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.