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Dealing With the Obstacles in Adhering to Highly Active Antiretroviral Therapy

Hubbard, Minda, MSN, ANP-C

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Journal of the Association of Nurses in AIDS Care: January-February 2006 - Volume 17 - Issue 1 - p 18-25
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Abstract

Although patient adherence to treatment is difficult to achieve in most chronic diseases, both the obstacles to adequate adherence and the consequences of inadequate adherence are magnified in HIV infection (Williams, 2001). Successful long-term treatment of HIV/AIDS requires at least 95% adherence to highly active antiretroviral therapy (HAART) if the emergence of drug-resistant viral strains is to be avoided (Ickovics et al., 2002). This very demanding requirement differentiates the problem of adherence to HIV therapy from that of other chronic conditions (Chesney, 2003). Because of the degree of cross-resistance exhibited by HIV viral strains, patients with inadequate adherence run a high risk of developing resistance not only to their current regimen but to many other agents as well, in some cases precluding future treatment options. In addition to meeting an extremely stringent requirement for adherence, patients infected with HIV must struggle with regimens that are among the most complex and demanding of any currently administered (Chesney, 2003). Consequently, many patients are unable to be fully adherent, and adherence tends to wane over time (Ickovics et al., 2002).

A number of models have been suggested to help improve patient adherence (Loughlin & Jensen, 2000; Williams, 1999; Williams, 2001). However, regardless of the approach selected, any program to improve adherence to HIV treatment should include the ability to assess adherence issues and devise a multifocal strategy that targets the patient, the provider, and the treatment regimen. Because nurses are most familiar with the problems and challenges of adherence (Williams, 1999), they are uniquely qualified to assist patients in achieving and sustaining adequate adherence to HIV treatment. There are a number of important issues surrounding patient adherence to HAART, for example methods to assess adherence and the relationship of adherence to biologic outcomes. However, the primary purpose of this article is to posit that, because of their holistic perspective, nurses are uniquely qualified to identify the various obstacles to full adherence and assist patients with these issues.

Obstacles to Patient Adherence

Numerous factors combine to make adherence to HIV therapy particularly difficult. These factors may relate to the disease, the patient, the provider, or the treatment regimen (Table 1) (Ammassari et al., 2001; Ammassari et al., 2002; Williams, 1999). Each of these factors is discussed below, with particular focus on how each impacts adherence to HAART.

Table 1
Table 1:
Factors That Contribute to Nonadherence to HAART (Ammassari et al., 2002)

Disease-Related Factors

Adherence rates are consistently lower for long-term, chronic illnesses and for asymptomatic conditions (Graney, Bunting, & Russell, 2003). In the case of asymptomatic HIV patients, the only immediate perceived effect of HAART may be a deterioration in health status and well-being as a result of medication side effects and disruptions in daily routine (Williams, 1999). Conversely, adherence is frequently greater in patients with advanced disease. For these patients, the improvement in disease-related symptoms resulting from controlling viral replication on HAART often outweighs the adverse effects of treatment (Williams, 1999). Chronic diseases require long-term therapy; in the case of HIV infection, it is likely that treatment could be required for the remainder of the patient's life. Over time, even the most motivated patients find it increasingly difficult to remain adherent (Ickovics et al., 2002).

Patient-Related Factors

Factors associated with socioeconomics including age, race, economic level, and the availability of housing are inconsistently associated with nonadherence to HIV treatment, as are psychological factors such as depression (Ammassari et al., 2002). Substance abuse (cocaine, marijuana, amphetamines, sedatives) and moderate to heavy alcohol consumption have been linked to nonadherence, whereas an individual's HIV risk factors have not (Ammassari et al., 2002; Tucker, Burnam, Sherbourne, Kung, & Gifford, 2003). Unless the patient has reached acceptance of the diagnosis, the medications serve as a negative reminder of one's HIV infection (Graney et al., 2003). Believing in the efficacy of the medication and the presence of social support systems has been positively related to adherence to HIV therapy (Ammassari et al., 2002; Chesney, 2003). Cultural or religious values, beliefs, and practices can impact adherence and clinical care. Examples include ritual fasting, health beliefs, the tendency to say “yes” out of respect despite lack of genuine understanding of communications with a health care provider, fatalistic beliefs, and the involvement of family members versus self-reliance in successful maintenance of medication regimens (Flores, 2000; Ka'opua & Mueller, 2004; Melbourne, 1999; Murphy, Roberts, Hoffman, Molina, & Lu, 2003). Certain patterns of behavior have also been linked to nonadherence in patients with chronic, asymptomatic diseases, including not filling prescriptions, forgetting a dose, taking incorrect doses, stopping medication too soon, and self-regulating the regimen to manage side effects (Ammassari et al., 2001; Chesney, 2003; Trotta et al., 2002).

