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In Vitro Study of PrEP Implants Demonstrates Sustained Release of TAF

JUL 16, 2019 | JONNA LORENZ
Research is advancing to provide alternative delivery systems for HIV pre-exposure prophylaxis (PrEP), including subcutaneous implants that could help improve adherence.

A new article, published in the journal Pharmaceutics, details the characteristics of long-acting (LA) reservoir-style implants that have undergone in vitro studies, demonstrating sustained release of tenofovir alafenamide (TAF) at a dose of 0.28 ± 0.06 mg/day for 180 days.

“A promising biomedical approach for LA-PrEP involves implants that reside under the skin to continuously release the drug, which supports adherence over longer time periods, enables discretion of use, lowers the burden of the regimen, and remains reversible during the therapeutic duration,” the article noted.

Investigators at nonprofit research institute RTI International fabricated an implant using a biodegradable polymer, poly(ε-caprolactone) (PCL), that demonstrated release of TAF between 0.91 and 0.15 mg/day, which was affected by surface area of the implant, the thickness of the PCL tube walls, and the properties of the PCL.

“These data indicate that PCL is an ideal polymer suited for membrane-controlled drug diffusion applications given its material properties and semi-crystalline nature,” the article noted.

The material allows for drug diffusion while the crystals provide structural integrity and modulate drug diffusion, allowing for sustained release.

Investigators used wall thickness to tune the release of TAF between 0.91 ± 0.23 mg/day (45 µm wall thickness) and 0.15 ± 0.03 mg/day (200 µm wall thickness).

The study also showed promise for developing extruded tubes with thicker walls that are more easily handled. The implants also are compatible with contraceptive trocars.

“Although outside the scope of this manuscript, additional strategies to further increase drug stability, dosing, and duration from a single implant, while simultaneously maintaining compatibility with market-available trocars, include modifications to the formulations such as selection and quantity of excipient,” the article reported.

Investigators used two types of PCL—PC-12 and Sigma-PCL—and recorded slight differences in the mass percent of crystallinity and crystalline sizes that affect release rates.

“Overall, this implantable drug delivery system holds various parameters that can be tuned to achieve a targeted dose of TAF,” the study authors noted. “Although the final design of this drug delivery system for TAF awaits feedback from dosing requirements, these promising results help to highlight the path towards the goal of developing LA delivery of TAF for HIV PrEP.”

Funding for the research was from the Bill & Melinda Gates Foundation and the United States Agency for International Development through the US President’s Emergency Plan for AIDS Relief.

Study author Leah M. Johnson, PhD, a research chemist at RTI International, wrote about efforts to develop an implant for PrEP delivery in an article last year in Contagion®. The article, which was co-authored by Ariane Van Der Straten, PhD, MPH, a senior fellow and the director of the Women’s Global Health Imperative Program at RTI International and a professor of medicine at University of California, San Francisco, explained that no single delivery method is ideal for everyone.

“Ideally, the future of HIV PrEP will entail widespread availability of different products to afford individuals the choice to protect themselves against HIV in a manner conducive to lifestyle, circumstances, and perceived risk factors,” the article concluded.

Alternative delivery methods could help address suboptimal retention in care among patients who initiate PrEP. One study in Rhode Island, Mississippi, and Missouri found that retention dropped to 72% at 3 months and 57% at 6 months.

An in silico simulation study presented earlier this year at the Annual Conference on Retroviruses and Opportunistic Infections (CROI 2019) found that subcutaneous implants of long-acting TAF could provide protective levels for more than 6 months.
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