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Dolutegravir + Rilpivirine Combination Therapy for HIV

MAY 22, 2019 | PANELISTS: JOSEPH ERON, MD; PAUL SAX, MD; W. DAVID HARDY, MD; ERIC S. DAAR, MD; IAN FRANK, MD
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Segment Description: Joseph Eron, MD; Paul Sax, MD; W. David Hardy, MD; Eric S. Daar, MD; Ian Frank, MD, discuss the efficacy of the INSTI and NNRTI 2-drug regimen dolutegravir-rilpivirine and results of the SWORD-1 and SWORD-2 studies.

Joseph Eron, MD: Let’s talk quickly about 2 drugs, especially dolutegravir-lamivudine. Maybe Paul. Should we use it?

Paul Sax, MD: I think the data are very promising, especially from the GEMINI studies. We anticipated there might be some extra resistance from the ACTG [A5353] pilot study, a single-arm study. But so far, at least at 48 weeks of data, there was no resistance, and it was as good as dolutegravir plus TDF/FDC [a fixed-dose combination of tenofovir disoproxil fumarate], so that is very encouraging. And we are going to see a large study of switching patients who are stably suppressed from TAF [tenofovir alafenamide] regimens and comparing continuing TAF [tenofovir alafenamide] regimens with dolutegravir-lamivudine. So there definitely are some attractive aspects of it. One in particular is pharmacoeconomic. Lamivudine has been available since 1995. It’s been generic a long time. We totally know its safety track record, and our modeling studies suggest that this is really the most cost-effective way to treat people, especially if we can switch stably suppressed patients to dolutegravir-lamivudine. It’s not a good drug for that immediate start, that immediate regimen.

I think we don’t know about its resistance barrier. Transmitted 184V does happen, although it’s not that common. I would not be choosing it for that particular approach. We’ll say 1 other group for whom I’m still not totally comfortable using TAF [tenofovir alafenamide] is people with really moderate to severe renal disease, and these typically are older patients—older patients who have maybe been on tenofovir for years and years in its DF [disoproxil fumarate] formulation. And their creatinine clearance is 30 mL/min. or so, and you want to save those last nephrons. Why not switch them to dolutegravir-lamivudine or even dolutegravir-emtricitabine if you’re concerned about using lamivudine with impaired renal function. So those are 2 settings in which I feel very comfortable using it.

Joseph Eron, MD: Or dolutegravir plus rilpivirine. Maybe you could mention that.

Paul Sax, MD: It works.                                                                  

Ian Frank, MD: So there were 2 studies called SWORD-1 and SWORD-2, and really Paul introduced the concept of switching antiretroviral therapy. And I’ll just start by saying this is the most common decision that I’m making in my practice today. We have people who are on older regimens associated with high risk for toxicities or complicated regimens. We can simplify therapies. We can maybe eliminate the use of some drugs entirely or the need to take pills multiple times a day. So the SWORD-1 and SWORD-2 studies looked at people who were on classic 3-drug antiretroviral combinations and compared continuing that regimen with switching to dolutegravir and rilpivirine, which is now available in a single-tablet combination pill. And people did just as well. Virological suppression rates of 95% in people who switched versus continue. They couldn’t have had any baseline resistance to either of their components, which would likely not be the case in most of the clinical scenarios we’re talking about.

But whom would you use this combination in? Well, it could be somebody with some renal insufficiency. I have people who are on historic regimens, complicated regimens with multiple baseline or multiple nuke associated mutations, and this has enabled me to simplify regimens considerably. I’ve had a couple of patients now who have gotten older, who now have moved to Medicare, and so they’ve lost their commercial insurance. And there’s that doughnut hole in which you need to pay for medications potentially out of your pocket. Antiretrovirals are expensive, my friends.

Paul Sax, MD: But so is dolutegravir-rilpivirine.

Ian Frank, MD: It isn’t cheaper, but I’ve had people who are on complicated boosted protease inhibitor regimens with integrase inhibitors, really 5 individual antiretrovirals, who have been able to switch to this and simplify their regimen and cost saving.

Eric S. Daar, MD: Yeah, just a couple of caveats to this discussion. 1) For the dolutegravir plus 3TC, it is important to remember, Paul already alluded to the resistance issue, which is that everybody enrolled in that study was screened for any resistance. And a lot of people screened out of the study because they had any transmitted resistance.

Joseph Eron, MD: Right, good point.

Eric S. Daar, MD: You have to have their hepatitis B at some point soon because it’s only 1 hepatitis B drug, and it enrolled only people with viral loads of up to 500,000. So we’re going to have to live with that limitation. And then the dolutegravir-rilpivirine, same thing, it’s maintenance therapy for people who…

Paul Sax, MD: Never failed.

Eric S. Daar, MD: Never failed in the past. We just need to be careful.

Joseph Eron, MD: That’s how it was studied. But interestingly, that’s not on the package insert.

Paul Sax, MD: I saw that.

Joseph Eron, MD: It’s fascinating. I agree with Ian, because I’ve used that combination to simplify some pretty complicated regimens of people with NRTI [nucleoside reverse transcriptase inhibitor] and PI [protease inhibitor] mutations.

W. David Hardy, MD: And there are some data from that small experience in Spain in which they did switch people who had highly complicated regimens…

Paul Sax, MD: Sure.

W. David Hardy, MD: To dolutegravir-rilpivirine. It actually came out pretty well. So invoking 2 new classes to which there is now previous resistance.

Paul Sax, MD: It makes sense.

W. David Hardy, MD: Makes sense.
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