Provider-Related Factors

In general, providers do not accurately predict which patients will be adherent to treatment or assess the adherence of patients already receiving treatment (Gross, Bilker, Friedman, Coyne, & Strom, 2002; Paterson et al., 2000). Lack of expertise, time constraints in busy clinic settings, and patient reluctance to disclose nonadherence may all be contributing factors. Both overestimation and underestimation of patient adherence have significant consequences. Incorrectly assessing a patient as adherent results in a missed opportunity to address the problem and provide necessary support, whereas incorrectly predicting that a patient will be nonadherent may result in treatment being withheld or delayed (Gross et al., 2002).

Effective collaboration between patients and providers is cited as a factor in adherence. A trusting, supportive relationship positively affects adherence. However, the perception of the provider as being judgmental can impede effective collaboration (Graney et al., 2003; Haile, Landrum, Kotarba, & Trimble, 2002).

Treatment-Related Factors

A variety of aspects related to HIV treatment can impact adherence including the complexity of the regimen, side effects associated with HAART, and the use of complementary or alternative therapies.

As observed with other chronic diseases, the complexity of the HAART regimen affects adherence to treatment. Several factors that contribute to the complexity of HAART include dosing frequency, pill burden, dietary instructions, convenience, and the ability to incorporate a treatment regimen into the patient's daily routine. The association between the number of doses per day and patient adherence is well known, with adherence declining as dosing frequency increases (Claxton, Cramer, & Pierce, 2001; Graney et al., 2003). In clinical studies, high pill burden is often reported as a reason for missing or discontinuing HAART (Trotta et al., 2002). In fact, a meta-analysis of clinical studies demonstrates that low pill burden has consistently been associated with decreased viral load and improved adherence (Graney et al., 2003). The extraordinary difficulty of incorporating many HAART regimens into everyday activities also poses a significant obstacle to adherence, with treatment-associated food restrictions being especially problematic for many patients (Chesney, 2003).

Side effects associated with HAART include transient events such as fatigue, diarrhea, and nausea, as well as longer lasting effects such as metabolic disorders and neuropathy (Chesney, 2003). In general, adherence to any therapy declines with the emergence of side effects. However, this is particularly true in the case of HAART, in which side effects are a primary cause of nonadherence and account for more regimen changes than do treatment failures (Ammassari et al., 2001).

As patients live longer with HIV, long-term drug exposure has become a problem of increasing concern because of metabolic complications. As experience with protease inhibitors (PIs) has increased, it has become apparent that these agents are often associated with metabolic abnormalities that may pose significant health and social problems for patients. Peripheral fat atrophy, central fat accumulation, dyslipidemia, glucose dysregulation, osteoporosis, and osteopenia have been observed in a large segment of patients receiving PIs (Briggs & Drabek, 2001; Moyle, 2002). These abnormalities can result in potentially serious hepatic, cardiovascular, and skeletal health problems (Briggs & Drabek, 2001). For many patients, however, the “buffalo hump” and other distortions in physical appearance that can be part of this metabolic syndrome are even more distressing (Chesney, 2003). The effort to reduce hyperlipidemia and/or hypertriglyceridemia may require alterations in HIV therapy or the addition of cardiovascular drugs such as statins, necessitating new adjustments and increased pill burden for patients (Moyle, 2002). Further complicating treatment is the fact that many PIs, as well as delavirdine, use the same metabolic pathway (P450 isozyme CYP3A4) as most statins; therefore, concomitant use of these drugs may result in potentially dangerous drug interactions (Briggs & Drabek, 2001; Dubé et al., 2003; Kirton, 2001).

Although figures vary depending on the population sampled, studies indicate that 30% to 75% of people infected with HIV use complementary or alternative therapies to manage their health (Gillett, Pawluch, & Cain, 2002). These therapies include massage, exercise, tai chi, chiropractic, and acupuncture. Other practices include reiki, reflexology, oxygen therapy, fever bush, aromatherapy, homeopathy, and herbal medicine. To the degree that complementary therapies help patients manage side effects, cope with the psychological stresses of HIV infection, and decrease feelings of hopelessness, they may contribute to improved adherence to antiretroviral regimens. On the other hand, alternative therapies such as herbal remedies may be associated with safety risks and potential interactions with components of HAART that can ultimately reduce adherence (Panel on Clinical Practices for Treatment of HIV Infection, 2004). It is important to obtain a thorough medication history including over-the-counter and herbal remedies from all HIV-positive patients. Patients often do not perceive these medications as drugs and may be unaware of potential drug interactions.

