.
Jiang Qiu: Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA.
David Watrous: Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA.
Samuel Sung: Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA.
Jorge E Chacon: Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA.
Patrick F Kiser: Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA. Electronic address: patrick.kiser@northwestern.edu.
Long-acting antiretroviral implants could help protect high-risk individuals from HIV infection. We describe the design and testing of a long-acting reservoir subcutaneous implant capable of releasing cabotegravir for several months. We compressed cabotegravir and excipients into cylindrical pellets and heat-sealed them in tubing composed of hydrophilic poly(ether-urethane) -. The implants have a 47 mm lumen length, 3.6 mm outer diameter, and 200 μm wall thickness. Four cabotegravir pellets were sealed in the membrane, with a total drug loading of 274 ± 3 mg. In vivo, the implants released 348 ± 107 μg/day (median value per implant, N = 41) of cabotegravir in rhesus macaques. Five implants generated an average cabotegravir plasma concentration of 373 ng/ml in rhesus macaques. The non-human primates tolerated the implant without gross pathology or microscopic signs of histopathology compared to placebo implants. Cabotegravir plasma levels in macaques dropped below detectable levels within two weeks after the removal of the implants.
