Solving the HIV Treatment Adherence Enigma

An Interview With Benjamin Young, M.D., Ph.D.

Executive Editor

Poor antiretroviral adherence is widely regarded as a leading cause of HIV treatment failure and the development of drug resistance. What we're less clear on is the precise level of adherence that a patient needs to observe in order to ensure treatment success -- and even that may be beside the point. Adherence, after all, is one of the most important end results of a complex interplay of factors affecting our patients, including the very nature of the HIV care they receive.

To better flesh out the importance of adherence in HIV care today, as well as the steps health care providers can take to increase the likelihood of treatment success in their patients, we spoke with Benjamin Young, M.D., Ph.D., the vice president and chief medical officer of IAPAC, the International Association of Providers of AIDS Care, as well as an adjunct professor at the Korbel School of International Studies at the University of Denver and an assistant clinical professor of medicine at the University of Colorado.

In light of the evolution of HIV treatment over the course of the past several years -- particularly the greater potency of antiretrovirals and, in the U.S., an overall trend of decreasing HIV drug resistance -- how important is adherence at all in the context of HIV care in the U.S. today?

I think that this is a really important observation, and question. Medications over the last 15 years have consistently, and persistently, improved: better side effects; lower doses; lower numbers of pills; and, perhaps more importantly, even with some of the more current regimens, less drug resistance. And, as you said, this has some important implications for pill taking and adherence.

Medications have gotten better, and the frailty of those regimens due to less-than-perfect adherence is less. Drug regimens are less likely to produce treatment failure and drug resistance. I think every provider is uncomfortable saying, "Go ahead and miss a few doses of pills," but our need to berate and stigmatize people for being less than perfect is less than it was five or 10 years ago.

But it still matters?

Yeah, of course. Missing life-saving medication is probably not the best thing. I mean, and that's stating the obvious. But I think that our margin of error now, and the acceptability of a margin of error, is greater than it was before.

The traditional benchmark for optimal adherence has been 95%. Your suggestion, then, is that maybe that's no longer the case? Maybe it's lower?

I think it is. One should remember that the 95% number -- really, the 95% mantra -- was generated by a study that was conducted in the late 1990s. That was a time when regimens were much more complex: more doses; shorter half-life of drugs; more side effects; and so on. In other words, regimens that really had a smaller margin of error, if you will. That number has stuck like a tattoo to our mind's eye, when we think about adherence and we talk to people living with HIV about their adherence.

There have been a number of well-defined studies since that ask what level of adherence is needed with modern antiretroviral treatments. When you do that, the optimal number actually isn't 95%. In fact, with some of the modern regimens, the number is considerably lower. It's almost like we're speaking heresy when we say that 90%, or 85%, or even 80% might be good enough. I don't think that anyone's saying that it's a good idea to miss one in five doses, but I think that it gives us an opportunity to change the dialogue and the language we have with patients about times when they may be a little more human, or a little less than perfect.

What do you mean by "change the dialogue"?

Well, for one, I think too often patients are afraid to admit their shortcomings. So, for example, if I had been taking care of a patient and I'd been hammering them about the 95% number, and they come in and over the last week they missed a bunch of doses -- maybe their calculated number is 80%.

Rather than saying, "You need to stop your treatment until you can get your act together," I can say, "Well, let's look at what's going on. Let's see how we can improve that, and ensure that the overall risk is lowered, and risk of failure is lowered. What are the interventions that we might entertain to do that?"

How can a clinician even really know whether a patient is adhering or not? Viral load monitoring -- you see a blip and you ask that question? Or should you be regularly checking in with a patient to make sure that they're taking their drugs?

I think that the answer's more the latter. In fact, I think that by the time you have a detectable viral load, the horse is out of the barn, as far as medications go -- the virus is out of the cell, if you will.

Monitoring for adherence should happen at multiple levels in the health care system. It's not just a dialogue that happens between patient and doctor; it's a dialogue that happens between patient and case manager; or patient and pharmacist; or patient and support team member; and so on. And it should happen, at some level, at most encounters.

I'm sure we'll touch on this later, but our association published evidence-based guidelines around adherence to medications and care. One of the most strongly rated recommendations was that we should routinely ask all patients about self-reported adherence.

This means that we should be asking people about how they take their pills, understanding that there's reporting bias and error. But the people who are having difficulty will tell you -- at least, some of them will. And that's a reason to act. Conversely, even people who are doing well -- I'm sure that would be an opportunity to reinforce good behaviors.

