Researchers Develop Slow-Release Pill to Increase HIV Treatment Adherence

Using an “ingestible mini pill box,” researchers have developed a slow-release pill to deliver HIV treatment, according to a press release from researchers at Brigham and Women’s Hospital.

While antiretroviral therapy (ART) has significantly improved disease management for people with HIV and provided an effective prevention strategy for non-infected individuals at high risk for infection, adherence to the medication has proven to be a challenge. Adherence levels can be attributed to several factors, such as access to affordable medication, stigma about disease status, and side effects of ART, according to the researchers, whose work was published in Nature Communications. In particular, the burden of taking the pill daily has deterred adherence.

“We reasoned that a technology that reduces dosing frequency and is administered orally could be a promising alternative for addressing imperfect adherence to ART,” wrote the researchers. “However, development of such a system has previously proven difficult due to the limited residence of drugs in the gastrointestinal tract.”

The team built upon a capsule design that they originally developed in 2016. The capsule, once inside the stomach, unfolds into a 6-armed structure. The structure is too large to pass through the pylorus, while allowing food to continue passing through the digestive system. The arms provided rigidity, and the capsule-contained polymers and other materials to allow the drug to diffuse out slowly over time, according to the researchers.

Now, the capsule can accommodate multiple drugs at a time, holding 1 in each of its arms. The research team assessed the delivery of the antiretrovirals dolutegravir, rilpivirine, and cabotegravir for HIV prevention for non-infected patients and viral suppression for those infected. The concentration profiles for each of the doses over time were tested, and the presence of each drug in the bloodstream in the week following ingestion were measured.

According to the release, the researchers applied mathematical modeling to predict what happens with extended drug release systems when a patient misses a dose and determine what could be done to improve prevention strategy.

Using simulations of viral dynamics and adherence patterns, the researchers predict that this system could not only reduce therapeutic failures, but also prevent thousands of new HIV cases.

“Specifically, conversion from a daily to weekly dose could improve the efficacy of pre-exposure HIV prevention strategies by up to 20%,” said the press release. “Models of populations in South Africa showed that implementing the new dosage form had the potential to prevent 200,000 to 800,000 new infections over the next 20 years.”

The research team is currently working to scale up and validate the results from preclinical models in order to deliver the potential therapy to patients.