A recently published study shows positive early results for a once-weekly HIV antiretroviral in pill form that slowly releases the medications. This study has garnered lots of media attention for the groundbreaking technology. Many news outlets, from NPR to Gizmodo, reported on the study as a major breakthrough to deal with patient adherence -- getting patients to take their medications daily, as prescribed. But issues of adherence are only partly about the patient. Researchers, providers, and community advocates alike say that there may be several reasons why this new technology, while promising, might not be a magic bullet to address the myriad issues that exist when considering real-world challenges to accessing treatment.
Instead of the development of newer drugs, this study, which was published in Nature Communications, highlights a different strategy: delivering existing drugs in a way that releases them into the body at levels needed to suppress HIV, but reducing the amount of pills taken from one per day to one per week. The researchers developed a pill with the recommended daily dose of four existing drugs: dolutegravir (Tivicay, DTG), cabotegravir, rilpivirine (Edurant), and tenofovir alafenamide (Vemlidy). They developed a six-pointed structure that looks like a star, containing enough medication for one week. That medicine wheel is encased inside a capsule. When swallowed, the capsule melts away, leaving the six-points to release the medicine over seven days. It's been likened to swallowing a small pill box. The study was conducted in pigs, likely because they have a very similar digestive track to humans.
According to the authors, the study was conducted to help address the problem of adherence. "Lack of medication adherence to ART [antiretroviral therapy] has emerged as a key barrier to successful HIV treatment and prevention," write the authors. "The average adherence rate to long-term ART is ~70% in both high- and low-income countries[.]"
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The Science Is Promising, but Still Far From Becoming Reality
"Although this technology looks promising, I think we need to keep in mind that so far the only data on this delivery system have come from animal models, said Charles W. Flexner, M.D., professor of Medicine Pharmacology and Molecular Sciences, as well as International Health, with John's Hopkins University, and director of Long Acting/Extended Release Antiretroviral Research Resource Program (LEAP). "There is quite a bit of safety and tolerability data that will be required in humans before this product can become reality."
While the approach is novel and has the potential to become a real product, many more steps are needed to prove it can work in humans. "Food or medicines stay in the pig stomach much longer than in the human stomach," said Melanie Thompson, M.D., chair with HIV Medicine Association (HIVMA) and principal investigator at the AIDS Research Consortium of Atlanta. "It's unclear how faster transit time in humans would affect the pharmacodynamics of these drugs, since 'gastric residence' seems critical to their success."
While questions remain about the way this can be translated into a viable product for people living with HIV, compared with research and development on other conditions, movement in the field of antiretroviral therapy has been fast-paced. At the advent of antiretroviral therapy in the late 1990s, people with HIV had many pills to take, some with competing requirements (number of doses per day, different time of day, food or no food, etc.). Now, many options are available for people living with HIV that have reduced the pill burden to one-to-two pills a day. Other studies are also underway that are investigating newer drugs that can be administered with fewer and fewer doses, including some long-acting injectables.
"There are a number of other long-acting delivery technologies already in clinical development, including new injectables and implants, that may turn out to be more useful," noted Flexner.
And, while researchers in this study cite adherence as one of the primary concerns driving the development of this once-weekly pill, advocates and providers weigh the pros and cons of a once-weekly pill in the lives of patients.
When comparing the potential benefits and challenges of long-acting injectables in development versus the slow-release pill design in this study, Tim Horn, deputy executive director of HIV and HCV Programs with Treatment Action Group (TAG), could see how they both really differ in terms of access needs.
"Once and if long-acting [antiretrovirals], are approved, it's going to require once-monthly injections," he said. "Where are people going to go for those? Are they going to be able to go back to clinics once a month for those [injections]? People who live out in rural areas may not be able to get to clinics or to a pharmacy for those injections." For this reason, Horn stated that the once-weekly pills might have an advantage over injectables for some people with HIV: A person could keep a long-term drug supply that wouldn't require a monthly clinic visit.
But there are still some questions about the viability of reducing prescriptions to once a week. "A lot of what we know is that once daily has advantages for adherence over multiple times a day," said Horn. "Are people going to able to remember to take their pill once every Saturday? We don't know enough there."
But it's not just a question of people's ability to remember to take a pill once a week. Adherence challenges only partly have to do with a patient's desire or willingness to take his or her meds. Interruptions in health insurance coverage, transportation, mental health, housing, and other barriers can create challenges for people to maintain their connection to care and/or ART. There is also some research showing that 100% adherence is not necessary to prevent virus rebound or to maintain viral suppression.
"We should be cautious in thinking that adherence problems will be solved simply by pharmacology, said Thompson. "So, let's continue to work on new drugs and new formulations, but we must remember that they are ultimately only as good as the systems that deliver them and the ability of people to get in care and stay in care."