Adherence

Adherence assessment is most successful when conducted in a positive, nonjudgmental atmosphere. Patients need to know that their provider understands the difficulties associated with taking an antiretroviral (ARV) regimen. Within a trusting relationship, a provider may learn what is actually happening with the patient's ARV medication regimen rather than what the patient thinks the provider wants to hear. Important questions to ask a patient who is considering ART may be found in Table 1. Table 2 suggests important questions for patients who are receiving ART.

Common reasons for nonadherence include the following: experiencing adverse effects, finding the regimen too complex, having difficulty with the dosing schedule (not fitting into the daily routine), forgetting to take the medications, being too busy with other things, oversleeping and missing a dose, being away from home, not understanding the importance of adherence, and being embarrassed to take medications in front of family, friends, or coworkers. It is important to look for these and other potential barriers to adherence. (See chapter Initial History.)

Evaluate the following:

	CD4 cell count
	HIV viral load (indicating the effectiveness of ART in suppressing viremia; an indirect indicator of adherence)
	Current drug list (including over-the-counter medications, vitamins, and herbal remedies); check for adverse drug interactions with ARV medications
	Pharmacy refill records

Assess adherence at each visit using questions such as those in Tables 1 and 2, and assessment scales such as those found in Tables 4, 5, and 6 (Appendix 1). Ask these questions in a nonjudgmental way and listen carefully to the patient to invite honesty about issues that may affect adherence.

Table 1. Important Questions to Ask Patients Considering Antiretroviral Therapy What is your attitude toward antiretroviral therapy? Do you believe that antiretroviral therapy is effective? What do you hope these medications will do for you? Are you ready to take the medication every day, around the same time each day? Are you committed and motivated to take the medication every day for the rest of your life? Who knows about your HIV status? What other medications are you taking: prescription, over-the-counter, herbals? Are you a morning or afternoon person? What is your daily routine, including waking and bed times? How many meals and snacks do you eat per day, and at what times? Do you use alcohol, marijuana, cocaine, or injectable drugs? If so, how much do you use and how long have you used them?

Table 2. Important Questions to Ask Patients Taking Antiretroviral Therapy Do you manage your own medications? If not, who manages them for you? What HIV medications do you take and what is their dosage? When do you take these? How do you remember to take your medications? How many doses of your HIV medication have you missed in the last 72 hours, last week, last 2 weeks, and last month? On a scale of 1 to 10, where would you say you are? A score of 1 indicates that you do not take your medicines right at all; for example, not every day or not at the same time every day; 10 indicates that you take your medications perfectly every day, at the same time every day. (Visual analog scales are also used to assess adherence; see Appendix 1.) If not a 10, what causes you not to be a 10? When are you most likely to miss doses? Do you have any adverse effects to from your HIV medications? If so, what are they? Are you comfortable taking medications in front of others? What is most difficult about taking your medications? How do you like working with your pharmacy?

The patient's self-report has been shown to be the most effective measure of adherence. Although, according to some studies, self-report of good adherence has limited value as a predictor of good adherence, self-report of suboptimal adherence should be regarded as a true predictor of poor adherence.

Before initiating (or changing) ART, it is important to assess the patient's readiness for ART. Patient factors that have been associated with poor adherence in the United States and western Europe include:

	Depression
	Active alcohol or drug use
	Low literacy
	Lack of social support
	Lack of belief in treatment efficacy
	Unstable housing
	Competing priorities (eg, housing, childcare, food, work)

Most of these factors are modifiable. Before starting ART, appropriate interventions should be made, and sources of adherence support should be identified to help patients overcome potential barriers to adherence.

It is important to note that sociodemographic variables such as sex, HIV risk factors, and education level generally are not associated with adherence. In addition, a history of substance or alcohol abuse is not a barrier to adherence.

Assess the patient's support system, and ask who knows about the patient's HIV status. Supportive family or friends can help remind patients to take their medications and assist with management of adverse effects. For patients who have accepted their HIV infection as an important priority in their lives, taking medications can become routine despite other potential adherence barriers such as alcohol or drug use.

Assess patients' willingness to accept and tolerate common adverse effects of ART. Patients may identify some adverse effects that they wish to avoid completely and others that they are willing to accept and manage; this may help in tailoring the selection of ARV medications to the individual patient. Describe strategies for the management of adverse effects before starting a regimen (see chapters Patient Education and Adverse Reactions to HIV Medications).

Before prescribing ARVs, some clinicians have their patients do adherence trials using placebo tablets or jelly beans to measure the patients' readiness to start therapy and their ability to adhere to a regimen. This trial allows patients to experience what a regimen will entail in real life, how therapy will affect their daily lifestyle, and what changes will be needed to accommodate the regimen. The shortcoming of placebo trials is that patients are not challenged with adverse effects as they might be with a true regimen.

