Antiretroviral implants for treatment and prevention of HIV infection

Abstract

Purpose of review: Poor adherence to oral antiretroviral formulations remains the major barrier to the success of long-term treatment and prevention strategies. Although a number of approaches have been developed for long-acting parenteral delivery of antiretroviral drugs, subcutaneous implants are a particularly promising technology as they may be able to provide protective drugs concentrations for a year or longer following a single implant. This review addresses the current status of preclinical and clinical development of antiretroviral implants.

Recent findings: Subcutaneous implants have been widely used for hormonal contraception and the treatment of hormonally driven malignancies for more than 3 decades. These implants are economical to manufacture and deliver, but require special procedures for insertion and removal. They are generally well tolerated and can remain in place for as long as 5 years. A small number of investigational implants are under development for the delivery of antiretroviral drugs. The most advanced of these, containing the investigational antiretroviral MK-8591 (4'-ethynyl-2-fluoro-2'-deoxyadenosine), a potent nucleoside analog reverse transcriptase translocation inhibitor that demonstrates particular promise for subcutaneous implantation, is closest to testing in human subjects. Investigational implants containing tenofovir alafenamide and nevirapine have also been developed and tested in animal models.

Summary: Long-acting antiretroviral implants are a promising new technology, but are in very early stages of development. Potential advantages of these systems include more consistent and predictable drug release than intramuscular injections, and the fact that implants can be removed in the case of adverse events or the desire to stop treatment.