Subdermal Implants: The Next Frontier in HIV Prevention?

Device Could Deliver Protection for Up to One Year

Intarcia Therapeutics, Inc.

HIV prevention has changed dramatically within the course of the past ten years. No longer do we consider condoms or abstinence the main forms of HIV protection. Today there is an ever-widening range of strategies that can work together to reduce the risk of HIV to near-negligible levels.

Chief among these has been the advent of pre-exposure prophylaxis (PrEP), a once-daily pill which can reduce HIV risk by as much as 92 percent.

When used with an HIV-positive partner on antiretroviral therapy, the risk can drop even further—to over 99 percent by some estimates.

Yet despite it proven efficacy, there remain major challenges in the implementation of PrEP. In addition to the task of daily drug taking, we’re not even yet sure how much adherence is needed to achieve the full protective benefit. Some studies have suggested that gay and bisexual men may need only two to three doses per week, while women may require near-perfect adherence to achieve similar results.

Developing a tool, therefore, that can provide full-time protection is considered a major priority among scientists and health officials alike.

In January 2017, the Bill and Melinda Gates Foundation laid down the research gauntlet by donating $50 million to Intarcia Therapeutics, a Boston-based biopharmaceutical firm, to develop a device which can be implanted beneath the skin to deliver HIV protection around the clock.

The donation effectively places subdermal implants on the developmental fast track, alongside other long-acting therapies currently being explored for both the prevention and treatment of HIV.

How a Subdermal Implant Would Work

The Intarcia device is not the first such device to use subdermal technologies to deliver a steady dose of preventive medications.

Contraceptive implants, roughly the size of a matchstick, have been used since 1983 to prevent pregnancy in women, with newer devices able to deliver up to three years of continuous protection.

Similar implantable products have been investigated for use in type 2 diabetes, cancer therapy, tuberculosis treatment, and even schizophrenic disordes.

Within the field of HIV, one of the first subdermal implants was developed by the Pasadena-based Oak Crest Institute of Science. Early animal research showed that their device, when implanted beneath the skin of the forearm, was able to deliver a continual dose of tenofovir alafenamide (TAF) for up to 40 days with no apparent side effects.

Research is underway to expand upon those results, with the aim of creating a device able to deliver steady stream coverage for up to 12 months.

While similar in approach, the Intarcia device (called ITCA 650) offers a unique "mini-pump" system that better stabilizes dosing for up to six months. Water from extracellular fluid enters one end of the device through a semi-permeable membrane, which then expands and drives an osmotic piston. The ITCA 650 is seen to be a major advance over previous devices and has already achieved impressive results in human diabetes trials.

If similar results are achieved in HIV, a device could be approved within the span of a few, short years. While Intarcia has yet to decide which antiretroviral drug to employ, most believe that Truvada (already considered the standard for oral PrEP) will be the likely candidate given that its patent is due to expire in 2018.

Why a Subdermal Implant Is So Important

While most people taking oral PrEP are able to maintain high levels of adherence, its use among high-risk groups can vary significantly. According to research presented at the 21st International AIDS Conference in Durban, the individuals at greatest risk of HIV are rarely those who take PrEP.

This includes African Americans, who represent 44 percent of new annual infections but only ten percent of PrEP prescriptions.

While price most certainly plays a role in this disparity, stigma and disclosure also contribute, particularly among gay and bisexual African American men who have a 50 percent lifetime risk of getting HIV. To some of these men, any form of HIV therapy (even preventive therapy) is akin to outright declaration of their sexual orientation.

Given these realities, might an otherwise invisible preventive tool overcome these fears?

It’s a question posed by global health officials, who have long strived to prevent HIV in vulnerable populations, particularly disempowered women and girls. However, many of the proposed strategies, while great on paper, have either failed or fallen well short of expectations. Among them:

  • The VOICE and FEM-PrEP trials, two early PrEP studies that failed to prevent infection in a cohort of African women, due mainly to suboptimal treatment adherence.
     
  • The ASPIRE and RING trials, which provided specially treated intravaginal rings to over 5,000 African women. In both cases, the devices achieved only modest reduction in HIV risk (27 percent and 37 percent, respectively). Moreover, those at highest risk (ages of 18 and 24) had absolutely no protective benefit.

It is against this backdrop that subdermal implants show the greatest promise. Not only should they be able to be produced at a lower price than oral therapies, they allow women and others to protect themselves with minimal detection. And unlike intravaginal rings and other microbicidal products, they cannot be misused or readily removed. (One of the only downsides may be the fact that the implant procedure would need to be performed under a local anesthetic.)

While it will likely be years before any such device is approved for the treatment or prevention of HIV, the early research remain promising. To this end, the Gates Foundation has pledged an additional $90 million in milestone grants to better ensure that the promise of subdermal HIV implants become a reality.

Sources:

Bancroft, a. “Intarcia receives $140m Gate Foundation Grant for needle-free HIV Tech.” in-Pharma Technologist. Published January 4, 2017.

Montanya, J. “Handbook of Incretin-Based Therapies in Type 2 Diabetes.” June 8, 2016; Springer Link; pp. 77-92.

Du Toit, L.; Pillay, V.; and Danckwerts, M. “Tuberculosis Chemotherapy: current drug delivery approaches.” Respir. Res. September 2006; 7(1):118.

Gunawardana, M.; Remedios-Chan, M.; Miller, C.; et al. “Phamokinetics of Long-acting Tenofovir Alafenamide (GS-7340) Subdermal Implants for HIV Prophylaxis.” Antimicrobial Agents and Chemotherapy. April 15, 2015; 4(2):186-190.

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