Transcript (slightly modified for clarity)
Peter L. Salgo, MD: Let’s take a look at some of the new maintenance strategies—induction strategies. Who wants to start us off by talking about the most recent switch maintenance trials?
Ian Frank, MD: I can talk about some of these studies. The strategy for switch is this: if your viral load is undetectable and you have no resistance, you can switch to almost any other, even modestly effective, combination and the switch will work. For example, there’s a combination Paul mentioned: rilpivirine, FTC (emtricitabine), and TAF (tenofovir alafenamide). And there have been a couple of new studies with that particular combination. Rilpivirine is not a drug that we would use in somebody whose baseline viral load was greater than 100,000 copies or whose CD4 counts were less than 200. Bu, if you look at people whose viral loads are undetectable on tenofovir/FTC/efavirenz or on the older formulation of tenofovir/FTC/rilpivirine, and you switch them to TAF/FTC/rilpivirine, they maintain virologic suppression just as effectively as if you continued them on their previous therapy. I think that that kind of study is just representative of all of the switch studies. If you’re virologically suppressed and there’s no history of resistance, you can switch, almost adlib, to any other effective combination therapy.
Joseph Eron, MD: I totally agree with what Ian says. Where you see risk in a switch is where someone is on kind of a high variant drug, like a boosted protease inhibitor; you don’t know their resistance history; and then you switch them to a lower barrier, like a NNRTI (non-nucleoside reverse transcriptase inhibitor), for example, or even some of the integrases, like elvitegravir or raltegravir. There’s some risk there, but there are no studies like that because the companies don’t want to do that kind of risky stuff in studies. What’s happening, I think, is there’s also a de-intensification. Can we go down to 2 drugs? And there are even studies going down to 1 drug, and I think those are kind of on the edge in some respects.
Paul E. Sax, MD: My thoughts on the 2-drug regimen, especially when 1 of the 2 drugs is a protease inhibitor and the other one is lamivudine, is that there are now enough randomized data that you could take someone from boosted protease inhibitor plus 2 nucleosides and switch them to boosted protease inhibitor plus lamivudine or emtricitabine, and they will maintain suppression just fine. That was done in the darunavir study that was just presented in Glasgow.
Peter L. Salgo, MD: Just so that we recognize what you said: there’s the switch from TDF- (tenofovir disoproxil fumarate) to TAF-containing antiretroviral therapies?
Joseph Eron, MD: Yes, no brainer.
Peter L. Salgo, MD: The DUAL-GESIDA 8014 study?
Paul E. Sax, MD: Yes, that works fine.
Ian Frank, MD: That’s what Paul was talking about.
Joseph Eron, MD: So basically, simplifying from boosted protease inhibitors and 2 nucleosides to boosted PI and our best tolerated nucleoside, which is 3TC (lamivudine) or FTC. And while the most recent one was with darunavir, there’s one with lopinavir and there’s ones with atazanavir—there’s a ton of data.
Paul E. Sax, MD: They all work.
Joseph Eron, MD: It works.
Peter L. Salgo, MD: And then there’s the DOMONO study. What is that?
Paul E. Sax, MD: I’m not so keen on that one.
Peter L. Salgo, MD: Tell me about it.
Paul E. Sax, MD: Well, it’s just using dolutegravir, which I’ve alluded to, which I think is our best integrase inhibitor as the sole treatment for people who are virologically suppressed. And it’s not as if that is necessarily giving them any benefit, except for only maybe saving money. I don’t see that.
Joseph Eron, MD: There’s just no compelling reason to do it.
Paul E. Sax, MD: Yes. I just don’t see the reason to do it. It’s also the fact that in some of the studies, there’s been a little bit of virologic rebound and some problems.
Ian Frank, MD: In that study, it gets reported as noninferior. But I think if you look at that data carefully…
Joseph Eron, MD: They have a crazy endpoint, which is a viral load of 200 for people who have been suppressed forever. That’s not the right endpoint.
Ian Frank, MD: Less than 50. And if you look at the less-than-50 data, people are not being maintained at the same rate of suppression if they’re on dolutegravir monotherapy.
Paul E. Sax, MD: We did this with protease inhibitors. We tried the monotherapy approach and it didn’t really work. I don’t think it’s going to work.
Eric S. Daar, MD: It just didn’t work quite as well.
Paul E. Sax, MD: Right.
Eric S. Daar, MD: The same thing is probably going to be true with this, so you’d have to have a really good reason to do it and it’s hard to think of one.
Peter L. Salgo, MD: But do you realize what you’re all saying? You’re talking about, “It’s really good” or “It’s really, really good.”
Ian Frank, MD: You can’t mess up with HIV because HIV will become resistant and it will limit your options.
Joseph Eron, MD: You don’t have infinite choices. You have lots of choices, and you can rescue most people. But if you start blowing your integrase inhibitor, you’re going down a slippery slope that you don’t need to go down.
Ian Frank, MD: So, why do that? These studies of these abbreviated regimens are basically coming out of Europe, and the reason is cost is a much greater consideration for the choice of regimens in Europe than in the United states. And in our country, fortunately, we still have a healthcare system that is willing to pay for these medications. I think it is a huge mistake to try to shave the number of drugs down to the smallest number that is going to be effective.
Eric S. Daar, MD: You have to have a better reason than just saving money if there’s a potential risk, and there are risks. A lot of people have done these avant-garde—type switches and they’ve blown up in their face. So, I think we have to be careful. When we originally did the boosted PI/lamivudine studies, it was because it was a compelling reason to try to avoid tenofovir and abacavir in a subset of people. We don’t have as compelling a reason now as we used to.
Peter L. Salgo, MD: And, again, correct me if I’m wrong: when you say they’re expensive (the therapies that we’re using), it’s really expensive to get a population of people with rebound and lots of virus and then everything explodes. It’s not just the cost of the drugs here that we’re talking about.
Eric S. Daar, MD: Yes.
Paul E. Sax, MD: HIV therapy does stand the test of cost-effectiveness because the health benefits are so huge—even at their relatively high cost.
Peter L. Salgo, MD: You’re talking about cost per year of life; that’s really where the answer is. For society, too. Even with the expensive therapy, if you prevent the spread of this virus, then you do keep the virus contained.
Paul E. Sax, MD: Definitely.
Peter L. Salgo, MD: And that’s different, and that’s important, isn’t it?
Paul E. Sax, MD: It’s been projected that if you have enough people virologically suppressed, the epidemic will eventually end. That could happen.