For patients taking ART, it is important to assess adherence at every clinic visit. Tools such as those in Appendix 1 may be useful in predicting adherence. Adverse effects are a common cause of suboptimal adherence to ART. Continue to ask whether the patient has adverse effects from the ARV medications and assess his or her ability to accept and tolerate these. Work closely with the patient to treat adverse effects, and consider changes in ART if adverse effects are not tolerated. Continue to offer support to improve or maintain optimal adherence.

Start the ARV regimen only when the patient is ready. Starting it too early may result in poor adherence, failure of the regimen, and increased risk of ARV resistance. Comorbid conditions that interfere with adherence, such as mental health issues or depression, must be treated initially. It is important to consider the patient's preferences in selecting the drug regimen. The regimen must fit into the patient's daily routine, and the patient must believe in the potential success of ART. Simplifying the ARV regimen to the extent possible with once-daily regimens and the lowest number of pills, while maintaining efficacy and minimizing adverse effects, is important for maximizing adherence and avoiding pill fatigue. Starting ART is rarely an emergency, so taking time to identify the patient's wishes for care, make a thorough readiness assessment, select the ARV regimen, and plan for adherence support is important in maximizing the likelihood of treatment success. (See Table 3 for additional suggestions.)

Table 3. Strategies to Improve Adherence to Antiretroviral Therapy Establish readiness to start therapy Provide education on medication dosing Review potential adverse effects Anticipate and treat adverse effects Utilize educational aids including pictures, pillboxes, and calendars Engage family, friends Simplify regimens, dosing, and food requirements Utilize team approach with nurses, pharmacists, and peer counselors Provide accessible, trusting health care team Source: U.S. Department of Health and Human Services. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Table 16. October 10, 2006.

Patients who can identify their medications (in their own words) and describe the proper dosing and administration have higher adherence rates. Providing patient education before writing a prescription helps ensure adherence to ARV medications. Education can be provided in oral, written, or graphic form to assist the patient's understanding of the medications and their dosing. Basic information, including number of pills, dosages, frequency of administration, dietary restrictions, possible adverse effects, tips for managing adverse effects, and duration of therapy will help patients to understand their ARV regimens. Patients should understand that the success of ART depends upon taking the medications every day and that adherence levels of >95% are important in preventing virologic failure.

Close follow-up by telephone, clinic visits, or other contact with the patient during the first few days of therapy is useful in identifying adverse effects, assessing the patient's understanding of the regimen, and addressing any concerns before they become significant adherence barriers. Individualized interventions should be designed to optimize outcomes for each patient. Pharmacists, peer counselors, support groups, adherence counselors, behavioral interventions, and community-based case managers are useful in supporting adherence for the HIV-infected patient. Multidisciplinary teams that include nurses, case managers, nutritionists, and pharmacists, in which each care provider focuses on adherence at each contact with the patient, are extremely effective in supporting adherence.

Many physical devices can be used to support adherence. The following are simple, inexpensive, and easy to incorporate into the routine of the HIV patient:

	Medication organizers include pillboxes and medisets. These are available in several shapes and sizes to fit the needs of the individual patient. They can be filled weekly so that the patient can easily determine whether a dose of medication was missed.
	Reminder devices include alarm watches, beepers, or cell phone alarms. They are effective in reminding the patient when to take medications. Medication diaries may be used for the patient to record doses that were taken.
	Visual medication schedules: are calendars with pictures of the patient's medications on them to remind the patient to take the doses.

Interventions for successful adherence are an ongoing effort, not one-time events. Studies have suggested that adherence rates decline when patient-focused interventions are discontinued. Therefore, positive reinforcement at each clinic visit or contact is extremely important. Reinforce what the patient has done well and assist the patient in identifying and problem-solving areas for improvement. Whenever possible, share positive information about the patient's health, such as improvements in quality of life, CD4 cell count, and viral load, to encourage a high level of adherence.

Patients with mental health issues may have difficulty with adherence. In this population, it is particularly important to incorporate ARV medications into structured daily routines. Medication cassettes, reminder signs, and calendars have been very effective for these patients. Nursing care providers and family members may be instrumental in filling medication boxes or ordering prescription refills.

Adherence can be a challenge for young children who rely on parents and caregivers to provide their medications. Adolescents are more likely than younger children to have poor adherence. To improve adherence in this population, it is important to support the family. The Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection review some of the adherence issues and considerations for this patient population.

Health literacy is an important predictor of treatment adherence, particularly in low-income populations. Adherence interventions are necessary in this population to accommodate individuals who have difficulty reading and understanding medical instructions. Providers often fail to recognize this disability. In addition, adherence support is needed for patients who have difficulty navigating the health care system.

Early research has shown that the level of adherence in resource-limited countries is at least as good as that in resource-rich settings and that rates of virologic suppression are equivalent or better. Lack of access to a consistent supply of ARV medications, including financial barriers that may cause interruptions in treatment, appears to be the primary obstacle to adherence in resource-limited settings.