Design and Testing of a Cabotegravir Implant for HIV Prevention

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 mu m 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 mu g/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.

Automated summary

The study introduces a long-acting antiretroviral implant designed to release cabotegravir for several months, aiming to protect high-risk individuals from HIV infection. In vivo experiments in rhesus macaques demonstrated that the implant could steadily release cabotegravir and quickly reduce plasma levels to undetectable levels after removal. The findings suggest that this implant has potential for HIV prevention in high-risk populations.