Breaking Barriers to Medication Adherence in HIV: An Interview With Robert Gross, MD

Medscape HIV/AIDS

Robert Gross, MD, Shira Berman

Aug 05, 2013

Editor's Note: Adherence to HIV medications is key to improved treatment outcomes, but a variety of barriers can impede good adherence in different populations. This issue was one of many topics discussed during sessions at the 8th International Conference on HIV Treatment and Prevention Adherence, held in June 2013 in Miami, Florida.

In an interview with Medscape, Robert Gross, MD, Associate Professor of Medicine at the University of Pennsylvania Perelman School of Medicine in Philadelphia, reviewed some of the key barriers to medication adherence in HIV-positive patients and discussed strategies for overcoming these barriers in different patient populations.

Medscape: One of the panel discussions at the conference focused on how clinicians can address barriers to medication adherence in people living with HIV. Of all of the barriers to care, why is this one so important?

Dr. Gross: Barriers to care can occur at any step. There could be barriers to getting tested and determining the need for care. There could be barriers to linkage -- finding a provider who knows how to deliver effective care. There could be barriers to retention -- the patient staying in care and the clinic keeping the patient in care. And then there's the issue of adherence to therapy. This is so challenging to address because there is no one barrier that interferes with medication adherence. Although there are certain universalities regarding adherence, barriers to adherence can play out very differently within different populations.

For example, one person in the audience talked about seeing a patient reading from a bible in the waiting area. The physician learned later that the patient was actually illiterate and was flipping through pages of the bible as part of a prayer mechanism. The lesson here was that it is important to be aware of the cultural setting and recognize the ways in which providers can be misguided in trying to help patients because they mistake the cues that patients might be sending.

Also, an individual patient can have multiple barriers and have multiple different needs for overcoming those barriers. This is why interventions that work tend to be those that are tailored to each individual's problems and reasons for nonadherence. It is unlikely that we will have a silver bullet for improving adherence across the board. It's really going to need to be tailored to each individual's barriers and characteristics.

Learning From Others' Experience

Medscape: The title of the panel was "Tips for Addressing Adherence With Patients."^[1] What were the key takeaways tips that panelists shared from their own experiences?

Dr. Gross: What came across strongly from all of the panelists is that being nonjudgmental is very important -- and very difficult for providers to do. It's difficult to have a patient who is engaging in a behavior that is risking her health and yet not have an emotional reaction that comes across as negative or as demeaning to the patient.

We talked about how providers can instead try to be positive about the good things the patient is doing. For example, if he took 2 doses in the month, try to build off of that rather than focusing on the other 28 missed doses.

Patients are aware of their own nonadherence. It's not simply that they are forgetting doses but more that they're avoiding doses or they're not recognizing that they're forgetting doses. They're not necessarily going to want to talk to someone about that if they feel they're being judged for their behaviors.

One point that was emphasized by Dr. Ira Wilson, who facilitated the session, was the importance of using open-ended questions. This lets the patient express himself and gives him an opportunity to talk about the challenges he is facing.

For example, asking questions such as "How are you doing with your medications?" and "How are the medications working for you?" opens the dialogue to a much more productive discussion and allows for a better give-and-take conversation about the kind of help the patient might need. Asking open-ended questions is not something that is easy for doctors to do, but it is something that is very important for us to try to implement.

Less Is Not Necessarily More

Medscape: What about things we thought might work but don't? In one presentation from the meeting, they showed that less frequent, intermittent dosing does not necessarily lead to better adherence in patients on preexposure prophylactic antiretroviral medication.^[2] This seems almost counterintuitive; you would think that a regimen that requires fewer doses would be easier to adhere to.

Dr. Gross: Yes, it is counterintuitive, but we've learned a lot about medication adherence and can now understand why fewer doses might not always be better.

It seems relatively clear that more than 1 dose per day is a relative barrier to adherence, and 1 dose per day is preferred over more doses per day. But fewer doses per week may not be an improvement over a daily dose because of the way a patient's daily cycle functions -- doing something 3 times a week may be harder to remember than something you do daily.

