Virological Failure or Rebound to HIV Therapies

Segment Description: Allison Agwu, MD, ScM, reviews the causes of virological failure or rebound to HIV therapies and the relevance of rapid initiation of therapy.

Interview Transcript (modified slightly for readability):

Joseph Eron, MD: Allison, what about virological failure and rebound? I’m sure you see it in your practice. What’s the cause of it, and how do you treat these patients?

Allison Agwu, MD, ScM: We are seeing it much less than we used to, and it speaks to the potency of the regimens that are available. I get nervous when I see low-volume viremia because it’s so easy to become undetectable. If a patient keeps being at 150 copies/mL, I start to worry if they are really taking their pills, even though we know nobody’s a failure if they’re less than 200 copies/mL. But that being said, in our adolescent clinic, about 20% of our kids have biologic or virological rebound.

This is the patient I treat. Nationally 12% are suppressed for adolescents, so we have bigger problems. For adults, about 25% of those live with HIV and are suppressed. But I think when we see it, oftentimes there are system issues that have gone on. I have to address if the drug is covered or if the pharmacy sent out 1 medicine and not the other medicine. Some patients are taking part of a regimen if they have the funds to get it and the means of transportation to purchase it. So there are many things that go into whether you were able to take the medicine. Then the reality is, it’s hard to take your medicine every day.

It could be 1 pill once a day, but it’s 1 pill once a day that you have to take that comes along with the stigma that goes into it when you take it. And there are real implications for that. Which is why I’m so excited about—and we’ll talk about later—some of the long-lasting or long-acting regimens that will eliminate that issue. So there are system, individual, and more systems issues that tend to impact adherence. But usually it’s adherence that’s causing it.

Another point to make is that you should make sure there are no drug interactions and somebody’s not all of a sudden taking an antacid, a calcium-containing agent that’s actually absorbing their medicine, or some herbal medication that’s impacting their treatment.

Joseph Eron, MD: How do you walk through those personal, home, and system issues? How do you address that? If someone comes in, and they’re on an initial regimen that you know has been effective for so many people, yet their viral load is still a 1000 or 5000 copies/mL when it should be less than 20 or 40 copies/mL. How do you walk through that?

Allison Agwu, MD, ScM: I’ll say that it is not just me, but it’s everybody. It’s the nurses, the specialists—it’s really the team that’s making sure. Our pharmacist says, “Hey, it’s been 2 months since you got your medicine. What’s going on here?”

Joseph Eron, MD: Right, sure.

Allison Agwu, MD ScM: It’s a team approach to figure that out and let the patient know that it’s a safe space. Whatever you tell me, it’s a safe space and we’re going to work through it. And when you make people feel comfortable that they’re willing to share, you know what? The patient may say, “I had to pick between a $10 co-pay”—which may seem like nothing to us, but for some people it’s 30% of the money they have for that week, right? “I had to pick between that or my child’s formula.” Then we can start to have real, productive conversations about how to address those barriers.

Joseph Eron, MD: Colleen, how do you clinically evaluate who comes in? And if they’re viremic when you think they should be suppressed, how do you treat them?

Colleen Kelley, MD, MPH: It is just a conversation—understanding what’s going on, what’s preventing them from being able to take the medication—and it ranges from the ever-prevalent systems issues, which is the vast majority, to things like stigma. Not wanting to acknowledge that they need to take this HIV medication. And in very rare circumstances, drug interactions and things that lead to persistent viremia.

Clinically, the question is whether you need to test for resistance. A lot of that comes from the conversation with the patient, understanding you. Were they really trying to take their medication, or have they just been off? If they’ve just been off, I’m less concerned about resistance versus someone who really does sound as though they’ve been trying to take it, they’ve been getting it in their body on a somewhat consistent basis. Then I may pursue resistance testing at that point in time.

Joseph Eron, MD: It’s obviously a relatively expensive test. But on the other hand, even someone who is saying that they’re taking it intermittently, it’s information that you would need. If they said, “I just stopped it.” One of the things I’m impressed with is that people really feel like they are taking it, and then your pharmacist calls their pharmacy and they’ve only gotten 3 refills in the last 6 months. Sometimes they share that it is hard to comply and they forget.

Colleen Kelley, MD MPH: Oftentimes, it takes multiple conversations. After multiple attempts you learn, “I’m not really taking this.”

Joseph Eron, MD: Right, sure.

Ian Frank, MD: Sometimes it’s more effective to have a social worker or 1 of our nurse practitioners ask that question. Because the patients don’t want to tell me that they’ve done something that they know I’ll be a little unhappy about. They don’t want to disappoint me. Sometimes if somebody else asks the question in my practice, we are more likely to get the accurate information.

Joseph Eron, MD: We have a tablet in our clinic, and we try to collect the patient-reported outcomes, but I don’t know. Julia, if you could comment if you have any experience looking at patient-reported data in your practice, and how we should be using that more as part of our care. Do you have any thoughts about that? That’s not something we have built into structure DHR data. Patient-reported outcomes are not something that are routinely collected, but they’re so relevant. Even for the stigma barrier, particularly in places like the South that are the hardest hit, it’s really driving the epidemic to some extent. So yes, it’s really important.

Julia Marcus, PhD, MPH: Yes, We have a depression and alcohol screens, and we get a sexual history report. It’s social desirability or something where I’ll ask, “How many partners do you have?” When they do it on the computer they’re a little more likely to say 5 instead of 1. Not that it’s good or bad, but it helps to know in terms of risk and screening and that sort of thing.