Long-acting implants to treat and prevent HIV infection

Abstract

Purpose of review: Subcutaneous implants are a promising technology to enable long-acting parenteral delivery of antiretroviral drugs (ARV) because they may be able to provide protective drugs concentrations for a year or longer following a single implant. The present review covers the current status of preclinical and clinical development of antiretroviral implants.

Recent findings: Over the past three decades, subcutaneous implants have been widely used for long-acting hormonal contraception and the treatment of hormonally-driven malignancies. They are economical and scalable to manufacture, but require special procedures for insertion and removal. They are generally well tolerated, and can remain in place for up to five years. As long-acting delivery of ARV would confer significant advantages, a few investigational implants are under development for the delivery of ARV; most remain at preclinical stages of development. Islatravir, a potent nucleoside analog reverse transcriptase translocation inhibitor that shows particular promise, has entered clinical testing in implant form. Investigational implants containing tenofovir alafenamide and nevirapine, and entecavir (for hepatitis B virus) have been developed and tested in animal models, with varying degrees of success. There is also burgeoning interest in bioerodable implant formulations of established ARVs.

Summary: LARV implants are a promising new technology, but are in early stages of clinical development. Their potential advantages include more consistent and predictable drug release than that provided by intramuscular injections, the possibility of combining several partner drugs into one implant, and the fact that implants can be removed in the case of a desire to stop treatment or the development of adverse events.