ADHERENCE TO ANTIRETROVIRAL THERAPY AMONG HIV-INFECTED PATIENTS WITH MENTAL HEALTH DISORDERS

I. INTRODUCTION RECOMMENDATION: Patients with mental health disorders should be considered candidates for HAART if they meet the medical eligibility criteria for HAART and demonstrate readiness to begin therapy. Clinicians should determine treatment readiness on a case-by-case basis, weighing such factors as whether the patient attends the majority of his/her appointments and whether he/she expresses an interest in receiving ARV therapy. Patients with mental health disorders should be considered candidates for HAART if they meet the medical eligibility criteria for HAART and demonstrate readiness to begin therapy. Whether a patient is ready to begin therapy needs to be determined on a case-by-case basis; however, factors such as whether the patient attends the majority of his/her appointments and expresses interest in receiving ARV treatment will help to determine whether the patient is ready. Achievement of the benefits of HAART requires careful adherence to regimens that may be complex and/or cause unpleasant side effects. Non-adherence to ARV therapy may result not only in reduced treatment efficacy but also in the selection of drug-resistant HIV strains and increased progression to AIDS and death.1,2 Because the exact level of adherence that is necessary to prevent the emergence of drug-resistant virus or to delay disease progression to AIDS and death is unknown, near-perfect adherence (>90% to 95%) remains the goal for all HIV-infected patients,3,4 including those with mental health disorders or a history of mental health disorders. Appropriate identification and treatment, or referral for treatment, of underlying mental health disorders will facilitate optimal adherence among this patient population. Depression, the most studied mental health disorder, has been shown to be predictive of poor adherence.5,6 However, an improvement of depressive symptoms should result in improved adherence.7 Key Point: The most effective means of promoting adherence in patients with mental health disorders is through adequate stabilization of their mental health and integration of mental health treatment into the comprehensive treatment plan.

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II. COORDINATION OF CARE RECOMMENDATIONS: Primary care clinicians should refer patients to licensed mental health providers when:

Initial mental health treatment by the primary care clinician is ineffective Complex mental status evaluations become necessary or a patients behavior

jeopardizes effective treatment The patient has co-occurring mental health and substance use disorders

Primary care clinicians and mental health care providers should collaborate to develop a step-by-step treatment plan. The treatment plan should delineate the frequency of follow-up visits with both providers as well as the frequency of team meetings to reevaluate effectiveness of the overall medical and mental health treatment. Primary care clinicians should initially consult with a psychiatrist when managing patients with mental health disorders who refuse mental health care. Throughout the patients care, the clinician should communicate with a psychiatrist or a licensed mental health professional who can provide consultation. Primary care clinicians should notify the mental health care provider when there is a change in medical or mental health treatment. The care for HIV-infected patients with mental health disorders should be a collaborative effort involving patients, primary care clinicians, and mental health providers. Extra attention and involvement of the care team may be required to ensure that these patients adhere to their ARV regimens. When patients are also taking psychotropic medications, adherence may be more difficult, which can make coordination of care even more critical. When necessary, case managers, substance use counselors, relatives, pharmacies, insurance companies, and domestic violence service providers should also be involved. Regular communication between primary care clinicians and the mental health provider(s) offers a chance to discuss techniques for approaching patients with mental health disorders. For patients who have established a therapeutic alliance with their mental health provider, a meeting involving the patient, the primary care clinician, and the mental health provider can help transfer the trust from the mental health provider to the primary care clinician. The same strategy can be used to transfer the trust from the primary care clinician to the mental health provider. This can help the patient feel that the care team takes a genuine interest in the his/her health. When patients with mental health disorders do not agree to mental health evaluation and treatment by a mental health professional, the primary clinician should establish a silent partnership with a licensed mental health professional who can help the primary clinician develop a treatment strategy for the patient. Because psychiatrists are physicians and are familiar with medical illnesses and their treatment, initial consultation with a psychiatrist would be ideal for the primary care clinician to establish the patients overall care. A licensed mental health professional may play the primary role as silent partner thereafter.

