Development of an oral once-weekly drug delivery system for HIV antiretroviral therapy

Development of an oral once-weekly drug delivery system for HIV antiretroviral therapy


One of the major advances in the treatment of HIV infection has been the introduction of antiretroviral therapy Antiretrovirals have an incredible capacity to reduce HIV related deaths when patients take the medication regularly Antiretrovirals are also used in those who are at risk of exposure to HIV for prevention often referred to as pre exposure prophylaxis Or PrEP when subjects take anti retrovirals They’re able to protect themselves against HIV infection as demonstrated in several clinical trials One of the major challenges though is that these medications need to be taken daily? Studies have consistently shown that 20% to 30% of medication prescriptions are never filled and that Approximately 50% of medications for chronic disease are not taken as prescribed in different studies conducted all over the world many Individuals do not manage to take their medication on a regular basis and often subjects are found to have drug levels in their blood Which are much lower than expected if they were taking their pills as prescribed? Several research groups around the world are trying to tackle this problem by developing implants like vaginal rings that can release drugs slowly Over prolonged time periods or long lasting injectable drugs we decided to take a completely different approach Since swallowing pills is so much easier than getting an injection or implant Our goal has been to develop a new type of pill that would dramatically reduce how often someone needs to take their HIV drugs you can’t change the patient But you can change the drug delivery system We started by transforming the capsule to maximum Ease and dosing we have developed a capsule in the form of a star with six arms Each arm can be loaded with a different formulation or even a different drug and provide extended drug coverage or drug release we optimized the System to reside in the stomach and remain stable for at least a week We then identified a set of anti retrovirals that are potent enough to work with our system these include dolutegravir, rilpiverene and cabotegravir We developed novel formulations of these three drugs and demonstrated the ability to release them over the course of seven days initially in vitro and then in vivo in a pig animal model This system is also demonstrated to be quite safe to remain in the stomach for long durations To understand the potential real-world impacts of this system we collaborated with the Institute for disease modeling and the program for Evolutionary dynamics at Harvard we conducted a meta-analysis to understand the impact of decreasing the frequency of drug Administration on the efficacy of PrEP we predict a 20% increase in efficacy if prep were available in a weekly formulation using this finding and data from multiple large clinical trials looking at Non-compliance in HIV we evaluated the implementation of this system in South Africa and there alone this system could prevent a potential 200,000 to 800,000 cases of HIV over the next 20 years, our models also showed that in several instances orally administered ultra-long release of anti retrovirals can provide superior coverage compared with standard daily administration We would like to thank the sponsors of this work including the Bill and Melinda Gates Foundation, the National Institutes of Health the division of Gastroenterology at Brigham and Women’s Hospital Bill and Melinda Gates through the Global Good Fund we would also like to thank the tremendous efforts of our collaborators from the program for evolutionary dynamics at Harvard University The Institute for Disease modelling and the general support and feedback from members of the Langer and Traverso laboratories

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