Single-Tablet Regimens for Treating HIV

William Short, MD, MPH, AAHIVS: Looking at the patients I take care of, I think what they’ve done is a couple of things. It’s given those who were taking maybe Prezcobix, or darunavir, ritonavir, 2 or 3 drug regimens, the ability to finally take 1 pill once a day. So for some reason they couldn’t be on some of the other classes. You know when someone was on a protease, we really didn’t have the ability to give someone a single-tablet regimen. So now we do.

I think the other, really, the benefit of having this is it’s another drug I have in my armamentarium. When I see someone who presents to me, do I want to use a protease inhibitor? Do I want to use an integrase inhibitor? And now I have a single tablet to do it.

I think of the things I didn’t talk about—and this really stems back, I think, in history to the evolution of antiretrovirals—is that when you give someone 3 drugs, a lot of times 2 of the 3 drugs, one is dependent on the other. So if you’re using a booster, let’s say you’re using darunavir with ritonavir, cobicistat [cobi], you really need that cobi or the darunavir to boost the levels of darunavir. But if you’re giving 3 drugs, there’s a chance that someone may miss, maybe they’re off in their pharmacy from picking up cycles, so you do need those 2. So you run the chance that you’re not going to get the levels you need and then you worry about virologic failure. Here, again, it’s 1 single pill you have.

I think again one of the other big advantages …and there’s really good data now from the DIAMOND trial, which was also looking at patients who were newly diagnosed with HIV—it was a single-arm trial—they were basically started on Symtuza or the darunavir-cobi single-tablet regimen. And basically with that they were shown, without having any lab data, no genotype, that they actually did pretty good on it. They really got down to virologic suppression. So this was in a population where you were doing a rapid start initiation right after diagnosis. So again, this gives me another drug or option that I can use for my patients. So when I’m thinking about patients for, again, the fixed dose of darunavir, cobi, emtricitabine, and tenofovir alafenamide, again I’m thinking about patients who first, I’m unsure about adherence. So they have unclear adherence to me. I’m not sure if they’re going to be able to adhere to a regimen. And I want to have a drug where I’m going to be sure that they’re not going to get resistant to it and blow future options. So that’s the first group.

Two, if I’m going to do a rapid initiation scenario. So if I have someone who I bring in, I know nothing about their history, I don’t have labs, I don’t have serum creatinine to look at their kidney function, I don’t have genotypes, I don’t have hepatitis serologies, I feel confident giving them a drug like Symtuza where they can start on it and then I can wait for my lab results to come back and genotype. And then I think for those patients who are suppressed and I don’t have records, I feel confident that making the switch to Symtuza would be a good choice and I’d be able to maintain virologic suppression.

The benefits I think when you look into the single tablet are, 1, you have the patient, you’re ensured that they are going to take all the components. Because, again, even though it’s a single tablet, in that single tablet you’re going to have a minimum of 3 or 4 drugs. And so you’re guaranteed they’re going to take it. I think the other thing is the pill size has gotten smaller over time, and we know that patients are going to be able to take it. So I think having everything in a single tablet, it’s really like, it’s a benefit all along. And we do have now a good number of single tablet regimens that are available for patients in multiple classes. And, again, with the latest approval of Symtuza, we actually have a protease inhibitor.

So I think one of the things I’ve seen over time when looking at clinical trial data is that really when you look at the safety and tolerability, what you see I think are a couple of things. The percentage of adverse events, and the way they’re graded is on a scale of 1 to 4, we use a system that we use in clinical trials where largely the best way to think about it is grade 1 is mild, grade 4 is severe. Most of the reactions we’re seeing, so first of all that there are very low percentages of adverse reactions. And in addition to that, most of them are grade 1, or mild. So that’s something that’s definitely changed. Where we had drugs where you saw 20% diarrhea, we’re not seeing that all. We’re seeing very low percentages. So that’s something that’s changed.

And the other piece that goes with it, because, again, patients are going to have side effects when you first start a new regimen. But I think the key is, what percent discontinue the drug due to those side effects, and those numbers are typically one 1% to 2%, so they’re really low. Again, this is very different than what we had historically looking at previous antiretroviral trials.