Safety Profile and Costs of Initial HIV Therapeutic Regimen

Segment Description: Colleen Kelley, MD, MPH, and Julia Marcus, PhD, MPH, discuss the metabolic issues as well as the costs associated with the initial therapeutic regimen.

Interview Transcript (modified slightly for readability):

Joseph Eron, MD: Some disease states direct us toward choosing a tenofovir-containing regimen, such as for a patient with hepatitis B or an advanced disease state with low CD4 where we might not use a 2-drug therapy. I think that’s another potential issue.

We have 2 or 3 choices for initial therapy. It’s not that complicated. This is indicative of how good things are. However, we are now worried about weight. Some therapies could contribute to weight gain. Colleen, have you seen that in your practice?

Colleen Kelley, MD, MPH: Yes, absolutely. Historically metabolic issues have been a concern with antiretroviral agents. But this specific rapid weight gain that we’ve seen with some of the integrase inhibitors was a little surprising. I have switched people off their regimen because of weight gain and the new onset of diabetes as well as other metabolic issues.

I think the jury is still out on exactly what the cause of that is, kind of mechanistically, and in who might be at risk specifically. But I do believe it is an issue for a minority of patients, but you will see it if you treat enough people with the integrase inhibitors. So it is something to keep in mind. It doesn’t necessarily change what I’m going to do to start, but my awareness is heightened. I’m looking out for it.

Joseph Eron, MD: Ian, do you tell people anything different in regard to therapy?

Ian Frank, MD: I do. I tell them that they may gain weight. And it’s potentially more of an issue for women than it is for men. It may not just be the integrase inhibitor, the component. There’s evidence that it might happen more in people who are on TAF [tenofovir alafenamide] than TDF [tenofovir disoproxil fumarate].

Everybody who starts antiretroviral therapy on average gains some weight. But here we’re talking about excess weight gain. In 1 study called ADVANCE, over a 96-week-period the average weight gain of women on TAF [tenofovir alafenamide], lamivudine, and dolutegravir was 10 kg. That’s a lot of weight.

I tell my patients that now that their body is not fighting HIV and burning more calories in the immunologic battle to control their infection, they’ve got to cut down the amount of food that they’re eating in order to be metabolically at equilibrium. I tell my patients to let me know if they’ve noticed that they’re starting to gain weight, because occasionally you do need to switch people off and use an alternative regimen. Maybe we should talk about what that regimen would be.

Joseph Eron, MD: In a moment let’s discuss SWITCH. But before we do, is there any reason to use a boosted drug as a first-line therapy? Meaning a fourth agent in the mix to prop up 1 of the other agents? Is there a reason to do that?

Allison Agwu, MD, ScM: I do not use a fourth agent as an initial therapy. All the boosted regimens are now an alternative or non-preferred, and there has to be some special circumstance for using them.

Ian Frank, MD: A boosted protease inhibitor may not be a bad combination for an adolescent or somebody who you’re worried about adherence if you’re not getting any baseline resistance testing. It’s true that with an integrase inhibitor regimen, a second-generation integrase inhibitor regimen, there’s probably low probability of baseline resistance. But the DHHS [Department of Health and Human Services Clinical] Guidelines do endorse a boosted protease inhibitor. I’m not talking about using it as a fourth drug. I’m talking about a 3-drug combination; a boosted protease inhibitor is a preferred regimen for immediate start.

Allison Agwu, MD, ScM: Think back to the darunavir regimen for adolescents, the pill burden, the size, and the resistance profile. I would favor going to bictegravir for adherence than using darunavir.

Ian Frank, MD: There’s now a 1-pill fixed-dose combination, so it’s not a pill burden.

Allison Agwu, MD, ScM: It’s a larger pill.

Joseph Eron, MD: In fact, it’s smaller. Somehow they got 4 drugs and combined them. It’s smaller than the 2 drugs. Julia, I know in the United States we don’t really talk that much about cost of drugs. You mentioned generics. How do we balance this? At some point this will need to be addressed.

Julia Marcus, PhD, MPH: There’s a federal initiative to end the HIV epidemic, and the key pillars of that initiative are treatment for everyone who needs it and PrEP [pre-exposure prophylaxis]. Antiretroviral medications are really the solution all around, but they’re incredibly expensive. And the estimates of the costs that it would take to end the epidemic are potentially beyond what society can withstand. So we have to think about it. I don’t know what the solution is, but it’s a problem.

Joseph Eron, MD: I’m starting to see it in my practice. We talked about the 2-drug combination of dolutegravir-lamivudine. I’ve now prescribed that a few times and was told, “Well, you can give them the dolutegravir, but you have to get generic lamivudine.” You can’t give them the single tablet. I’ve had a couple of instances where for the TDF-FTC [tenofovir disoproxil fumarate—emtricitabine], I was told, “No, you can give them TDF-3TC [tenofovir disoproxil fumarate–lamivudine], because that’s generic and less expensive. From the patient point of view, they see a different expense because generics don’t have a co-pay card, for example; whereas the trade drugs might have a co-pay card, so you switch them to generic, they actually have a co-pay.

Julia Marcus, PhD, MPH: Although maybe just to mention in the context of PrEP, the US PSTF [Preventive Services Task Force] recommendations are hopefully going to wave cost sharing for all PrEP medications starting next year.

Joseph Eron, MD: Oh, great.

Julia Marcus, PhD, MPH: Even though there may be more patient-assistance programs for the brand-name medications, it may be that there’s no cost sharing for any of them.

Joseph Eron, MD: That would be fantastic. Especially with PrEP, small barriers can be a really huge disincentive for people that have trouble persisting. And you may think, “Oh, well, it’s $10.” But it could be the difference between a 17-year-old taking it or not taking it, right?

Julia Marcus, PhD, MPH: Or a healthy person who is HIV negative who has no reason or motivation, to be honest—except for prevention—if it’s going to cost you something or if the complexity of figuring out how to get the cost covered is just too much.