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A mental health patient who is enrolled in a methadone treatment program should be educated about drug-drug interactions because he/she may develop opiate withdrawal symptoms after initiating ARV treatment or other medications. The patient should also be asked to notify the medical staff at the drug treatment program that he/she is initiating ARV treatment. If symptoms occur, adjustment of methadone dose may need to be made with ongoing coordination between the primary care clinician and the patients methadone program. III. PREDICTORS OF AND BARRIERS TO ADHERENCE A. Predictors Predictors of adherence that have been consistently identified among persons with HIV infection with and without mental health disorders include the following:

Social stability and support Beliefs and knowledge about medications Confidence in their ability to adhere successfully to an ARV regimen A regimen that works (fits) with their daily activities8-10 A strong and trusting patient-provider relationship

Key Point: Patients with mental health disorders may have learned skills related to adherence to psychiatric medications that they can use to help them adhere to HIV treatment. B. Barriers Adherence to medication regimens, including ARV treatment, has been shown to be affected by mental health and psychosocial factors. Mental health factors that may affect adherence include:

Substance use disorders Affective disorders, such as bipolar disorder and depression Anxiety disorders, such as generalized anxiety disorder, panic disorder, post-traumatic

stress disorder (PTSD) Fluctuations in mental health status or impairments in cognitive function, which may

interfere with a patients ability to follow directions Personality characteristics, such as pessimism, apathy, and poor coping styles

Although mental health disorders and/or history of substance use disorders are not contraindications for initiation of treatment, these factors may make adherence more challenging. Active substance or alcohol use is one of the few relatively consistent predictors of poor adherence.11,12 Patients with severe affective disorders have also been found to have lower rates of adherence. However, it is noteworthy that, at least in one large study, patients with schizophrenia were found to be as adherent to ARV therapy as those without a serious mental health disorder.13

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Psychosocial factors that may affect adherence include: Lack of social support Homelessness Family instability Domestic violence Poor self-image and fears of stigma

Among homeless individuals, adherence may be compromised when they experience increased housing instability or stay in settings not conducive to adherence, such as moving from a residential hotel to a shelter, not having a secure place to keep medications, or not having a refrigerator for certain medications.14 IV. IDENTIFYING AND ADDRESSING POTENTIAL BARRIERS TO ADHERENCE BEFORE INITIATING HAART RECOMMENDATIONS: Clinicians should carefully assess each patient to evaluate his/her ability to adhere to HAART. Clinicians should identify and address potential barriers to adherence before initiating HAART. If clinicians elect to defer HAART while addressing potentially modifiable barriers to adherence, they should discuss this decision with the patient and document it in the medical record. Clinicians should discuss the following with patients before initiating HAART:

Clinician and patient treatment goals Patients concerns about treatment and ability to adhere Potential side effects of ARV therapy and potential interactions with psychotropic

and other medications, as well as how the side effects and interactions will be managed should they occur

Clinicians should use translator or sign language services when language barriers exist. Primary care clinicians should refer patients with mental health disorders to specialized adherence services when adherence barriers cannot be resolved, particularly if the patient has AIDS or is at risk for advanced progression of HIV. Determination of a patients ability to adhere and promotion of adherence are processes that begin before patients actually start taking medications. Identification and management of potential barriers to adherence before initiating HAART in HIV-infected patients with mental health disorders are critical (see Table 1). Clinicians may choose to defer HAART while addressing potentially modifiable barriers to adherence. In patients with advanced AIDS, it may be appropriate to initiate HAART, even if barriers to adherence are present. In these cases, referrals to specialized adherence programs should be made for intensified adherence support. Listings of local pharmacies, designated AIDS centers, and local HIV/AIDS social service organizations can be found in Appendix A.

