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 longacting 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.

A qualitative assessment in acceptability and barriers to use pre-exposure prophylaxis (PrEP) among men who have sex with men: implications for service delivery in Vietnam

“…In addition to oral pills, innovative strategies such as bi-monthly long-acting injectable PrEP (e.g., cabotegravir and rilpivirine) and rectal microbicide gel have been proven in recent years [22][23][24]. Other potential long-active PrEP candidates included a once-monthly oral pill from Merck, bi-annually long-acting injectable PrEP from Gilead, and slow release/long-acting implants such as Islatravir [25]. Longactive PrEP would be beneficial to ease adherence, while a microbicide gel could be used when having sexual intercourse in combination with a condom [14,26,27].…”

Long‐acting and extended‐release implant and nanoformulations with a synergistic antiretroviral two‐drug combination controls HIV‐1 infection in a humanized mouse model

“…35 Therefore a number of recent research efforts have focused on longacting, extended release formulations summarized in a recent review. 9 Cabenuva has currently been approved by the FDA. 8 Further advances have been reported in preclinical studies with AIDS drugs formulated as long-acting, extended release implants.…”

Pharmacology of HIV Cure: Site of Action

“…107 Drug eluting implants-historically utilized for hormonal contraception-are of particular interest in the HIV treatment and prevention fields for their potential to provide more predictable ARV release for up to 5 years and have been reviewed extensively elsewhere. 108 Specialized formulations designed to extend dosing intervals may also augment ART distribution into tissues via alterations in the chemical makeup of the vehicles in which ART resides (e.g., lipid nanoparticles). 104 For instance, lipid nanoparticles have been formulated that establish precedent that combination ART can be delivered through one administration.…”

“…Islatravir has also been formulated into a subcutaneous, drug‐eluting implant which has been studied in a phase I clinical trial 107 . Drug eluting implants—historically utilized for hormonal contraception—are of particular interest in the HIV treatment and prevention fields for their potential to provide more predictable ARV release for up to 5 years and have been reviewed extensively elsewhere 108 …”