Nuances of First-line Antiretroviral Therapy in HIV

Peter L. Salgo, MD: What factors do you consider when you start considering a therapeutic regimen and who to put on what?

Ian Frank, MD: There’s one important virologic factor, which is resistance. Some people get infected with resistant virus. Based upon the drugs we use, that doesn’t necessarily influence a choice of therapy as much today as it had in the past, but it occasionally may. A lot of the factors have to do with the patient. Are they on other medications which could be associated with drug—drug interactions that could influence our choice? Do they have another disease that could influence our choice? Do they have heart disease? Do they have kidney disease? Do they have hepatitis B infection? Do they have hepatitis C infection? Occasionally, the viral load may influence our choice because there are a couple of drugs we may not want to use if the viral load is greater than 100,000—although it’s not my practice to use those drugs. I tend to prefer to use drugs that are as potent and effective irrespective of the viral load or a CD4 count. Those have been some factors that influence decisions.

Peter L. Salgo, MD: Personal approach and initial ART (antiretroviral therapy): what’s your standard? Like, all-comers, what would you choose?

Eric S. Daar, MD: It’s interesting. Since the beginning of potent, antiretroviral therapy about 20 years ago (in the mid-90s), it was 2 nucleoside analogs and a third drug. And here we are, 20 years later, and it’s still (for the most part) 2 nucleoside analogs and a third drug.

Peter L. Salgo, MD: What’s the third drug?

Eric S. Daar, MD: The third drug had traditionally been a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor. And then, more recently with the rollout of more and more integrase inhibitors, integrase inhibitors have really taken over as the predominant third drug for most people’s first-line regimens.

Peter L. Salgo, MD: How do you select the patients if you’re going to do all of these various complicated things? Run through some of these drugs and how you would parse them out.

Eric S. Daar, MD: If you look at the current guidelines, at least in the US guidelines, one of the guidelines only recommends integrase-based regimens. The integrase inhibitors vary a little bit. Some are once-a-day regimens, and some are twice-a-day regimens. Then, the biggest difference is often what they’re co-formulated with. Because, in addition to the discussion about how easy therapy is, how forgiving it is, and how there’s little reason to jump through all the hoops we used to, there’s also more and more single-tablet regimens where we’re not just treating people with easy regimens. We’re literally giving them 1 pill a day. But they’re not all co-formulated with all of the options.

Peter L. Salgo, MD: I think what scares a lot of the primary care doctors is a list like this.

Joseph Eron, MD: The list is shrinking. It used to be 2 pages long.

Peter L. Salgo, MD: Dolutegravir, abacavir, and lamivudine. I’m reading these off and I can barely pronounce them. Dolutegravir, tenofovir, alafenamide, and emtricitabine. Look at this menu.

Paul E. Sax, MD: Sure. To be a little more critical, some of these are better than others.

Peter L. Salgo, MD: So, tell me what’s better, and why?

Paul E. Sax, MD: I think the best integrase inhibitor is dolutegravir, and I don’t think that there’s a lot of doubt about that. It’s a once-a-day regimen, it’s very potent, and it has a remarkable resistance barrier, meaning people who fail treatment don’t get resistance to it. And you could combine it with any of the nucleosides, including with tenofovir, alafenamide, and emtricitabine, which is my personal favorite combination.

Joseph Eron, MD: think Paul’s point is that there really are maybe 2 or 3 initial regimens that you would pick from. Dolutegravir and Descovy, the problem with that regimen is it’s 2 pills and some people don’t want to take 2 pills. And then there’s dolutegravir/abacavir/lamivudine. That is 1 pill, but not everybody is as happy with abacavir as they are with TAF (tenofovir/alafenamide). Finally, there’s the combination that includes elvitegravir, which is the third integrase inhibitor. And the issue with that is it’s boosted. You have to give an inhibitor of P450, and that’s not the best thing to give people, necessarily.

Now, Paul’s going to fix this because Paul is working on a medication, which we’ll get to at the end, that actually has a lot of the advantages of dolutegravir, but is co-formulated with this tenofovir/alafenamide/emtricitabine. So, we’ll get to that at the end, but things are even getting better.

Peter L. Salgo, MD: But you do understand that for somebody looking at a list like this, it turns into word salad.

Paul E. Sax, MD: Absolutely.

Joseph Eron, MD: Yes, but the list used to be a page-and-a-half long. Now, if you read the guidelines, it’s down to 4 choices and they’re very, very similar. You could throw a dart at them and pretty much get it right.

Paul E. Sax, MD: I understand what you’re saying. If someone were to show me, for example, the drugs for rheumatoid arthritis, how could we choose that without using them every day? That’s really what you’re talking about.

Peter L. Salgo, MD: Familiarity breeds expertise.

Eric S. Daar, MD: And there’s certainly subtleties. So, when Paul said, “This is definitely what I would use, this is my preferred option,” there may be certain situations in certain patients where he might not.

Transcript edited for clarity.