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An initial step in the identification and management of barriers to adherence involves a discussion with the patient about his/her treatment goals. Discussions about treatment goals involve the patient in the decision of when to initiate therapy. The clinician should not assume that the patients goals are the same as the clinicians goals. For example, the clinicians main goal may be viral load suppression, whereas the patients main goal may be to look healthier. Discussion points may include the following:

If the clinician and patient have different goals, how can they bridge the difference? How realistic are the patients goals? Which symptoms might impede him/her in achieving his/her goals?

After discussing treatment goals, the clinician should give the patient the opportunity to discuss his/her concerns about treatment readiness: How hopeful is the patient about adherence to both HIV and psychotropic medications? Some patients may fear the consequences of initiating HAART. For example, the patient may be afraid of:

The stigma associated with receiving HAART Losing government benefits if his/her medical status improves Giving up psychological or material benefits associated with the sick role Returning to an anxious state of uncertainty about the length of time that the medications

will be effective By expressing interest in the patients concerns and goals, the clinician may both strengthen the patient-provider relationship as well as provide means for supporting HIV treatment adherence. For example, a patient with a history of trauma might be too anxious to put a potentially toxic medication into his/her body. The patients commitment to HIV care may be strengthened by the clinician showing an active interest in learning about the patients anxiety and related social concerns:

Who in the patients life is aware and supportive of his/her mental health problems? What kind of experience has he/she had with mental health professionals and psychiatric

medications? Does the patient have health beliefs or cultural beliefs about western medicine that are

causing additional anxiety about taking medication? When assessing readiness for treatment in patients with mental health disorders, the factors in Table 1 should be considered as potential barriers.

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TABLE 1

ASSESSMENT AND APPROACHES TO POTENTIAL BARRIERS TO ADHERENCE Barriers Assessment Possible Approaches

Stage of acceptance Is the patient in denial? Educational approaches; motivational interviewing; medication education support group; consider referral for counseling

Mental health Is there an untreated mental health disorder?

Treat the underlying mental health symptoms; refer for treatment; silent partner with mental health provider

Cognitive function Does the patient understand instructions?

See Cognitive Disorders and HIV/AIDS; see Table 2; see below (Section VI, D. Cognitive-Behavioral Strategies)

Language barriers Do the clinician and patient speak the same native language? Is the patient deaf or does the patient have a hearing impairment?

Translator or sign language interpreter; someone who does not know the patient may be preferable

Substance use Is there active substance use or inadequate substance use treatment?

See Substance Use Guidelines

Presence and severity of particular symptoms

Are any of the following symptoms present? Helplessness; hopelessness; negativity; lack of motivation; apathy; low energy and easy fatigue; stigma and shame about HIV or mental health disorders; low self-esteem; depression; and inadequate coping styles, especially under stress.15,16

Treatment adherence support program; screen for common mental health disorders; if symptoms are due to a personality disorder, see Management of Patients with Personality Disorders; consider full mental health evaluation

Support network and social stability

What is the degree of support from family and friends? Is there lack of social stability (e.g., housing problems, legal issues)? Are children or other dependents in the home? Is there domestic violence?

With patients consent, consider involving family, friends, HIV social service organization, case management services

History of abuse or violence Does the patient have PTSD symptoms?

See Trauma and Post-Traumatic Stress Disorder in Patients With HIV/AIDS

Medication concerns Has the patient had poor past experiences handling side effects? Would the regimen fit with the patients daily routine? Is there a risk of drug-drug interactions?

Consider regimen that accommodates lifestyle; avoid regimens with possible side effects that would likely lead to poor adherence

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The more disorganized and chaotic a patients life is, the more important improved treatment-setting characteristics and supportive services become:

Optimizing Treatment-Setting Characteristics Offer the following: - Assurances of confidentiality - Incentives to keep appointments, such as food and travel vouchers - More frequent follow-up monitoring - A comfortable, private, and welcoming clinic setting - Improved waiting time in the clinic, particularly for patients with personality

disorders, who often have poor coping skills and a very low tolerance for frustration. Clinicians may consider arranging these patients appointments at the beginning of the day or arranging a special slot because patients who feel shamed and stigmatized may feel too uncomfortable to wait in an area with other patients. Patients experiencing uncontrollable muscle movement or who have difficulty sitting still for any reason may be disruptive to the waiting area.

