The Difficulty of Switching ART Regimens in HIV

Segment Description: A discussion on the use of tenofovir alafenamide (TAF) during hemodialysis, and the rationale behind switching antiretroviral (ART) regimens in viral suppression.

Paul Sax, MD: I just have a question for our moderator here. You don’t get to ask all the questions. You were involved in a study looking at the TAF [tenofovir alafenamide]—based regimen in hemodialysis. Instinctually, it doesn’t seem right to me to use TAF [tenofovir alafenamide] and emtricitabine in people on hemodialysis. What do you think?

Joseph Eron, MD: Well, I think that you can come up with other alternatives, though it depends. There are people who have very strong ties to tenofovir. In our clinic, we had people on 1 weekly tenofovir [disoproxil fumarate]—TDF, sorry—and the levels with TAF [tenofovir alafenamide] daily for people on chronic dialysis, and these were all people who were on chronic dialysis. They weren’t transplant candidates, so it’s kind of a different setting. But I think there are other alternatives. But if you need to, you can use it in that setting.

Paul Sax, MD: Right now I’m struggling with a very difficult case—I can get some consults here. A person has chronic hepatitis B and almost certainly has resistance to lamivudine.

Joseph Eron, MD: Right.

Paul Sax, MD: No, but now he’s suppressed.

Joseph Eron, MD: Oh, he’s suppressed.

Paul Sax, MD: Because he’s on TAF [tenofovir alafenamide]—based regimen. But he’s losing his kidney function because of aging and comorbidities, not because of TAF [tenofovir alafenamide]. I don’t think there’s a ready solution to that one.

Joseph Eron, MD: Sure. Yeah. No, I think that’s right. But in terms of tenofovir exposures, it will be quite low.

Paul Sax, MD: It’s good but higher than an estimated GFR [glomerular filtration rate of] 15 mL/min/m³ now.

Joseph Eron, MD: Yeah. But again, depending on his resistance profile, I think actually dolutegravir-rilpivirine.

Paul Sax, MD: But hepatitis B.

Eric S. Daar, MD: Except for the hep B.

Joseph Eron, MD: Oh, yeah, hep B—very important.

Eric S. Daar, MD: And entecavir.

Joseph Eron, MD: Entecavir.

Paul Sax, MD: This is someone who’s been infected since the early 1990s.

Joseph Eron, MD: I would use TAF [tenofovir alafenamide].

Paul Sax, MD: That’s what I’m doing.

Joseph Eron, MD: Let’s flip over to—anything else to say about switching? This is 1 of our topics.

Paul Sax, MD: If you ever want to have a setting where you’d want to get the HIV experts involved, it’s really before switching to ART [antiretroviral treatments]. I think a lot of our patients are so stable now that they could be managed by primary care, general internists, family practitioners, people who are not HIV specialists. But if you’re switching a regimen, get some input from somebody.

W. David Hardy, MD: I think the really important caveat about that is that we get opportunities to switch because new drugs keep coming out. I think there is some pressure on treating physicians to do something new and different instead of the same old thing that has always happened. There has to be a good reason to switch. There has to be a good reason to switch—not just because of the fact that this person told you that there’s a brand-new drug out there. So I think that’s actually the important thing, and when you do make that decision and you have questions, particularly about previous treatment history, you really need to get help with that. Because you can make bad decisions and actually cause harm by switching in not an appropriate way.

Joseph Eron, MD: Sure.

Ian Frank, MD: Although I would just say that there are studies that show people who are on efavirenz-based regimen who don’t report any symptoms associated with efavirenz feel better after a switch to a nonefavirenz regimen. I think it’s always worth talking to a patient who’s on an older combination to carefully discuss the presence of maybe some subtle symptoms that may be associated with that combination and careful attention to lipid levels and risk for, particularly on an efavirenz-inclusive fixed-dose combination. They’re on an older formulation of tenofovir with renal and potentially bone effects. So there are things to pay attention to. And although things aren’t broke, it doesn’t mean that things aren’t slowly deteriorating and maybe a more modern, less toxic regimen is something to be considered.

Joseph Eron, MD: I tell the fellows that patients have the right to be on the simplest, safest therapy possible. That’s kind of our job.

Paul Sax, MD: Definitely.

Joseph Eron, MD: And that fits into their life in terms of cost and cost-effectiveness for them because sometimes people…

W. David Hardy, MD: Safety.

Joseph Eron, MD: At least in North Carolina, sometimes the simplest regimens are sometimes not the affordable regimen. But in general, I completely agree with Paul that the problems that I’ve seen are people who get switched when there aren’t quite enough data or someone…

Paul Sax, MD: Hasn’t taken the time to really. I mean, this is why ID [infectious disease] doctors are paid so well. Everyone laughed immediately.

Eric S. Daar, MD: I’m not laughing. I’m writing that down.

Paul Sax, MD: Because we take the time and energy to go through all those historical resistance tests. They go back now to the late 1990s, and really you scrutinize them before making these changes. Because the stakes are very high. The last thing we want to do is switch somebody and have them get resistance to a new drug class, especially integrase class.

Joseph Eron, MD: Yeah, I agree.