Virological Failure and Incomplete Response in HIV

Segment Description: Joseph Eron, MD; Paul Sax, MD; W. David Hardy, MD; Eric S. Daar, MD; Ian Frank, MD, highlight considerations of what to do when patients with HIV present with virologic failure or incomplete virologic response.

Joseph Eron, MD: Let’s talk about something we actually don’t see that often, which is virological failure. I’m going to pass this over to Eric, because I want to make sure we get a mix here. So virological failure: What is your approach.

Eric S. Daar, MD: We don’t see it that often, fortunately. Resistance companies are going out of business because the treatments are so good. So we bring these people in when we do their viral load. If the viral load has gone up, we always want to confirm, and we always have to do due diligence, making sure they’re taking their meds consistently. And if they’re not, we’ll figure out why. Make sure there are no important drug-drug or drug-food interactions, which is still relevant with some of our more commonly used therapies, like cations, and things can affect absorption and even some of the new integrase inhibitors. So you do all that, and if you really think that they’re experiencing virological failure on a stable regimen, we do resistance testing. And the resistance testing will usually answer the question, because if they have no resistance, then there’s probably something going on with the way they’re taking their meds. And if they have resistance, then we design a new regimen. We don’t have a lot of—well, we probably don’t have any randomized controlled trial data for first-line failure on integrase inhibitors. But we have enough other data that we can probably extrapolate from. And the reality is that we know unequivocally that boosted PIs [protease inhibitors] with even recycled nukes, and certainly 1 active nuke is going to work. Boosted PIs with an integrase inhibitor is going to work. I think there are lots of options that people can switch to. The most important thing we need to do is figure out what went wrong because it’s so unusual to see it actually happen.

Joseph Eron, MD: Yeah, and there are so many steps where things can go wrong.

W. David Hardy, MD: The way I always look at this now is that adherence somehow got messed up. And whether it was that the patient lost interest, the patient had some sort of event in their lives and it became more chaotic or chaotic for the first time and really threw them off, or their insurance or their partner’s insurance was canceled and they were too embarrassed to talk about getting it set up again because they were trying to do something else. You know, there are a lot of little things in life events. It’s not the medication failing. The medication is failing to get inside the patient. Oftentimes, that is the problem.

Joseph Eron, MD: I think that’s right.

Paul Sax, MD: It’s so infrequent now to see someone who’s got detectable virus who’s actually taking their medications. That always makes you wonder if they are telling the truth. And here the practical thing to do is just call the pharmacies.

Joseph Eron, MD: Sure, and see when they’ve refilled it.

Paul Sax, MD: It’s incredibly accurate.

W. David Hardy, MD: That helps.

Ian Frank, MD: I’ll just say that when a patient tells you they’re taking all the medications, and they have quantifiable viral loads and no resistance.

Paul Sax, MD: Above, say, 200 copies/mL or so.

Ian Frank, MD: Yeah, above 200. And I think we should talk about the low quantifiable level viral loads and how we handle that. But I have found it helpful to have somebody else in my office talk to that individual, because the patient doesn’t want to disappoint me by acknowledging that they’re not taking their medication. They know that I’ve encouraged them to do it, and they don’t want to admit it. And so I always have our case manager talk to people to find out what are the obstacles in their lives that are really preventing them from being able to take the medication the right way. But checking pharmacy fill dates, which are often available in our electronic medical records now, is a beautiful and verified, validated way to assess adherence.

Paul Sax, MD: It turns out it’s unbelievably rare for someone to fill their prescriptions and then throw them away. It does happen. We had 1 person who famously did it in our clinic for a while, and his sister ratted him out to us.

Eric S. Daar, MD: There are pharmacies that do auto refills, which presents problems.

Joseph Eron, MD: Yeah, that can create a problem.

W. David Hardy, MD: A lot of them do.

Joseph Eron, MD: The auto refills, sure. But I think it is an excellent place to start. I mean, I’ve had patients kind of saved by a co-pay card, because they couldn’t tell me they couldn’t afford their co-pay, or saved by a pharmacist who took the time to help them put pills in a pillbox.

Paul Sax, MD: We had partnered with a pharmacy that was doing blister packs for us for years. They were terrific, but they, unfortunately, went out of business. So we now have to find a new blister-pack-producing pharmacy. These are incredible things: packages with the days of the week and all the pills they have to take, especially for people with complicated regimens.

W. David Hardy, MD: I like your point, though, Ian. The fact is that increasingly, I know in my practice, the patients I’m taking care of have very different backgrounds from what I have in terms of medical sophistication, medical literacy, all kinds of things, socioeconomic.

Eric S. Daar, MD: Most of them aren’t HIV specialists?

W. David Hardy, MD: Not really. And I agree. I am an authority figure for them, and they don’t want to disappoint me, so having them speak to someone else in the clinic who may look like them or come from the same community can actually be very revealing as to what’s really going on in their life. Because they may not tell me that they lost their job and that’s why they haven’t taken their medications. But they still show up for the clinic visit because they’ve got time on their hands. That’s not always a good thing.

Eric S. Daar, MD: And they’re using drugs and things like that.

W. David Hardy, MD: Right, they’re using drugs.

Eric S. Daar, MD: Or they’re embarrassed to be homeless.

W. David Hardy, MD: Right, exactly.

Eric S. Daar, MD: We’d be remiss, though, if we didn’t mention that as good as everything is and how easy it all seems, we still have these rare patients in our clinics, who we’ve been treating for 20 years, who have a lot of resistant virus. It’s just been very difficult. And I know we’re going to talk a little bit about some of the new drugs. But occasionally, we get to fall back to the lessons learned over a decade ago about how to manage people with truly multidrug-resistant virus.