In the fight against HIV, medication nonadherence remains a major challenge. Although combination therapies have been successful in managing the disease and can be taken to help prevent its spread, research shows that many patients do not stick to these regimens.
Studies have found that in HIV clinical trials, only about 30 percent of patients stick to their dosage plans, which makes it difficult to gather accurate data.
In a new study published in Nature Communications researchers from Harvard Medical School, Brigham and Women’s Hospital, MIT and their collaborators describe a “mini pillbox,” developed in preclinical models, that stays in the stomach to deliver a once-weekly, long-lasting dose of medications to combat HIV.
“These slow-release dosage systems perform equal or better than the current daily doses for HIV treatment in preclinical models,” said C. Giovanni Traverso, HMS assistant professor of medicine and a gastroenterologist and biomedical engineer in the Division of Gastroenterology at Brigham and Women’s.
The team built on a design they developed in 2016 of a capsule that, once inside the stomach, unfolds into a star-shaped structure too large to exit the stomach through the pylorus—the connection between the stomach and the small intestine—while allowing food to continue to pass through the digestive system. The arms of the star provided rigidity, and the capsule contained polymers and other materials to allow the drug to diffuse out slowly over time.
The newly designed pill can hold multiple drugs at one time, accommodating a different medication on each of its six arms. The team investigated delivering the antiretrovirals dolutegravir, rilpivirine and cabotegravir for HIV prevention among noninfected patients and for viral suppression among those infected. Researchers tested the concentration profiles for each of the doses over time in a pig model and measured the presence of each drug in the bloodstream in the week following ingestion.
Additionally, the team applied mathematical modeling to predict what happens with these extended drug-release systems when a patient misses a dose, and what can be done to improve prevention strategy. Simulations of viral dynamics and patient adherence patterns showed that this new 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 percent, the analysis showed. 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 team is now working to scale up and validate results from preclinical models to translate this potential therapy to patients.