This sounds like it's going far beyond our traditional understanding of what adherence is all about: "Hey, make sure you take your meds."

Right. It's important because, in fact, there are some studies that suggest poor adherence in those self-reports eventually predicts virologic failure, even if the viral load is suppressed at the time of that inquiry.

Again, viral breakthrough is a late marker of poor adherence. What we want to be doing is to be ahead of the curve and try to do something about it before there's a problem.

What are the steps that a clinician can even take to be on top of a person's adherence? Is this literally just a matter of the health care provider, or the case manager, or some combination thereof, having this regular schedule where they check in and directly ask a person whether they're taking their meds?

There are lots of other interventions. I think it distills back to this idea of individualizing care -- in other words, understanding who the individual is. At one level, understanding what their frailties are, what their risks are. People, for example, who have housing and food security problems, people who have mental health problems, those are people who may be at greater risk. It doesn't mean that they are having adherence problems, per se. But we need to know the warning signs so that we can offer a step -- and then, if necessary, offer greater degrees of support.

Pharmacy refill information is critically important, and it's right in front of us. Pharmacies can provide that information, but don't often communicate it well down the totem pole of care providers. Making sure that information is communicated -- not just to the prescriber, but perhaps to case managers, perhaps to other members of the health care team -- can provide an opportunity for assessment and decision-making long before the patient gets into a lot of difficulty.

Whose responsibility is it to achieve this level of communication?

I think that the answer to that is a very organic one: It depends on what the structure of the care team looks like. That differs from community to community. At a minimum, it's the doctor of the patient -- or the care provider of the patient; many care providers are not physicians.

I think it's an opportunity to strengthen the communications across the care team. Sometimes that's housed in one place; sometimes it's not. In our community in Denver, it's actually housed in multiple places. It can be a challenge to try to coordinate information about a potential warning sign on adherence between a pharmacist, a case manager, a care provider and the patient. But making sure that some sort of dialogue happens around that, I think, is important. And strengthening those communication ties is an opportunity to make it work better for people.

Is that realistic in the context of where we are with health care funding and the general fragmented nature of HIV care generally? We have exactly what you just described: situations where a person is going to a regional clinic to see their doctor, nurse-practitioner or whomever, and that's where they get labs done, that's where they have their three-month check-in, and that's where their meds are prescribed. They've got a case manager at a community-based organization -- maybe nearby, maybe not so nearby -- that checks in with them periodically just to see how they're doing. And then they go to Walgreens to actually fill the prescription.

That's a lot of places, and a lot of potential for cracks in that effort to keep track of the patient and make sure they're OK and taking their meds. But on the flip side, if everybody takes individual responsibility for staying on top of care and ensuring patient adherence, there's potential for a lot of overlap that could end up frustrating a patient.

Yeah. I think this is a story that requires individualized tuning of messages and the messengers. To your first point: It's important to understand that we shouldn't be talking about yet another unfunded mandate to care providers who are already stretched to their limits, and patients who have complex lives and busy activities.

But this can be done inexpensively. If anything, we should be learning lessons from all of the efforts that have been made in East Africa that allow task shifting of responsibilities across a broad spectrum, or bandwidth, of care providers.

The other thing I think that emerges out of East Africa, particularly, is this notion of social investment: The more that the patient understands that there are people invested in their health, the more likely it is that they will stay engaged in care, and the more likely it is that they'll continue taking their medicines when appropriate.

The other piece of it is a bit of redundancy, but it's important: engagement with patients. These organic networks, if you will -- it could be as simple as a phone tree, or an email list with the patient's permission, which allows people to communicate across that network that says, "John Doe missed an appointment," or "John Doe missed a refill. Can we do something to intervene?"

I've seen this work in clinics in rural villages in East Africa. If it can happen there, I'm sure it can happen here in the States.

You referred a little earlier to your organization's guidelines on this sort of thing. You're the chief medical officer of IAPAC, which, last year, put out some pretty comprehensive adherence recommendations. What are the key takeaway points from those guidelines?

Well, the IAPAC guidelines were published last year in Annals of Internal Medicine. It was the result of an international effort to compile the best evidence around improving both engagement in care and adherence to antiretroviral treatments. There are very specific recommendations, with grading as to the strength of the recommendation and the quality of the data.

I think it's important to understand that there is science behind this. In some places, the science is not as robust or as deep as we might want it to me; in fact, I think it's stunning, when we think about the 30 years of the epidemic, that we have really only a few hundred quality publications on the subject. So, as important as adherence is, there's room for a lot more thoughtful science and learning.

