Considerations for Prescribing Therapy for HIV

William Short, MD, MPH, AAHIVS: When I prescribe an integrase inhibitor, I know the drugs are very efficacious, assuming that the patients take it. We know obviously one of the biggest barriers is if patients are not willing to take their drugs, they’re not going to work for obvious reasons.

But when they do take the integrase inhibitors, I’m quite confident they’re very efficacious. They’re going to get their viral load down to undetectable, which is we want, so they can reap all the benefits of the drugs. They’re going to be able to tolerate the regimen. They’re not going to have many adverse effects, and I’m not going to worry that with other drugs they use, there’s going to be drug-drug interactions. There are some drug-drug interactions with some of the integrase inhibitors. It’s things like magnesium aluminum, so people taking Tums. And it is not a contraindication, it just needs to be separated out and spaced in the timing of your drug. So I feel confident when I prescribe an integrase inhibitor that patients are going to get the desired effect they need.

I think one of the biggest barriers to taking medication, or antiretrovirals, is other barriers you would think about as to why someone wouldn’t get tested, why someone wouldn’t want to be in care. There’s still a lot of stigma associated with living with HIV, not only in the community but in the health system as well. There’s mistrust of providers. We still see racism, homophobia, and patients are fearful of that and as a result stay out of care, which is unfortunate because then they lose the beneficial effects the antiretrovirals can provide to them. Not only in terms of their health and wellness, but also in terms of transmission. We know now that taking antiretrovirals and getting your viral loads to undetectable can actually prevent transmission to an uninfected partner. And we’ve been living in an era where we’re now promoting the U=U campaign—undetectable equals untransmissible. And all this is as a result of taking antiretrovirals. So that’s the state we’re in right now.

We talk about low genetic barrier to resistance. We’re really talking about how many mutations it will take to make the regimen ineffective. And a drug that has a low genetic barrier to resistance needs one mutation and then you’ve lost at least part of the regimen. And then you worry about what’s going to happen subsequently to the other components of that regimen.

So when I’m prescribing a regimen, I’m looking for something that has a high genetic barrier to resistance, and all that means is you need multiple mutations for it to become ineffective, and that’s where we’re going. When we typically think of a high genetic barrier to resistance drug, we automatically think of the protease inhibitors, and specifically boosted protease inhibitors.

When you think about integrase, the early integrase inhibitors were low genetic barrier to resistance. Whereas the newer integrase such as dolutegravir and bictegravir, and hopefully when we move into injectables, cabotegravir, will be those high genetic barrier to resistance drugs.

Pill burden is a huge thing for patients. Most patients coming into me, whether they’re treatment naïve or treatment experienced, and even to the point where they’re in a salvage regimen, or are multidrug resistant, which thank God we don’t see as much now, everybody wants a single pill. Not everyone is a candidate for a single pill, but looking at what I see right now, most patients are eligible for at least a once-a-day regimen, and then hopefully we can get them to a once-a-day pill, so a single tablet regimen. You can’t do it for everybody. But compared to 10 years ago, we are using mainly once-a-day regimens, which is great.