Referrals for Services

Refer patients as needed: - To adherence support groups and adherence research projects - For food and nutritional supplements - To case-management services for assistance in obtaining financial support,

housing, and childcare and help with managing the cost or coverage of drugs, medical care, and transportation for traveling to appointments

- To various services, such as outpatient mental health clinics, HIV adult day programs, psychiatric day programs, mental health residential programs, nutritional programs, stress-management services, and professionally or peer-led support groups

Designated AIDS centers, HIV/AIDS social service organizations, and select pharmacies offer educational programs and support groups designed to help patients with medication adherence. Some programs may target particular issues related to adherence. For example, some target their services to patients who are starting their first ARV regimen. Listings of local pharmacies, designated AIDS centers, and local HIV/AIDS social service organizations can be found in Appendix A and at http://www.nyhiv.org/resources_programs.html. V. INITIATING, MEASURING, AND MONITORING ADHERENCE TO ARV THERAPY RECOMMENDATIONS: Clinicians should assess adherence at every routine monitoring visit by verifying that patients are taking the correct medications, correct number of pills per dose, and correct number of doses per day. Clinicians should use finite time intervals when inquiring about and quantifying the patients self-report. Clinicians should calculate an average response rate based on information obtained at multiple visits to determine a more accurate estimate of adherence.

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Clinicians should reassess potential barriers to adherence at least every 3 to 4 months and whenever adherence problems are identified. When clinicians find it necessary to speak with the patients friends or family to assess adherence, permission should be obtained from the patient and the patient should be involved in these discussions. Measurement of adherence is challenging in both clinical and research settings and usually relies on any one or a combination of the following methods:

Self-report Pill counts Pharmacy records Electronic pill bottle monitors Therapeutic drug monitoring Computer-assisted self-interview (CASI) assessment

The advantages and disadvantages of each method are discussed in Appendix B. When adherence is assessed, finite time intervals should be used. For example, the clinician should ask about the number of doses taken and missed in the past day or past week. Despite its tendency to overestimate adherence, self-report remains the most practical measure in most clinical settings and is most likely to facilitate discussion between patients and providers about the reasons for non-adherence. Self-report is most valid when patients are asked about the number of missed doses within a short time frame (1-7 days), but some studies have found that asking about adherence within the past month is also valid.17,18 In addition to the usual means of assessing adherence, primary care clinicians may need to involve input from licensed mental health providers, case managers, friends, and/or family members of patients with active mental health disorders. When clinicians find it necessary to speak with the patients friends or family to assess adherence, permission should be obtained from the patient and the patient should be involved in these discussions. As ongoing adherence to treatment is monitored, the factors described in Table 1 should be considered. VI. STRATEGIES TO IMPROVE ADHERENCE A. Patient-Provider Interaction Strategies RECOMMENDATIONS: Clinicians should encourage patients to state in their own words what they understand about treatment instructions and to ask questions when additional information is needed. Clinicians should encourage patients to be honest by responding in a nonjudgmental, supportive manner when patients report non-adherence.

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Factors such as the clinicians language, eye contact, ability to listen, communication skills, and consultation style can foster or hinder collaboration with the patient. Factors that facilitate the relationship include the provision of understandable information, openness to questions, sensitivity and respect for the patient, interest and trust in the patient, and ongoing availability. Key Point: A strong patient-provider relationship, including trust and engagement with the provider, has been associated with improved ARV adherence.19

Table 2 lists communication strategies for the enhancement of adherence in patients with mental health and/or substance use disorders. Interventions work best when they are practical, initiated promptly, and individualized to the patients characteristics and needs.

