In the fight against the HIV epidemic, medication non-adherence 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 today, researchers from Brigham and Women's Hospital, Massachusetts Institute of Technology and their collaborators describe a "mini pill box," 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, MB, BChir, PhD, a gastroenterologist and biomedical engineer in the Division of Gastroenterology at BWH and an Assistant Professor of Medicine at Harvard Medical School.
The team built on a design they had developed in 2016 of a capsule that, once inside the stomach, unfolds into a star-shaped structure too large to pass through the pylorus--the connection between the stomach and the small intestine--and exit the stomach, yet designed to allow 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.
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 non-infected 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.
This work was funded in part by the Bill and Melinda Gates Foundation Grants No. OPP1139937, OPP1139921 and OPP1148627, NIH Grants No. EB-000244, R01AI131416 and DP5OD019851. G. Traverso was supported in part by the Division of Gastroenterology, Brigham and Women's Hospital. C. Selinger, A. Bershteyn and P. A. Eckhoff are supported by Bill and Melinda Gates through the Global Good Fund.
Paper Cited: Kirtane and Abouzid et. al "Development of an oral once-weekly drug delivery system for HIV antiretroviral therapy" DOI: 10.1038/s41467-017-02294-6
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