Management of Patients With HIV, Limited Treatment Options

In this podcast, Charles Flexner, MD, speaks about a clinician's approach to managing a patient with HIV and limited treatment options, including choosing a new treatment regimen, understanding the underlying processes that caused previous treatment failures, and what is on the horizon for research in the management of patients with HIV and limited treatment options. Dr Flexner also participated in a symposium on these topics titled "Managing HIV Patients With Limited Treatment Options" at IDWeek 2022.

This podcast was recorded before IDWeek 2022. 

Additional Resource:

• Kuritzkes DR, Gandhi M, Flexner CW. Managing HIV patients with limited treatment options. Talk presented at: IDWeek 2022; October 19-23, 2022; Washington DC. Accessed October 19, 2022. 

Charles Flexner, MD, is a professor of international health at the Bloomberg School of Public Health and a professor of infectious diseases and clinical pharmacology at the Johns Hopkins University School of Medicine (Baltimore, MD).

TRANSCRIPTION:

Jessica Bard: Hello, everyone and welcome to another installment of Podcast 360, your go-to resource for medical news and clinical updates. I'm your moderator, Jessica Bard with Consultant 360, a multidisciplinary medical information network. Dr. Charles Flexner is here to speak with us today about a symposium in which he participated at IDWeek 2022, titled, "Managing HIV Patients with Limited Treatment Options." Dr. Flexner is a professor of international health at the Bloomberg School for Public Health and a professor of infectious diseases and clinical pharmacology at the Johns Hopkins University School of Medicine in Baltimore, Maryland. Thank you for joining us today, Dr. Flexner. Could you please provide us with an overview of this session?

Dr Charles Flexner: We're going to have a one hour symposium, which will include my colleagues, Dan Kuritzkes and Monica Gandhi talking about how to deal with patients with HIV infection, who either are having a difficult time having their viral load suppressed to below the limit of detection or people who have difficulty, because they're on a very complex medical regimen and there are questions about how to optimize adherence, reduce side effects, and prevent drug-drug interactions with such a complex regimen. These are pretty common problems for the HIV practitioner these days.

Jessica Bard: What should a clinician's approach to managing a patient with HIV with limited treatment options be and how does one go about choosing a new treatment regimen?

Dr Charles Flexner: Well, the first step is to discern which drugs the patient's virus has retained sensitivity to. Fortunately, because we have so many new agents, we can almost always come up with a two or three drug regimen to which the patient's virus is likely to respond. For example, the drug, fostemsavir that was recently approved for oral administration. Many patients who are heavily treatment-experienced and have multi-drug resistant virus will respond to that drug. In addition, patients who have never received an integrase inhibitor have that available to them as an option, or even if they failed therapy on a first generation integrase inhibitor like elvitegravir, or raltegravir. They may retain some level of sensitivity to dolutegravir or bictegravir. Those drugs provide options for heavily treatment-experienced patients that we did not have access to until very recently. Another recently approved drug that some patients may benefit from is ibalizumab, which is a drug that blocks the binding of HIV to one of its receptors.

That drug, however, has to be given intravenously every two weeks. That may be inconvenient for some patients. But if it's a drug you need, then it's a drug you may have access to and you may benefit from. Then finally, there are investigational drugs out there that do not share cross-resistance with other approved classes of antiretroviral drugs. For example, lenacapavir, the capsid assembly inhibitor being developed by Gilead does not share overlapping resistance with any other class of antiretroviral drug and represents a possible drug to be used in this patient population.

Jessica Bard: Now, in your expert opinion, what must providers be aware of when understanding the underlying processes that caused previous treatment failures?

Dr Charles Flexner: Well, it's been the case for a number of years and it is still the case that almost all patients, who have failed multiple classes of anti-HIV drugs have done so because of some degree of nonadherence. It's very important when you're beginning a new regimen with such a patient that you understand the situation that may have contributed to their nonadherence in the first place. That can include things like their social milieu, as well as underlying mental illness, or substance use. It's very important first and foremost to get a handle on those issues to the best of your ability before even attempting to treat such a patient with a new regimen. Once you begin therapy, it's important to counsel such a patient on the importance of strict adherence to their new regimen, so they don't wind up six months or a year from now in the same place they were at the outset of their treatment with their new regimen.

Jessica Bard: That's something that we hear of a lot when talking about nonadherence with clinicians. What would you say is next for research on the management of HIV patients with limited treatment options?

Dr Charles Flexner: The first and foremost issue of interest to most of us is the ability to use long-acting injectable formulations. For example, cabotegravir-rilpivirine or the drug I just mentioned, lenacapavir in this patient population. Many of us believe that, this may be the best way to circumvent nonadherence with daily oral therapy for many of our patients. A lot of us are looking forward to the possibility of understanding the benefits of long-acting parenteral therapy in this patient population. That includes considerations of drugs with very long dosing intervals like lenacapavir, which will be given in the maintenance phase as a subcutaneous injection every six months. But there are also long-acting, broadly, neutralizing, monoclonal antibodies that could be given as an intravenous infusion every three to six months. These treatments will only continue to improve and should provide a new way to manage these difficult to treat patients.

Jessica Bard: What would you say are the overall take home messages from our conversation today and also from your presentation, if a clinician is leaving your session, what do you want them to take home?

Dr Charles Flexner: Number one, there is an optimistic message about the potential benefit of new formulations and new drug classes for the management of heavily treatment-experienced patients and patients who are having a difficult time in whom we are having a difficult time suppressing their HIV viral load. In addition, we have a good understanding of the underlying cause of treatment failure in most cases, and that is nonadherence. There are a number of improving ways to manage the nonadherent patient, both in terms of assistance from family and from staff and clinics, smart devices and reminders on cell phones, for example and other ways to make sure that the patient is actually taking the medication they've been prescribed. Finally, there are a number of web-based and smartphone-based technologies that can help manage these complex patients. For example, smartphone apps to understand and manage potential drug-drug interactions involving antiretrovirals and other drugs in a complex medical regimen. We're going to become accustomed to using these technologies more and more to manage the difficult to treat patient.

Jessica Bard: Dr. Flexner, we so much appreciate you being on the podcast today. Is there anything else that you'd like to cover that you believe we missed?

Dr Charles Flexner: Although, people often feel a sense of despair when trying to understand the best way forward for such a patient, the number of options for treating and managing such a patient really are growing, and the future looks quite bright.

Jessica Bard: Well, thank you again.

Dr Charles Flexner: Thanks, Jessica. It was great to be here