TABLE 2 COMMUNICATION STRATEGIES FOR CLINICIANS TREATING PATIENTS WITH MENTAL

HEALTH AND/OR SUBSTANCE USE DISORDERS Proceed slowly; repeat key points; have patients repeat back instructions in their own

words Teach science in simple terms Allow honest reporting of non-adherence Use translator or sign language services when language barriers exist Use pictures and/or written material

Involvement of the patient as a partner in his/her care will help foster trust and build a strong patient-provider relationship. Strategies to involve patients as partners in their care include the following:

Asking the patient to repeat medication information regularly Encouraging the patient to ask questions and providing clarifying information Inviting the patients feedback and opinions and role-playing problem scenarios Involving the patients family or friends, mental health provider, and case managers in

treatment recommendations and supervision Having the patient and provider agree on an accepted regimen and encouraging the use of

the simplest effective regimen (e.g., number of doses, number of times) Having the patient develop a calendar or schedule for taking medications Performing a practice run without active medication (e.g., using candy, vitamins)

When a patient reports non-adherence, the clinician should respond in a way that enhances an open and honest partnership. Clinicians can be supportive by acknowledging that treatment for multiple disorders is challenging because of the increased pill burden and added responsibility and stress of adhering to more than one regimen. Being actively supportive by welcoming the patients honesty will mitigate any shame that the patient may feel about his/her poor adherence.

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The clinician might say, Everyone has difficulty taking medications. The fact that you sometimes remember to take your pills is great. It will help us understand the best way for you take your pills regularly. So, lets review when you do remember and when you dont. B. Health Educational Strategies RECOMMENDATION: Clinicians should provide adherence information in an organized manner, both orally and in written form, with easy-to-understand brief statements. Health educational strategies are most effective when the patient receives information, both orally and in written form, that is well organized and easy to understand. Clinicians should convey education points through the use of brief statements. Important educational topics for clinicians and patients to discuss are given in Table 3.

TABLE 3 HEALTH EDUCATION POINTS FOR ENHANCING ADHERENCE

The treatment regimen and treatment options Drug side effects, with special attention to psychiatric side effectshow to address or

avoid Drug-drug interactionshow to determine whether interactions are occurring and what

to do about them; which drugs do not have any known risks for or lack of likelihood for drug-drug interactions with prescribed and alternative medications, methadone, recreational drugs, and/or alcohol

The importance of treating comorbid disorders, such as mental health and substance use disorders

The possible impact of HIV on mental health symptoms

Educational tools can be helpful; yet these should complement and enhance the direct communication and not replace it. These tools need to be tailored to the patient (using lay language or native language). (See Adherence - Best Practices booklet.) C. Motivational Strategies Motivational strategies can help to address attitudinal barriers and may include providing psychosocial support and involving family members, partners, and social and community organizations. A therapeutic treatment style that may be used when exploring issues of ambivalence and conflict regarding adherence is motivational interviewing. Through use of motivational interviewing, the clinician attempts to stimulate change by identifying discrepancies in the patients current behavior and the patients goals of healthier behaviors. When the patient begins

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to understand how the consequences of current behavior conflict with personal values, the clinician reflects the discordance back to the patient, until the patient realizes that change is necessary and makes the decision to commit to change. This approach encourages patients to describe their behaviors and develop their own solutions. For patients who have difficulty tolerating direct communication or who may not be able to identify their own needs, use of motivational interviewing may not be suitable. Direct persuasion and aggressive confrontation are not part of motivational interviewing. With this approach, clinicians do not give advice or directives. 1. Principles of Motivational Interviewing Clinicians should understand the underlying principles of motivational interviewing before using it. The four key components of motivational interviewing are shown in Table 4.

