Nuances of HIV Treatment

Peter L. Salgo, MD: How do you choose which regimen you’re going to use? Is it simply a side effect profile? Is it virologic effectiveness, or what? Where do you start?

Elly Fatehi, PharmD, BCPS: I’ll let you answer that.

Michael Sension, MD: Well, first of all, I think it’s fair to say that if people took 100% of their medicine, all the regimens would work.

Jeffrey Dunn, PharmD: No matter what it was?

Michael Sension, MD: It doesn’t matter what it is if they take 100% of their medicine. So, we have to think about all of those factors. What are the potential side effects? Have a discussion with patients. Some patients may say, “Well, I can handle that, but with this particular side effect, if I even get a little bit of it, that would not be good for me.” We have a discussion. Mental illness is a big thing that plays a part in our patient population.

Peter L. Salgo, MD: Oh, really?

Michael Sension, MD: Comorbid mental illness along with HIV can play a factor with potential adherence.

Peter L. Salgo, MD: You could roll into that the known association with HIV-associated dementia, too, which would make compliance more difficult.

Michael Sension, MD: Absolutely. That might lead you down the path of starting off with a regimen that we refer to as having a higher genetic barrier to resistance, having more difficulty to develop resistance, should there be missed doses.

Jeffrey Dunn, PharmD: I’ll just say that the question you asked is the same question that payers have.

Peter L. Salgo, MD: What’s that?

Jeffrey Dunn, PharmD: When we go to providers, as we’re trying to figure out how we can manage this, how do you decide which drug or which regimens—which STR—is the best for each patient? Because what we’re trying to do is put together a formulary that is best for the population, knowing that there’s always going to be a pathway for specific patients. Formularies are population tools. Generally speaking, payers just try to manage. We don’t want to practice medicine. We’re just trying to maybe manage that first choice. Can we come to some kind of consensus on what the appropriate first-line drugs and beyond are? We’re not going to get down to that level because that is a provider decision, and that’s not something that we’re educated enough to really play in.

Peter L. Salgo, MD: We have this term of art, this most-patients term, which is what the guidelines address. And then, they say there’s a carve-out for patients who don’t fit the most-patient category. You already alluded to psychiatric illness. We brought up dementia. What are the other carve-outs?

Elly Fatehi, PharmD, BCPS: For example, pregnancy.

Peter L. Salgo, MD: How so?

Elly Fatehi, PharmD, BCPS: You would need to avoid elvitegravir or cobicistat, which is actually an integrase inhibitor that would be considered in the recommended setting. That would be a drug that has to be avoided, so those are some things to think about. For chronic kidney disease, there are new products that are actually safer for kidney disease, the TAF (tenofovir alafenamide) products. So, you would focus on which medication you would use.

Peter L. Salgo, MD: What about those patients who come in—and I’m not going to say exceptionally sick, because I’m not sure if this correlates directly to symptoms 1-on-1—who are clearly worrisome, with very high CD4 counts or very low T4 cell counts? Is that part of the carve-out?

Michael Sension, MD: I think we have to consider that. Integrase inhibitors have been a wonderful addition to the classes of drugs that we have to use. But more recently, there have been data presented at the retroviral conference this past year from some large cohort studies, which showed that people with very advanced disease who get started on an integrase inhibitor-based regimen have higher rates of immune reconstitution syndrome. This was so concerning to the authors that they suggested that perhaps people with more advanced disease should start on a non—integrase-based regimen, perhaps a protease inhibitor-based regimen, because of this.

Peter L. Salgo, MD: Bring us into this. What is immune reconstitution syndrome?

Michael Sension, MD: When somebody’s immune system is severely suppressed or depressed from advanced HIV disease, they respond very dramatically to a reduction in their virus, and their immune system gets strong very rapidly, there can actually be a very prominent immune reaction that’s a direct result of the immune system getting strong very rapidly. It can cause an inflammatory response in many different organs, not necessarily a disease but an inflammation, related to a strengthening of the immune system due to immune reconstitution from effective therapy.

Peter L. Salgo, MD: That’s something we never even considered so many decades ago. What does this look like? Does it look like SIRS (systemic inflammatory response syndrome) or sepsis? What does the actual syndrome look like?

Michael Sension, MD: People can have fever; they can have inflammation evidenced by some liver enzyme elevation. It can be very prominent. It’s something that has been clearly identified in initial therapy. Because integrase inhibitor therapy reduces viral load at a much more rapid degree than other NNRTI (non-nucleoside reverse transcriptase inhibitor) and protease inhibitor-based regimens, the thought is that perhaps integrase inhibitor-based regimens might lead to a faster and more robust immune strengthening, which puts people at risk for this.

Peter L. Salgo, MD: That’s fascinating.

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