If you are self-administering something once a week or once a month, it's not necessarily better than a once-a-day administration because you've lost that reminder system that goes along with a routine: "Every day I brush my teeth, every day I eat breakfast, every day I take my medication." There aren't too many things that we do weekly that we can link to. This is an issue that will come up as we develop longer-acting drugs, and it's not at all clear that less frequent self-administered dosing will improve adherence.

What does seem likely is that if dosing is less frequent, such as once a week or once a month, and it is self-administered, you can build interventions that are more intensive than interventions that would need to be delivered every day. Because they are delivered so infrequently, more intensive interventions might hold more promise of being cost-effective, implementable, and scalable than they would be if we were trying to target more frequent dosing.

And, in fact, this may turn out to be necessary when it comes to longer-acting drugs that are taken less frequently. For a drug for which the dosing is near its half-life, any one missed dose may be more damaging. Let's say you are on a once-weekly treatment. Your adherence rate might need to be 90% in order for that treatment to work; but if you are on a daily treatment, it might be that only an 80% adherence rate is needed. The daily schedule allows for more missed doses because of how drug dosing is related to the pharmacokinetics. There is no simple answer here; an optimal dosing schedule for each drug is ultimately going to be related to the potency of the drug, its pharmacokinetics and pharmacodynamics, and the adherence rate.

Adherence in the "Well" Patient

Medscape: It would seem to be easier to implement therapy and maintain higher medication adherence rates in patients who are symptomatic. What are the challenges for HIV-positive patients with higher CD4 counts who are well?

Dr. Gross: Lack of symptoms is a relative barrier to adherence, but it's not specific to HIV. We've seen this in other areas -- patients who have high blood pressure or high cholesterol and have no symptoms have very low rates of adherence to medication.^[3]

The problem is that any one barrier may or may not exist for an individual. There are individuals who have high CD4 counts who are very committed to therapy. They buy into the idea of therapy. They are good with their routines, and they have no problem with adherence. Then there are people with very low CD4 counts. They are very sick. They are symptomatic from their HIV disease. If they take their medications, they do better, and yet they don't have good routines to help them stick to a schedule and take their medications.

Paying attention to the individual patient's situation is important. This is one of those barriers to be aware of, but we should be careful not to assume that people with high CD4 counts who are healthy are not going to take their meds and that people with advanced disease will necessarily be more adherent.

In part, it depends on the trust that the patient builds with the provider, how committed the patient is, and whether they believe in the advice that the provider is giving. Studies have shown that believing in conspiracy theories and mistrusting the medical establishment can serve as a barrier to adherence.^[4,5] Uncovering some of those beliefs and trying to establish more of a rapport, more of a trust in the provider, is equally important.

Treating Depression to Improve Adherence?

Medscape: One presentation found a high rate of comorbid depression in HIV patients and an even higher rate of multiple concurrent psychiatric conditions.^[6] How does psychiatric illness affect adherence to medication?

Dr. Gross: Disordered thinking is certainly a relative barrier to taking medication, and depression is a known barrier to adherence.^[7] But there are also other issues at play in these patients. The National Institute of Mental Health is funding research on patients who have concurring mental illness and HIV, focusing on: (1) how HIV drugs affect mental illness; (2) how mental illness affects HIV drugs; and (3) how the two interact. Does taking a mental health drug affect drug concentrations of the HIV drugs, and vice versa? It's a very complicated population to care for, and a lot of patients with mental illness are doing well, but it is certainly an added challenge.

Of note, there is not a lot of evidence that treating the depression improves adherence. We developed an intervention program called "Managed Problem Solving"^[8] (and gave a how-to at the conference on implementing the intervention in the clinic.^[9]) We showed that the intervention improved adherence and improved depressive symptoms, but they were independent phenomena, and one did not affect the other.

It's not clear to me that the treatment of depression as a way to improve adherence is necessarily going to result in better outcomes. Dr. Steven Safren published a paper last year^[10] showing that an intervention targeted to depressed people with HIV can improve the depression, but the improvement did not result in sustained improvement in adherence or have any effect on virologic outcome.