TABLE 4 KEY COMPONENTS OF MOTIVATIONAL INTERVIEWING

Component Involves Expressing empathy

Understanding and being aware of and sensitive to the feelings, thoughts, and experiences of another. Accomplished through reflective listening.

Supporting self-efficacy

Supporting the patient with the sense that an individual can identify and meet ones needs and goals.

Avoiding argumentation and rolling with resistance

Listening to the patients resistance to change. Working collaboratively with the patient to develop his/her input regarding the treatment plan.

Discovering discrepancies

Helping patients identify discrepancies between their current behavior and desired future behavior.

Expressing Empathy: To gain a better understanding of the patients perspective, the clinician actively listens without being judgmental. Through this reflective listening, the clinician may find that the patient is not ready or willing to stop engaging in a particular behavior or to adopt a new behavior. In this case, the initial focus is on building therapeutic rapport and supporting the patient, instead of verbally suggesting change. Supporting self-efficacy: Self-efficacy refers to a persons belief in his/her ability to successfully carry out a specific task. The clinician should support the patients belief in his/her ability to change by giving the patient examples of positive change and emphasizing the importance of taking responsibility. When the patient feels strong support from the clinician, it enhances his/her sense of self-efficacy.

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Avoiding argumentation and rolling with resistance: Motivational interviewing differs from other approaches to behavior change in that it does not label patients (e.g., non-compliant or difficult). When faced with a patients resistance, it is important for the clinician to allow the resistance to be expressed. Through this process, the clinician reflects the patients questions and concerns back to the patient, so that the patient may further examine the possible alternatives to this resistance. The patient then becomes the source of the positive actions that could be taken, does not feel defeated in sharing his/her concerns, and is able to take the risk to express feelings. Discovering discrepancies: Once patient-provider rapport has been established, the goal is to discover and amplify discrepancies between present and past behavior and future goals. This is achieved through examination of the consequences of continuing an unhealthy behavior and often involves discussing the advantages of adopting a new behavior. The patient will then be able to present the argument for change and begin to realize the need for change. 2. Motivational Interviewing Approach The acronym OARS outlines the basic approach to interactions in motivational interviewing: Open-ended questions invite patients to provide more information than yes or no and will encourage them to explore their own motivators for change. This strategy lets the patient know that the clinician is interested in his/her situation, while allowing the clinician to obtain needed information and insight into the patients issues. Affirmations provide opportunities for clinicians to recognize the patients strengths. Reflective listening helps the clinician identify areas of ambivalence. Reflective listening is often challenging because the clinician may need to form assumptions about the meaning of the patients statements in order to articulate them back to the patient. It is particularly important to reflect back any statements that indicate that the patient is motivated to change. Simple reflections acknowledge the patients statements about disagreements, feelings, or perceptions. Double-sided reflections acknowledge both what the patient has said and the ambivalence. Amplified reflections reveal the patients ambivalence in a slightly exaggerated form. Summaries will emphasize the main points of the discussion and should capture both sides of the patients ambivalence. The summary can also be used to shift focus or direction when the patient is expressing impassible resistance. After the clinician summarizes, he/she should invite the patient to make any corrections. More resources on motivational interviewing are available at http://www.motivationalinterview.org.

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D. Cognitive-Behavioral Strategies Cognitive-behavioral strategies can be used when mild memory difficulties are present or when the individual feels overwhelmed by the pill-taking challenge. Practical strategies include the following:

Simplifying regimens: decrease dosing frequency, decrease number of pills Personalizing drug schedules: tailor treatment to lifestyle, link medications to daily

activities Using reminders: written instructions or illustrations, pill boxes, timers, diaries, phone

calls from family or friends Using available pharmacy services: pharmacies may call patients to remind them about

need for refills, deliver medications, provide professional regimen reviews If memory deficits are pronounced, after evaluation by a neurologist, the assistance of relatives, home health aides, or visiting nurses should be sought. Before initiating treatment or when switching regimens, a practice run without active medication can help a client feel confident about his/her ability to adhere to ARV therapy. For more information regarding cognitive impairment among HIV-infected patients, see Cognitive Disorders and HIV/AIDS: HIV-Associated Dementia and Delirium. E. Directly Observed Therapy Some medical programs and HIV/AIDS social service organizations have programs that provide ARV directly observed therapy (DOT) for outpatients (see Appendix B). Although shown to be effective in several non-randomized trials,20,21 published data are limited that compare the efficacy of DOT with other modalities for successful treatment of HIV disease. DOT and modified DOT (MDOT) may facilitate adherence through direct supervision of pill-taking. These programs may also include psychoeducational and social service components, as well as behavioral reinforcements. DOT and MDOT may be the only effective means of ensuring treatment adherence in some patients with severe and persistent mental health illness, those with dual mental health and substance use disorders, and those who are living in unstable and disorganized social conditions. REFERENCES 1. Bangsberg DR, Hecht FM, Charlebois ED, et al. Adherence to protease inhibitors, HIV-1 viral load, and development of drug resistance in an indigent population. AIDS 2000;14:357-366. 2. Montaner JSG, Reiss P, Cooper D, et al. A randomized, double-blind trial comparing combinations of nevirapine, didanosine, and zidovudine for HIV-infected patients. JAMA 1998;279:930-937. 3. Bangsberg DR, Perry S, Charlebois ED, et al. Non-adherence to highly active antiretroviral therapy predicts progressions to AIDS. AIDS 2001;15:1181-1183. 4. Lucas GM, Chaisson RE, Moore RD. Highly active antiretroviral therapy in a large urban clinic: Risk factors for virologic failure and adverse drug reactions. Ann Intern Med 1999;131:81-87.

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5. Gordillo V, del Amo J, Soriano V, et al. Sociodemographic and psychological variables influencing adherence to antiretroviral therapy. AIDS 1999;13:1763-1769. 6. Avants SK, Margolin A, Warburton LA, et al. Predictors of nonadherence to HIV-related medication regimens during methadone stabilization. Am J Addict 2001;10:69-78. 7. Starace F, Ammassari A, Trotta MP, et al. Depression is a risk factor for suboptimal adherence to highly active antiretroviral therapy. J Acquir Immune Defic Syndr 2002;3(Suppl 3):S136-S139. 8. Chesney MA, Ickovics JR, Chambers DB, et al. Self-reported adherence to antiretroviral medications among participants in HIV clinical trials: The AACTG adherence instruments. AIDS Care 2000;12:255-266. 9. Safren SA, Otto MW, Worth JL, et al. Two strategies to increase adherence to HIV antiretroviral medication: Life-steps and medication monitoring. Behav Res Ther 2001;39:1151-1162. 10. Kalichman SC, Ramachandran B, Catz S. Adherence to combination antiretroviral therapies in HIV patients of low health literacy. J Gen Intern Med 1999;14:267-273. 11. Haubrich RH, Little SJ, Currier JS, et al. The value of patient-reported adherence to antiretroviral therapy in predicting virologic and immunologic response. AIDS 1999;13:1099-1107. 12. Arnsten JH, Demas PA , Grant RW, et al. Impact of active drug use on antiretroviral therapy adherence and viral suppression in HIV-infected drug users. J Gen Intern Med 2002;17:377-381. 13. Walkup JT, Sambamoorthi U, Crystal S. Use of newer antiretroviral treatments among HIV-infected Medicaid beneficiaries with serious mental illness. J Clin Psychiatry 2004;65:1180-1189. 14. Community Health Advisory and Information Network. Report 2004-1: Service Gaps and Utilization in the Continuum of Care in NYC. New York: HIV Health and Human Services Planning Council. Available at: http://www.nyhiv.org/pdfs/chain/CHAIN%20Service%20Gaps%20Report%202004_12.pdf. 15. Chesney MA. New antiretroviral therapies: Adherence challenges and strategies. Evolving HIV Treatments: Advances and the Challenge to Adherence, 37th ICAAC Symposium, Toronto, Canada, September 1997. 16. Singh N, Squier C, Sivek C, Wagener M, et al. Determinants of compliance with antiretroviral therapy in patients with human immunodeficiency virus: prospective assessment with implications for enhancing compliance. AIDS Care 1996:8:261-269. 17. Walsh JC. Responses to a 1 month self-report on adherence to antiretroviral therapy are consistent with electronic data and virological treatment outcome. AIDS 2002;16:269-277. 18. Giordano TP, Guzman D, Clark R, et al. Measuring adherence to antiretroviral therapy in a diverse population using a visual analogue scale. HIV Clin Trials 2004;5:74-79. 19. Bakken S, Holzemer WL, Brown MA, et al. Relationships between perception of engagement with health care provider and demographic characteristics, health status, and adherence to therapeutic regimen in persons with HIV/AIDS. AIDS Patient Care STDs 2000;14:189-197. 20. Stenzel MS, McKenzie M, Adelson-Mitty J, et al. Enhancing adherence to HAART: A pilot program of modified directly observed therapy. AIDS Reader 2001;11:317-328. 21. Babudieri S, Aceti A, DOffizi GP, et al. Directly observed therapy to treat HIV infection in prisoners. JAMA 2000;284:179-180. FURTHER READING Osterberg L, Blaschke T. Adherence to medication. N Engl J Med 2005;353:487-497.

