Considering Two-Drug HIV Regimens

Joseph Eron, MD: There are some recent strategies that explore being able to simplify to 2 agents, instead of 3. Dan made the case for 3 agents, and it happened to be the right number. But, it’s possible, in people who are suppressed and maybe even in people who are starting therapy, which we’ll talk about later. So, what about simplifying to 2 agents? Is that ever something we should do?

Colleen Kelley, MD: Yes, it’s possible. Particularly, right now, in those people who are suppressed, we could consider switching them to a dolutegravir and rilpivirine-based regimen, which was recently approved. I have found this to be useful in that situation that I was talking about—the hospitalized patient who comes in with a new diagnosis. It’s renal failure, or it’s some other condition. They need an anticoagulant or something like that. I really feel like we need to drop the other medications that could be contributing to their illness.

Joseph Eron, MD: Yes, I would agree with you. This is especially true in some of our patients, as they get older. People have looked at comorbidities, and HIV, and counting them. Some of our patients have a lot of comorbidities. In the south, we know about diabetes, hypertension….

Colleen Kelley, MD: Heart disease, yes.

Joseph Eron, MD: Yes. Heart disease and renal disease. Sometimes, a 2-drug therapy may be what fits for them. The dolutegravir with rilpivirine—we do have to be careful with rilpivirine. It does have the drug interaction with proton pump inhibitors [PPIs], and it should be taken with food. But, it’s also a small pill.

Eric Daar, MD: Yes, I think you’re right. It’s still rilpivirine. We have to remind everybody of that—all of the usual caveats. But, for the person who is taking it with food, and is avoiding acid reducing agents, particularly PPIs, it’s a viable option. Dan talked about that conundrum that we have with these people who have a lot of comorbid conditions—diabetes, hypertension, renal failure—where abacavir may not be the best choice based on our concerns about abacavir and cardiovascular events. And tenofovir, although TAF [tenofovir alafenamide] has opened the door a little bit, for people down to a creatinine clearance of 30, or people who are experiencing progressive declines in renal function, I’m not sure that avoiding tenofovir wouldn’t be a good thing to do. Now, we have 2 giant fully powered studies looking at safely switching people to dolutegravir/rilpivirine.

Daniel Kuritzkes, MD: Joe mentioned the magic number. We hit on 3 drugs because we started out with 2 relatively weak drugs and added the third drug, which was very potent. Over the years, there have been attempts to look at some 2-drug regimens. Now, we finally have 2-drug regimens that are highly effective, at least for maintenance. We’re still exploring it for initial therapy. I think we have to start asking, “Well, if 2 drugs work, then why do you need that third drug?” And, “Is there some unproven advantage, long term, to being on less drug if you don’t really need that third agent, as well-tolerated as it may be, to sustain virologic suppression?”

Joseph Eron, MD: That is one issue with the studies that we’ve had in simplifying to 2 drugs. Maybe, because they’re shorter term, meaning 48 or 96 weeks, they really haven’t shown much in the way of the toxicity advantage? It’s possible, over a very long period of time, that may come up.

Eric Daar, MD: And until recently, most of that’s been boosted protease inhibitor/3TC-based regimens.

Joseph Eron, MD: Good point.

Eric Daar, MD: So, no single tablets and all of the baggage that comes with the boosters.

Transcript edited for clarity.