Factors Considered in Choosing Initial HIV Therapeutic Regimen

Segment Description: Experts in infectious diseases provide an overview of the current HIV treatment landscape and factors considered in choosing an initial therapeutic regimen.

Joseph Eron, MD: Ian, where are we with treatment options? What are the first-line options for the newly diagnosed, their efficacy, and why do we choose these regimens?

Ian Frank, MD: HIV therapy is 1 of the amazing success stories of medicine since 1987. We have over 30 drugs now, but we are using a relative few number. If we discuss treatment guidelines, there are too many to consider. The Department of Health and Human Services [DHHS] and the IAS-USA Guidelines [International Antiviral Society—USA] both agree that therapy should start with an integrase inhibitor, such as the nonboosted integrase inhibitors dolutegravir, bictegravir, and raltegravir. The guidelines differ with respect to the nucleoside choices. The IAS-USA Guidelines say that if you’re using a 3-drug combination, you should use TAF-FTC [tenofovir alafenamide–emtricitabine] together with either bictegravir in the fixed-dose formulation of Biktarvy or together with dolutegravir.

Raltegravir is a preferred agent in the DHHS [Clinical] Guidelines but not in IAS-USA, because it has a lower barrier to resistance; it involves taking a few more pills. There is a new addition to the DHHS guidelines, and that is a fixed dose of dolutegravir lamivudine. It is the first 2-drug combination, 1-pill, fixed-dose combination to be a preferred agent. And we’ve got comparative studies that show that dolutegravir-lamivudine is as potent as dolutegravir-tenofovir FTC [emtricitabine]. This 2-drug combination is as potent as a 3-drug combination.

Almost everybody who takes these drugs consistently gets their viral load to an undetectable level. Resistance in people who don’t maintain virological suppression to the integrase inhibitors is uncommon if they’re on the second generation of integrase inhibitors.

Joseph Eron, MD: Very uncommon.

Ian Frank, MD: They’re safe. We have safe, potent combinations that will work effectively as long as people take them.

Joseph Eron, MD: In the past we used to think, “How high is their viral load?” or “How low is their CD4? Should we do something differently?” And this comes into play with our 2-drug therapy, the dolutegravir-lamivudine that you mentioned earlier, which is Dovato. Allison, are there some reasons you might not use that combination?

Allison Agwu, MD, ScM: I take care of a lot of adolescents. Oftentimes they’re not included in many of the studies. I tend to be a little nervous about using the 2-drug regiment. They typically don’t have a lot of other comorbidities that we need to think about when using a regimen. I think it’s great that we have them. Particularly as we think about long-term sequelae of being on just your HIV or being on antiretroviral therapy if you have the opportunity to use fewer drugs, there are fewer bone and kidney issues; it’s a good thing. Also, comorbid conditions are a part of what you think about. We don’t have to think about resistance as much. We used to be thinking about how much resistance we have when initiating therapy. We don’t really have that much. I can’t think of the last time I had somebody coming into care who had pretreatment resistance. It’s very rare. I oftentimes think about how pill size used to matter. But pills are smaller and smaller and more palatable. The adverse effects are minimal. Perhaps headache and nausea around the beginning, but that tends to go away.

I think about childbearing and what goes into it. If we’re thinking about dolutegravir, for example, there are some concerns about neural tube defects and women of childbearing age and when to use that would be important. And then adherence, again—even when people are not fully adherent, we’re not seeing a lot of resistance, but we do think about that in terms of the barriers. It would be the difference between using a raltegravir-based regimen versus using a dolutegravir- or bictegravir-based regimen.