Subcutaneous implants are 1 promising strategy to address suboptimal adherence to pre-exposure prophylaxis (PrEP) for HIV, and a recent in silico simulation examined pharmacokinetic profiles and safety of tenofovir alafenamide implants.
Adherence to pre-exposure prophylaxis (PrEP) for HIV remains a difficult challenge, but subcutaneous implants are 1 promising possibility for addressing the issue.
An in silico simulation study presented at the Annual Conference on Retroviruses and Opportunistic Infections (CROI 2019) found that subcutaneous implants of long-acting tenofovir alafenamide (TAF) could provide protective levels for more than 6 months.
Building on a previously published pharmacokinetic model, the investigation at the University of Liverpool, RTI International, and Johns Hopkins University School of Medicine integrated subcutaneous mechanistic modelling. Simulations conducted on 500 virtual healthy women for 28 days found that TAF implants with release rates at a minimum of 0.6 mg/day sustained above-target concentrations of tenofovir diphosphate.
"A 2.5 mm x 40 mm implant rod, like that of contraceptive implants, containing 120 mg of TAF and delivering at 0.6 mg/day could provide protective levels for over 6 months," investigtors reported in the abstract.
Marc Baum, PhD, senior faculty member at Oak Crest Institute of Science, told Contagion®, "We have successfully developed a technology platform to linearly deliver TAF subcutaneously over a wide range of daily release rates. We have evaluated the implants in mice, dogs, and sheep. The devices are safe at our target release rates and show promise for HIV PrEP."
Baum was an author of the study "Pharmacokinetics of Long-Acting Tenofovir Alafenamide (GS-7340) Subdermal Implant for HIV Prophylaxis" published in 2015 in the American Society for Microbiology journal Antimicrobial Agents and Chemotherapy.
He said the biggest surprise in the research has been the variance in PK across animal species and noted that an exploratory clinical trial in humans is imperative.
"The next couple of years’ research are going to determine whether a TAF subdermal implant of practical physical dimensions is theoretically feasible (from a safety and PK perspective) as a product for HIV PrEP," Baum told Contagion®. "This will need to be confirmed in subsequent clinical trials in terms of efficacy."
The study published in 2015 aimed to develop a sustained-release TAF implant and evaluate the PK and safety in dogs and demonstrated proof of principle.
Diversity in drug delivery is important to optimizing PrEP, according to a study that found that no single product is appealing across different demographics. Strategies include oral pills, topical delivery, inject­ables, and implants. Different implant designs are being studied. The benefits of implants include that it is a gender-neutral approach, it would prevent all modes of exposure, it is discreet, it promotes independence, it is administered by providers and doesn't require users to remember to continually take pills, and it offers protection for a long duration.
Recent studies have revealed 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.