Navigating Through Virologic Failure in HIV Infection

Joseph Eron, MD: Something that we don’t see that much but we should probably talk about is virologic failure. Dan, I’d say that you are an expert in this. But, maybe experts get a little rusty when we don’t talk about it too much?

Daniel Kuritzkes, MD: Yes. The first thing is, how do we define virologic failure? What do we mean when we talk about virologic failure? I think it depends whether you’re just starting therapy or if you’re already on treatment. If you’re starting on treatment and you don’t see a log or 2-log reduction, a 10- or 100-fold reduction, in virus load over the first couple of weeks or month, there’s a problem. That should already be considered virologic failure. Somebody who never gets to being fully suppressed is also considered to be a patient with virologic failure.

If you are suppressed and you’ve been doing just fine, and now you start to have consistently detectable virus in the blood, that is probably virologic failure. If it’s very low numbers and it’s just above the threshold of detection in the assay, for complicated reasons that we won’t go into now, it’s probably not really virologic failure. But, if you’re up in the hundreds or thousands, then, certainly, you’ve failed.

And so, the question is, why did the patient fail therapy? Or, why is this therapy failing the patient? You really have to start by talking to the patient. You have to ask them, in as open-ended and nonjudgmental a way as you can, what their pattern of adherence is. What I usually do is ask, “In a typical month, how many times do you think you might miss a dose or forget to take a dose?” Not, “How many times aren’t you taking the medicine?” I like to find out, “What’s happened in your life, recently? Is there something that’s changed that’s made it harder for you to take your medicine?” Or, the patient may come in and say, “You know, I went to the pharmacy and they wouldn’t refill my drug.” Or, “But, I had lost it. So, I was only on 1 drug for the last 2 weeks.”

You really have to understand why they failed therapy. Once you understand why they failed, you’re going to be in a much better position to fix it. For fixing it, even though we often don’t see resistance any more, I would still get a resistance test just to know what your options are. Then, you have to determine whether it was just sort of a logistical issue that created the problem, or whether something about the regimen wasn’t suiting the patient. Maybe a different regimen would be better suited? A switch in regimen, even if there’s no resistance, might make a difference.

Joseph Eron, MD: Sure. But Eric, when we do get a resistance test and we see resistance, that’s probably a worthwhile time to discuss it with someone who has HIV expertise and manages the condition as a full-time job? What would you say?

Eric Daar, MD: I would agree. This is an unusual scenario. Young providers have very little experience in managing resistance. I think most people are aware of what Dan just talked about, but it is the most important thing. This person is an outlier. Something went very wrong and it’s not because the drugs weren’t potent.

Joseph Eron, MD: Right.

Eric Daar, MD: You really need to understand what went wrong before you take the next step. And, you need to involve an expert. We have a lot more data than we used to, to inform our decisions about managing people with treatment failure. There’s even new data, recently. Traditionally, it’s always been a boosted protease inhibitor path. Now, there’s even data that suggests that there may be a subset of people in whom you can use an integrase like dolutegravir, in a relatively simple regimen, for first-line failures with limited resistance. I do think you need to get expert input.

Joseph Eron, MD: Great. Is there anything else, in your practice, in terms of virologic failure? Are there any other points that you would make, in terms of succussing out why it happened?

Eric Daar, MD: No. The one thing I think about, that brings me back to the discussion we were having about switching—there are simple switches and there are complicated switches.

Joseph Eron, MD: Yes, good point.

Eric Daar, MD: We often do the simple switches. These people have done great on their first regimen. Now, maybe we move them from TDF [tenofovir disoproxil fumarate] to TAF [tenofovir alafenamide], or to a single tablet regimen. We do have a lot of people in our clinics who have had previous virologic failure. Now, they are stably suppressed.

One of the mistakes that young clinicians make is not considering what underlying resistance may exist before they think about the simple switch. So, dolutegravir/rilpivirine, for example, where we have this huge new dataset that really informs a switch decision, was studied in a very pristine population of people with no history of virologic failure. Currently, that is who it’s approved for. Before they do a switch, they need to think about previous failure and what underlying resistance patterns may exist. And, again, if you’re going to switch those people, you should rely on experts.

Joseph Eron, MD: Yes. I think that was really something—to get the old resistance test, and to try to get as much history as possible when you’re going to make a more complicated switch. I think that’s a really important lesson.

Colleen Kelley, MD: That requires us to go back to medical records, pull out those paper charts, and go through it, page by page, to get those old genotypes. But, we do have to do it.

Eric Daar, MD: It’s hard, yes.

Joseph Eron, MD: For someone who has 2- or 3-class resistance, they can sometimes be simplified. But, that’s really something that should be done with incredible care. And then, just to follow up, when you do make a switch in someone for reasons of virologic failure, even in relatively simple switches, I do tend to get the person to come back within that same kind of 4- to 6-week time point, to make sure it all went right, to ensure that they understood what I said, and to confirm that their viral load is either staying suppressed or is on its way back down. I think that’s important.

Transcript edited for clarity.