Drug Resistance or Intolerance to HIV Therapy

Expert physicians in infectious diseases review drug resistance to HIV therapy and the challenges faced by these patients because of limited treatment regimen.

Joseph Eron, MD: Let’s discuss drug resistance. Ian, are we seeing it?

Ian Frank, MD: Drug resistance is a lot less common than it used to be. In Philadelphia, [Pennsylvania], with our needle exchange program, 90% of people who are injecting heroin every day have undetectable viral loads. I don’t think that is much different from most everybody’s practice. We’ve seen virological suppression rates of 90% in most clinic cohorts.

We don’t see resistance because the drugs work very well and have a higher genetic barrier to resistance. I still do resistance testing in people who are coming into care.

Joseph Eron, MD: There’s debate.

Ian Frank, MD: There is a debate. And most likely you’re going to see a resistance to the NRTI class [nucleoside reverse transcriptase inhibitors]. Even though I don’t typically start a patient on an NRTI-based regimen, I still want to know if it’s there. In a small percentage, maybe even to see a baseline and M184V, it’s helpful to know this. Because if people fail again, I’d like to know where they were previously.

Ian Frank, MD: Occasionally I’ll order a resistance test. I do have a handful of people who struggle taking their medications and develop resistance. But people on a boosted protease inhibitor [PI] don’t generally have PI resistance. People on a next-generation integrase inhibitor generally do not get integrase-associated mutations. We’re not seeing failure as much because these drugs do have a higher barrier to resistance.

Joseph Eron, MD: Do you have patients that have multidrug resistance? How do you treat them?

Ian Frank, MD: I definitely do. I have people who started out single nucleoside therapy in the past. A number of years ago, when dolutegravir and raltegravir were first available, I was able to get people on a regimen that for the first time was able to suppress virus replication. But they have protease resistance, and they have NUC [nucleoside analog] resistance, they have NNRTI [non-NRTI] resistance. I have people who started on raltegravir who have integrase resistance. I have some people for whom I am wondering when I will use the next-generation drugs that are available to us, and how to time that in a way that’s most likely to be successful with a long-term strategy in mind.

Joseph Eron, MD: Allison, can you talk about perinatal?

Allison Agwu, MD, ScM: Yes. We have patients who were the first kids ever to see any of these drugs, single agent, and then tell the story of the treatment of HIV. They harbor tons of resistance. For the first time 5 years ago, they were able to be suppressed. The challenge is that they can potentially become nonadherent; I need to know what’s in my armamentarium.

Joseph Eron, MD: Sure.

Allison Agwu, MD, ScM: I will say that with the elvitegravir-based regimens, we saw an accumulation of integrase mutation that can impact cabotegravir. This is 1 place I definitely think it’s useful if you see failure on earlier regimens.

The other place where I see quite a bit of resistance testing is in patients who immigrate from Africa and the Caribbean, where there are different regimens, and nobody is checking for resistance. Understanding what’s coming in, there’s a lot of transient resistance as well as a lot of failure, but no viral load testing in a lot of places.

Joseph Eron, MD: We’re fortunate that we don’t have very many people who are viremic and have lots of resistance. A lot of really complicated people have been suppressed. I have a few patients—if they ever rebound, I don’t know what I’m going to do. Occasionally we have someone who has very limited treatment options. There’s a newer drug, ibalizumab. Colleen, can you say something about it, ibalizumab?

Colleen Kelley, MD, MPH: Yes, ibalizumab is a monoclonal antibody that binds the CD4 receptor and prevents the virus from being able to bind the coreceptor. When the antibody is bound to the CD4, it can’t bind the TCR5 coreceptor. It is an infusion, and it is approved for heavily treatment experience, people with resistance, and no other options. Ibalizumab appears to be effective in treating those folks. I will say in our very large clinic, 6000 active patients, we really have only a handful, less than 5 that are even candidates for ibalizumab. We don’t have a lot of experience with the medication, but we are using it in very select cases.

Joseph Eron, MD: We have 2 people on ibalizumab. The goal is to give them other active components. It’s not going to work very well as a single drug, but occasionally we do have to do that.

Colleen Kelley, MD, MPH: Yes, often in combination with multiple medications.

Joseph Eron, MD: Now I think we can talk about what’s coming.