Improving Patient Adherence

To be successful, strategies to improve adherence cannot simply target the patient; rather, they must use a holistic approach that targets the patient, the provider, and the regimen. The foundation for adherence consists of patient education, frequent reinforcement of teaching, and ongoing assessment of adherence-related issues. Table 2 summarizes strategies for improved adherence (Williams, 1999; Williams, 2001).

Table 2
Table 2:
Adherence Intervention Strategies

Patient Strategies

It is critical to assess and address patient issues before starting HAART. Patient issues to address include health beliefs and cultural values or practices that can impact adherence, personal support and concerns (e.g., inner strengths, social support, and confidentiality concerns) and priorities such as housing and food. Moreover, individual stage of readiness should be assessed. A paradigm such as the transtheoretical model of health behavior change can be applied to HIV prevention and behavioral change (Prochaska, Redding, Harlow, Rossi, & Velicer, 1994). It can be used to assess patient stage of behavior change or readiness and to develop appropriate interventions (Parsons, Huszti, Crudder, Rich, & Mendoza, 2000).

Studies of other chronic conditions such as hypertension, diabetes, and asthma have shown that adherence falls from approximately 50% when patients understand the dynamics and consequences of their disease to 30% when they have no understanding of their illness (Chesney, 2003). Consequences of nonadherence in patients with diabetes and hypertension, however, are usually reversed when adherence improves. Patients infected with HIV face more problematic consequences of nonadherence (e.g., treatment failure, drug resistance, disease progression, and death). Education should focus on the manner in which resistance develops and how nonadherence results in resistance [Chesney, 2003; Loughlin & Jensen, 2000]). Without this basic knowledge, many of the restrictions and demands of HIV therapy can seem either meaningless or counterintuitive. For example, patients who do not realize the role of suboptimal dosing in eliciting resistance are likely to think that “something is better than nothing” in terms of taking their medication.

The need to take medications at approximately the same time of day and at equal time intervals may also be difficult for patients to grasp without an understanding of the duration of drug action. It should be explained that taking doses of drugs at different times on different days may result in periods during which drug levels are inadequate, particularly with those medications having a short duration of action. Thus, for many drugs, long intervals between doses may result in decreased efficacy. Conversely, taking doses too close together can cause transient adverse effects (Claxton et al., 2001).

A variety of strategies can be used to help patients remember to take their drugs at the correct time. For example, providers can advise them to cue their medications to regularly scheduled activities in their lives such as watching a particular TV program or walking the dog (Graney et al., 2003). Patients can also be a source of creative solutions to some of the problems in managing complex regimens; therefore, it is important to ask them how they deal with these difficulties. Patient-generated strategies have special value for other patients because they have proven to work for people like themselves (Graney et al., 2003).

Provider Strategies

In contrast to physicians who tend to focus on disease, nurses have traditionally attended to the whole patient. Therefore, they are uniquely qualified to identify psychosocial factors such as lack of social support, denial of illness, and health beliefs that affect adherence and help patients deal with the practical problems involved in incorporating difficult regimens into their lives. The nurse can also play a pivotal role as an intermediary between patient and physician. For example, although it is important for physicians to know what alternative or complementary treatments patients are receiving, nurses may be in a better position to discuss these treatments with patients because of their long-standing interest and experience in holistic patient care (Gillett et al., 2002; Haile et al., 2002).

Although providers are generally poor at estimating patient adherence, the ability to assess adherence can be greatly improved by carefully structured questioning. In addressing adherence with patients, it is important to ask questions that are concrete, open-ended, specific, and nonjudgmental, giving permission for lapses. The nurse should identify specific problems the patient experiences in being adherent and explore all possible side effects. It is also important to discuss the impact of treatment on the patient's quality of life and develop workable solutions or remedies with the patient (Williams, 1999). Adherence measures such as medication diaries and pharmacy reports can provide additional information to supplement and improve the accuracy of patient self-reports (Williams, 1999). Other adherence measures include pill counts, which require the active involvement of the patient, and the use of medication event-monitoring system caps. The latter is likely the most accurate measure of patient adherence but is also subject to technical difficulties (e.g., strict directions, measurements of bottle opening but not drug ingestion, precludes drug repackaging for convenient transport) that may adversely affect accuracy (Williams, 1999).