But in terms of how do we do better at this, our guidelines speak to improving education and counseling around adherence. Ironically, some of the best data on this are about the use of communication technologies -- using your cell phone and text messaging to remind people about appointments or taking their medicines; there's actually good data about that -- but we don't deploy that on a regular basis here in the States. And I think, again, there are opportunities to learn on that.

The idea is that at the community level, but also at the individual level, there are interventions that can be deployed to improve the patient's knowledge base about why adherence is important -- what kind of interventions we can do to operationalize those education points -- as well as ways to communicate the goals about taking medications or making other appointments. We can improve how those ultimately are acted on by the patients.

There are strong recommendations over providing education about antiretroviral therapy. There are strong recommendations about providing one-on-one support and adherence counseling to people.

And by "education about antiretroviral therapy," do you just mean explaining how the drugs work?

Pretty much, yeah. In other words, the better people understand why they're taking medications and how they work, it turns out that actually helps people take the pills. And conversely -- this is important data that has also emerged -- if people don't understand that there's a reason why they take these things; if people don't understand what to do if there's a side effect; if people don't understand, or don't believe, that medications will help; they tend not to take them.

Again, both the message and the messenger are important. We have to educate people that these medicines work, they are nearly always well tolerated, and they will save your life. If people understand that, if they actually believe that -- how to get people to believe it is sort of a separate conversation -- they are more likely to take them.

There's a really strong educational component to this. There are also very specific guidelines on collecting information -- again, as we said -- about self-reported adherence routinely from patients, and getting pharmacy refill data when appropriate. These are strong evidence-based recommendations. Those things should be implemented both abroad and here in the United States.

The guidelines have recommendations about adherence in special populations of people; it's mostly to highlight the fact that different populations of people and different individuals may have individualized needs.

Also, this is an important point that is made by the evidence-based guidelines: It doesn't have to be the doctor. It doesn't have to be the prescriber that mainly does these interventions -- in fact, there are strong recommendations that the nurses or community-based counselors can provide adherence counseling, even in under-resourced areas. And "under-resourced" doesn't only mean Eastern Africa; it could mean rural United States. Case managers also can address some of these needs, as well.

The point is that -- although perhaps it's articulated in more nuanced, "guidelines" terms -- it takes a village. It takes a village of people working together, each working in their own spectrum of responsibilities, to improve adherence and decrease adherence risks in people.

For the most part, it sounds like these guidelines are focusing on the need for better communication within the health care community and with patients directly. How much of this is also about improving infrastructure, or using specific tools to monitor -- or to intervene in hopes of improving adherence?

There is a need for institutional improvements. Some of that has to do with the ways that institutions or care teams communicate to each other. These are opportunities where electronic health records or practice management systems may help. For example, a system that flags a patient who misses an appointment, or misses two appointments, or misses a pharmacy pickup -- exploiting these kinds of calendars or reminder systems; "John Smith hasn't been in the clinic for three months," or six months, whatever the prescribed interval was -- and then using that to notify the team. Some of this happens within the health care system itself.

I should point out, though: There are things that happen at the communication level between the provider and the patient, and this is where there is ample room for improvement. A lot of times, when we talk about this, the conversation that we have about pills and adherence to other medications is done in ways that can be stigmatizing, and therefore make the patient less likely to stay engaged in care.

To this point, our group published recommendations -- based on an expert panel -- about what language we should use to ask people about their pill taking. Medical doctors don't follow the science of psychology and linguistics very much, but there are smart people out there addressing this point in peer-reviewed literature.

We published a short paper this year that was authored by Rivet Amico in Connecticut that ultimately distills this down to a very simple phrase, in terms of asking people about their pill taking. It says, in quotes: "In the last 30 days, how good a job did you do at taking your HIV medications in the way you were supposed to?"

The words, the adjectives, the verb tense are things that experts actually adjudicated on. For example, the phrase "30 days," instead of "one week" or "one month": There was expert opinion rendered on that number. There was expert opinion on the phrase "how good a job," as opposed to some other taxonomy or language.

It's learning how to ask the questions. It's learning how to respond to the answers. There are opportunities to further fine-tune, and to thoughtfully and scientifically go about the process of asking people about their pill taking. There are certainly opportunities to further improve this, as we move forward into the next decade of care.

