Ryan Haumschild, PharmD, MS, MBA: What are the implications of nonadherence to standard background therapy while taking a medication specifically targeting the multidrug resistant HIV [human immunodeficiency virus]?

Daniel Driffin, BS, MPH: Again, I think it goes back to everything we were talking about. Prior to walking down that path, it starts with the conversation with your patient, ensuring you are mindful of what’s going on outside of the clinic. Again, that’s driven by structural determinants of health, housing, and insurance access. Do they have any mental health or behavioral health concerns? Are there ongoing substance use connectivities? I think prior to walking down any path like that, we start with who the person sitting in front of us is, and ensure that the relationship will be maintained. I oftentimes hear that it’s missing. Even as we think about CMS [Centers for Medicare & Medicaid Services], and even I would put in this same conversation the Ryan White [HIV/AIDS] program, ensuring that those clients who are the most vulnerable are included in this conversation from start to finish.

Ryan Haumschild, PharmD, MS, MBA: Great programs, and a great opportunity to keep improving those most vulnerable patient populations. Dr Lopes, you chimed in earlier and did a great job of giving an overview of the importance of patients receiving the right treatment. A lot of times optimal adherence is going to lead to optimal outcomes. If you could, provide us with a bit of background, what are some of the ways that clinicians can promote optimal adherence to HIV medication regimens and monitoring?

Maria Lopes, MD, MS: The first is shared decision-making. I think Dr Sension as well as Mr Driffin highlighted some of the issues around access to care and social determinants. In the payer world, we love predictors of nonadherence. Some of these predictors may also have to do with patterns of adherence, especially to other medications and how many other medications are you on. Are there data we may have that may help in this aspect of what does good need to look like from an adherence perspective, or [what are] predictors that you’re not going to adhere? If you’re not going to adhere, isn’t it interesting if we can develop tools and solutions to be proactive before patients stop taking their medication, and if we can assist with wraparound support services? I can’t stress enough the ability to meet patients wherever they may be on that journey. The home is becoming very much a third locus of care. As I think about injectables, every 6 months, every 2 months, how can we think about coordinating care so that perhaps one of the options, especially for those who don’t have transportation, we can do a home visit, be able to draw [blood for] laboratory tests, be able to coordinate care with a training provider, perhaps to even do a telehealth visit? Creating simplicity around how we access the care so that if you miss a 6-month dose, and you now have lost considerably, and you may have to restart a loading dose all over again, which adds to the cost and potential resistance.

Back to trying to understand drivers of nonadherence. Nonadherence is multifactorial, so how can we solve this? Perhaps there’s a role for [the pharmaceutical industry] here in above-brand strategies that deal with the social determinants and travel and transportation, as well as basic things like forgetfulness, and perhaps how we can solve this. Maybe also through digital tools or apps or being able to assist patients, especially if they have a smartphone, and how we can do a better job in improving some of these challenges. It has to be personalized because, at the end of the day, we can be trying to solve something that doesn’t apply to that patient, or is not solving the reason they’re nonadherent. Then we haven’t added value, so it has to be personalized.

Ryan Haumschild, PharmD, MS, MBA: Speaking about personalized medicine, we have mutational detection and things like that, but I think of personalized medicine sometimes just in the personalized way we provide education, because we know education helps support adherence, helps patients understand their own journey, and helps them to be engaged. Dr Lopes, you talked about shared decision-making. I truly believe in that. Dr Sension, specifically what education needs should be provided to patients with multidrug resistant HIV who are on both an optimized background regimen and add-on therapy to promote adherence and optimal outcomes? What education can we provide them to self-monitor their disease progression outside of just the typical provider or clinic visits?

Michael Sension, MD: I think to understand once again, that we want to keep their virus completely under control, completely suppressed. The way we do that is to have levels of drugs in their bodies at all times. I have that discussion, so that if they miss a dose for whatever reason, and the levels go down, that the virus has a chance to reproduce itself once again. In doing so, it might result in a mutation, which could allow their medicine to once again not have activity. People with multidrug resistance have had that happen over and over again, and I try to stress that, hey, this is our final shot. We’re really going to put it together, so let’s learn from mistakes perhaps of the past, lessons from the past, and how can we come together to make this final shot, if you will, have the best chance of success. I try to bring them in on this discussion.

Early on we used to have discussions like taking HIV medicine was like walking a tightrope. You could make 50 perfect steps, and if you make 1 wrong step, you go down every time. Because our regimens were fragile, had low genetic barriers to resistance, and just 1 little dip in drug levels that allowed replicating virus to occur would select for a signature mutation, and there was no going back. Then we kind of got a second chance with high barrier-to-resistance regimens, where it was like walking a tightrope but with a net underneath. You could get back on if you made a mistake. I think that now with our perhaps longer-acting regimens such as lencapavir, which has come into play, that has great blood levels for months after a single injection, the key is the optimized background regimen because that’s where the potential impact could be with the regimen itself. The long-acting [medication] has been given, you’re not coming back for 6 months, but now the importance is adhering to that background regimen.

In fact, in the clinical trial that just led to the approval of lencapavir, the CAPELLA study, they had roughly 9 individuals who did develop failure and failure with resistance. Half of those failures with resistance can be explained by missed doses, as evidenced by blood levels of the background regimen. They could clearly explain that the resistance occurred not from lencapavir itself because that was an injection that had good levels for 6 months, but it was the missed doses within the background regimen. I think that’s a real lesson to bring forward now as we are moving into 2023 and the lencapavir era, if you will, as we look to manage multidrug resistance.

Ryan Haumschild, PharmD, MS, MBA: You said a lot of important things there. But I would say one of them is keeping the patients motivated on therapy, understanding the implications, but also setting them up for success by providing them a therapy they can stay adherent to, to walk that tightrope but to be successful and come out the other side.

Transcript edited for clarity.