Nurses can also positively influence adherence through patient management and support as well as provide expertise during treatment initiation (Williams, 1999). Patient education is a critical component of the guidance and support a nurse can provide. Frequent follow-up through telephone contact or brief clinic encounters in the first few weeks on a new HAART regimen will help identify problems early. Home visits have been correlated with significant improvement in adherence that surpasses the traditional effects of education alone.

Regardless of the approach used to improve adherence, the patient-nurse relationship is the key to its success (Williams, 1999). Adherence should be continually reassessed and reinforced. Although nurses are in an excellent position to facilitate strategies for successful treatment, to make the most of this opportunity they must be conscious of the patients' need to be full collaborators in their therapy and to have their feelings and their desire for validation and autonomy respected (Haile et al., 2002).

Regimen Strategies

Treatment-related side effects and difficulty in incorporating treatment regimens into daily activities are important reasons for nonadherence to HIV therapy. Thus, any attempt to improve adherence should address these problems. Within the often limited alternatives that are possible for a given patient (Williams, 2001), selecting a HAART regimen that fits into the patient's lifestyle is best done collaboratively with the provider and the patient based on pill burden, dosing schedule, and potential side effects (Chesney, 2003). The introduction of antiretroviral agents with extended half-lives, combination tablets, and once-daily dosing has simplified HAART, making it less intrusive to daily activity. Less frequent dosing is also more conducive for using directly observed therapy as a means to promote adherence in settings such as drug clinics and correctional facilities (Williams, 1999). Antiretroviral agents that have been approved for once-daily dosing include the single PI atazanavir, PI combinations (ritonavir-boosted saquinivir, lopinavir-ritonavir and ritonavir-boosted fosamprenavir for treatment-naive patients), the nonnucleoside reverse transcriptase inhibitor efavirenz, and several nucleoside/nucleotide reverse transcriptase inhibitors (didanosine, tenofovir, lamivudine, and emtricitabine). Epzicom (GlaxoSmithKline, Philadelphia, PA) is a combination of abacavir and lamivudine; Truvada (Gilead, Foster City, CA) is a combination of tenefovir and emtricitabine. Both are dosed one pill once daily. The majority of these once-daily agents also offer the added benefit of low pill burden (one or two pills per day).

Successful management of side effects is of primary importance in achieving adherence in all patients, but it is crucial for those who have few therapeutic alternatives. Preparing and educating patients in advance regarding expected toxicities increases their ability to deal with these effects and facilitates adherence (Chesney, 2003). Recognizing toxicities as soon as they occur and managing them early in treatment limits their impact on adherence and helps to maintain the patient's quality of life (Ickovics et al., 2002).

It is preferable, when feasible, to avoid drugs that elicit toxicities. For example, unlike other PIs, the use of atazanavir has not been associated with clinically relevant dyslipidemia. Therefore, incorporation of this drug in HAART regimens may avoid future health consequences of PI-related metabolic side effects (Cahn et al., 2002; Piliero et al., 2002). Tenofovir disoproxil fumarate (DF) has also been associated with better lipid profiles compared with other agents. In a 3-year randomized comparative study, tenofovir DF in combination with lamivudine and efavirenz was equally as effective as stavudine in combination with lamivudine and efavirenz; however, there was less investigator-reported lipodystrophy in the tenofovir DF–treated group (Gallant et al., 2004). Unfortunately, the task of choosing less toxic agents is not always straightforward. Although there were no differences in renal safety in the study comparing tenofovir DF and stavudine, tenofovir DF is associated with increased renal impairment, particularly in patients with a history of renal dysfunction (Prescribing information: Viread, 2003). Therefore, it is necessary to balance and negotiate once-daily regimen options with efficacy data, potential toxicities, and individual patient needs.

Summary

As a result of their unique skills and holistic perspective, nurses are increasingly becoming the key facilitators of successful HIV/AIDS treatment because they are in the best position to address the obstacles to full adherence. These barriers include factors related to the disease, the patient, the provider, and the treatment regimen; hence, any effort to improve patient adherence should focus on all these components. Patient education has increasingly become the responsibility of nurses. Effective educational programs must go beyond an explanation of how to take medications to include information about the dynamics of HIV infection, the consequences of nonadherence, the role of suboptimal dosing in the development of viral resistance, and the relationship between duration of drug action and the need for correct timing of medications. While new agents may help to simplify HAART and avoid serious toxicities thereby reducing the incidence of important causes of nonadherence, the important role nurses play in facilitating adherence should not be underestimated. Perhaps the greatest contribution nurses can make in facilitating adherence is to help patients avoid or manage side effects and incorporate complex regimens into their daily activities.

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Keywords:

HIV; adherence; HAART

©2006 Association of Nurses in AIDS Care