Our entire conversation so far has focused on people who are taking antiretroviral therapy and ensuring that they remain in care; that they take their meds as optimally as is possible and reasonable. Are there cases in which, because of adherence concerns, clinicians should reconsider even prescribing therapy in the first place, at least for a little while?

What if a person does not have stable housing? What if they have a substance use issue? What if they are in and out of prison? Maybe they shouldn't be starting treatment yet.

That's a bunch of really important points. There's a lot more to this than just pills. When we think broadly about health, we have to appreciate that for some individuals, taking a pill, or even HIV itself, may not be the most pressing health issue. The person who is homeless, the patient who is actively suicidal, the patient who has active substance use disorders, may have more pressing short-term health issues. That doesn't mean necessarily that HIV becomes secondary or tertiary, but it needs to be placed in that context.

So, at one level, this means that we need to be thinking very broadly about how we define "health" and the health goals for individuals.

I think it's important to say that people who are marginally housed, or have mental health problems, aren't necessarily going to be nonadherent. But the person who says, "I don't want to take pills," is probably going to be nonadherent. That could come from known risk factor groups, or just from an individual who doesn't yet believe that medicines are necessary or will be helpful.

It means that we have to think about adherence from the very broadest sense. That means: Are people able to get to health care? Are they willing to be in health care? Do they have other barriers to entering health care or staying in health care? Ultimately, I think adherence at that level actually is critical -- and, in fact, in my view it supersedes the decision about who gets a pill or doesn't get a pill.

When I think about adherence, I think about the roughly 20% of Americans who are not yet diagnosed with HIV. I think about the additional 20% who are diagnosed, but have not crossed the threshold of care. I think about the additional 20%, yet again, who have been in care once, but haven't been back within 12 months. Adherence to that part of medical care is -- certainly for those individuals, but in the community at large -- a huge, unmet need.

When we think about this at the community level, we need to be thinking about those patients as much as those who are in care and having difficulty initiating or staying on treatment.

It sounds almost as much of a mental and psychological health issue as it is a clinical, biological health issue. That's traditionally been an area that's been avoided in clinical care.

Yeah, absolutely. I think that we have made enormous strides in HIV medicine in the last couple of decades with these biomedical interventions -- that is, learning about the pathophysiology, learning about CD4 counts and plasma viral loads, and learning to discover, find and evaluate new molecules that eventually become drugs and treatment recommendations. We have done a pretty good job, certainly since the early days of the epidemic, in creating community support networks, and finding the finances to strengthen housing and food banks and such. But most of those were born and evolved in a time of plague, in desperation.

I worry, in a modern era -- where people who have access to care don't die of AIDS, and AIDS isn't on the cover of Time and Newsweek -- that the interest to provide the continuing support, or to integrate HIV care into the possible support systems for housing and food security on one hand, and mental health care on another, may be waning. And those provide -- or are going to provide -- very substantial challenges for us.

I mentioned at a conference in London just a few weeks ago that the leading cause of death in my panel of patients -- people I care for in a small city in the Midwest, in Colorado -- is no longer AIDS-related. The leading cause of death is not cardiovascular disease and cancer; the leading cause of death is related to mental health.

When we look at large cohorts, both in North America and in Europe, trauma and suicide now are the third- or fourth-leading cause of death in populations of people living with HIV. That means that we really need to redouble those efforts. It requires a culture shift from the urgency and the acuity of death and illness from AIDS-related complications and AIDS-related cancers to thinking about a longer game plan of keeping people in care, keeping people healthy, and ultimately allowing them to return to normal lives, jobs, and paying taxes to keep government happy -- if anything keeps government happy.

And the key to getting there is what? For each person to do their part?

I think so. To borrow the cliché, it does take a village. We need to continue to keep our eye on the ball, even if the ball is less well funded, even if the ball isn't quite as bright and shiny as it was in the past.

It also means that we need to be innovative and creative. I think many of the solutions are out there. But we can't continue doing things the way we have in the past.

The prognosis of people here in North America has improved to the point where we are talking about normal life expectancy. I'll say it again: Achieving normal life expectancy requires that we think about long-term health and long-term engagement in care, to deliver on the promise of everything that drug discovery and tens of thousands of people's participation in clinical trials has offered us.

To do that, it means that we have to change from an operational foundation of death, dying and plague to an operational foundation of prevention and long-term engagement in care -- and all of the infrastructure and finances that go with them.

I think that's a good note to end on. Thank you, Dr. Young.

This transcript has been edited for grammar and clarity.

Myles Helfand is the editorial director of and

Follow Myles on Twitter: @MylesatTheBody.