Literacy is another example where we have assumptions about how it affects adherence that may not be true. Dr. Seth Kalichman presented the details of an intervention that used pictograms to help people who are illiterate understand the disease and the importance of medication adherence.^[11] But it didn't work -- those with lower literacy showed little if any benefit. Clearly, it's not just about the information being conveyed to them, it's also related to all of the other complications that low literacy creates in their lives.

We have to be careful not to conflate the mechanisms by which each of these barriers results in treatment failure.

Learning From the Older Patient With HIV

Medscape: One of the final sessions at the conference focused on the management of older patients with HIV and the importance of identifying engagement challenges unique to this population.^[12] Are there issues specific to medication adherence as well in this population?

Dr. Gross: It's interesting -- once we get past the problem of not testing older people for HIV, we find that they actually have higher rates of treatment success, higher rates of adherence, and lower rates of discontinuation.

This may have something to do with the stability of life as people get older. These patients are living much less chaotic lives. They are more likely to have established routines. And we already know that routines help patients stay adherent. Trying to help people establish routines and helping them find patterns in their lives is probably a good place to focus for younger patients who are struggling with adherence.

Everybody has some kind of pattern in their life. It might be harder and more challenging to find that pattern, but once you find it, you can link medication taking to it. That's something we can learn from the success of the older folks.

References

1. Wilson IB, Bassett I, Giordano TP, Gross R, Nettles MJ. Provider panel -- tips for addressing adherence with patients. Program and abstracts of the 8th International Conference on HIV Treatment and Prevention Adherence; June 2-4, 2013; Miami, Florida.

2. Haberer J. Factors influencing adherence behavior for daily and intermittent regimens of PrEP among MSM in Kenya. Program and abstracts of the 8th International Conference on HIV Treatment and Prevention Adherence; June 2-4, 2013; Miami, Florida. Abstract 68.

3. Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005;353:487-497. Abstract

4. Bogart LM, Wagner G, Galvan FH, Banks D. Conspiracy beliefs about HIV are related to antiretroviral treatment nonadherence among African American men with HIV. J Acquir Immune Defic Syndr. 2010;53:648-655. Abstract

5. Gaston GB, Alleyne-Green B. The impact of African Americans' beliefs about HIV medical care on treatment adherence: a systematic review and recommendations for interventions. AIDS Behav. 2013;17:31-40. Abstract

6. Gaynes B. Psychiatric comorbidity in depressed HIV-positive individuals: common and clinically consequential. Program and abstracts of the 8th International Conference on HIV Treatment and Prevention Adherence; June 2-4, 2013; Miami, Florida. Abstract 124.

7. DiMatteo MR, Lepper HS, Croghan TW. Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence. Arch Intern Med. 2000;160:2101-2107. Abstract

8. Gross R, Bellamy SL, Chapman J, et al. Managed problem solving for antiretroviral therapy adherence: a randomized trial. JAMA Intern Med. 2013;173:300-306.

9. Gross R. An orientation to the MAPS problem-solving counseling intervention to promote ART adherence. Program and abstracts of the 8th International Conference on HIV Treatment and Prevention Adherence; June 2-4, 2013; Miami, Florida. Science to Practice Session.

10. Safren SA, O'Cleirigh CM, Bullis JR, Otto MW, Stein MD, Pollack MH. Cognitive behavioral therapy for adherence and depression (CBT-AD) in HIV-infected injection drug users: a randomized controlled trial. J Consult Clin Psychol. 2012;80:404-415. Abstract

11. Kalichman S. HIV treatment adherence counseling interventions for people living with HIV and limited health literacy. Program and abstracts of the 8th International Conference on HIV Treatment and Prevention Adherence; June 2-4, 2013; Miami, Florida. Abstract 28.

12. Alcaide ML. Aging and HIV comorbidities: a challenge for engagement in care. Program and abstracts of the 8th International Conference on HIV Treatment and Prevention Adherence; June 2-4, 2013; Miami, Florida.

Source