By Rebecca Bowers

EXECUTIVE SUMMARY

Early research is focusing on a capsule that can deliver a week’s worth of HIV drugs in a single dose. If confirmed in advanced research, such an option could allow patients to stay compliant with the dosing regimen required to fight the virus successfully.

  • The drug delivery capsule has a star-shaped structure consisting of six arms that can be loaded with drugs. The arms fold inward so that the structure can be encased in a smooth coating. After the capsule is swallowed, the arms unfold and release the drugs.
  • While antiretroviral therapy has improved treatment and prolonged the life expectancy of patients infected with HIV, several challenges limit its optimal performance. Such drug therapy often requires life-long use and complex dosing regimens, resulting in low patient adherence and periods of lapsed treatment.

Early research by scientists at MIT and Brigham and Women’s Hospital is focusing on a capsule capable of delivering a week’s worth of HIV drugs in one dose.1 If confirmed in advanced research, such an option could allow patients to stay compliant with the dosing regimen required to fight the virus successfully.

The team has developed a drug delivery capsule consisting of a star-shaped structure including six arms that can be loaded with drugs, folded inward, and encased in a smooth coating. The arms unfold and release the drugs after the capsule is swallowed. In data published in 2016, researchers reported that such capsules containing the malaria drug ivermectin could stay in the stomach for up to two weeks, gradually releasing the target medication.2 The scientific team then worked to adapt the capsule for delivery of HIV drugs.

“One of the main barriers to treating and preventing HIV is adherence,” says Giovanni Traverso, MB, BChir, PhD, a research affiliate at MIT’s Koch Institute for Integrative Cancer Research and a gastroenterologist and biomedical engineer at Brigham and Women’s Hospital. “The ability to make doses less frequent stands to improve adherence and make a significant impact at the patient level.”

Although antiretroviral (ARV) therapy has affected the medical landscape with improved treatment and prolonged life expectancy of patients infected with HIV, several challenges limit the optimal performance of such drugs.3 First, ARVs often require life-long use and complex dosing regimens, resulting in low patient adherence and periods of lapsed treatment. These behaviors can lead to drug resistance.

“We are all very excited about how this new drug-delivery system can potentially help patients with HIV/AIDS, as well as many other diseases,” states Robert Langer, ScD, the David H. Koch Institute Professor at MIT and a member of MIT’s Koch Institute for Integrative Cancer Research.

Focus on New Delivery System

In the current study, the scientific team at MIT and Brigham and Women’s Hospital designed a capsule that, once inside the stomach, opens into a star-shaped structure that is too large to pass through the pylorus. In this location, centered between the stomach and the small intestine, the star-shaped system could allow food to continue to pass through the digestive system while the study drugs diffuse slowly over time.

Since the capsule can hold multiple drugs at one time, the team looked at delivering the HIV antiretrovirals dolutegravir, rilpivirine, and cabotegravir. Such drugs are used for HIV prevention among non-infected patients and for viral suppression among HIV patients. To examine the efficacy of such delivery, scientists 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. They also used mathematical modeling in conjunction with the Institute for Disease Modeling in Bellevue, WA, to predict what happens when a patient misses a dose, and developed steps to improve prevention strategy.

Using simulations of viral dynamics and patient adherence patterns, the research suggests the new capsule system not only may lower the incidence therapeutic failures, but also may prevent thousands of new HIV cases.1 By converting from a daily to weekly dose, the calculations indicate that the efficacy of pre-exposure HIV prevention strategies could increase by up to 20%. When using models of populations in South Africa, where HIV incidence is high, the data suggest that using the new dosage form has the potential to prevent 200,000 to 800,000 new HIV infections over the next 20-year period.1

What Is the Next Step?

The scientific team now is working to scale up and validate results from preclinical models to move forward in delivering the potential therapy in advanced trials. One focus is to adapt the capsule to other diseases for which weekly drug dosing would be helpful. The polymer arms of the capsule will allow researchers to swap different drugs for ease of delivery. Scientists also are working to develop capsules that could remain in the body for longer periods of time.

“A longer-acting, less invasive oral formulation could be one important part of our future arsenal to stop the HIV/AIDS pandemic,” says Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, which partly funded the research.

Although progress has been made with antiretroviral therapies, a key challenge remains the lack of compliance with once-daily medications for infected individuals and pre-exposure prophylaxis (PrEP) for uninfected people who are at risk, notes Fauci.

“New and improved tools for HIV treatment and prevention, along with wider implementation of novel and existing approaches, are needed to end the HIV pandemic as we know it,” Fauci said in a press statement. “Studies such as this help us move closer to achieving this goal.”

REFERENCES

  1. Kirtane AR, Abouzid O, Minahan D, et al. Development of an oral once-weekly drug delivery system for HIV antiretroviral therapy. Nat Commun 2018;9:2.
  2. Bellinger AM, Jafari M, Grant TM, et al. Oral, ultra-long-lasting drug delivery: Application toward malaria elimination goals. Sci Transl Med 2016;8:365ra157.
  3. Kirtane AR, Langer R, Traverso G. Past, present, and future drug delivery systems for antiretrovirals. J Pharm Sci 2016;105:3471-3482.