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APPENDIX A NEW YORK STATE ADHERENCE SERVICES CONTACT LIST

AIDS Community Resources Casey Cleary-Hammerstadt Deputy Executive Director 627 West Genesse St. Syracuse, NY 13204 (315) 475-2430 cch@aidscommunityresources.com Albany Medical College George Clifford, Ph.D. AIDS Program Administrator 47 New Scotland Av M Code 158 Albany, NY 12208 (518) 262-4432 Cliffog@mail.amc.edu Albert Einstein College of Medicine Dr. Daniel Kaswan Director, HIV Medical Services 1300 Morris Park Ave Bronx, New York 10461 (718) 665-7000 Bellevue Hospital Center Lucy Grugett Assistant Director, Grants Management 462 First Avenue, 12 E 12 New York, NY 10016 (212) 562-5201 Lucy.Grugett@bellevue.nychhc.org Beth Israel Medical Center Dr. Laurie Greenberg-Cardillo Manager, Mental Health and Treatment Adherence First Avenue at 16th Street New York, New York 10003 (212) 420-2617 lgreenb@bethisraelny.org

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Columbia University School of Public Health Emilyn Nishi, Project Director 722 West 168th Street, Rm 1111 New York, NY 10032-2603 (212)305-4104 EN2008@Columbia.edu Community Health Network Danita Djelosk Treatment Adherence Program Coordinator 87 North Clinton Ave., 4th Floor Rochester, NY 14604 (585) 244-9000, ext. 247 ddjeloski@achcrochester.org Erie County Medical Center Kathleen Walsh MSW, CSW AIDS Program Administrator 462 Grider St Buffalo, NY 14215 (716) 898-4481 kwalsh@ecmc.edu Harlem Hospital Center Sharon Mannheimer, MD Program Director Harlem Adherence to Treatment Support in Primary Care 506 Lenox Avenue, Room 3101A New York, NY 10037 (212) 939-2948 Sbm20@columbia.edu Kings County Hospital Center John Krevitt, MPH Associate Director 451 Clarkson Avenue Brooklyn, NY 11203 (718) 245-2821 Krevittj@nychhc.org Montefiore Medical Center Jorge Rodriguez Administrative Director HIV/AIDS Services 111 East 210th Street Bronx, NY 10467-2490 (718) 920-2199 Jorrodri@montefiore.org

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Nassau University Medical Center Getachew Feleke Chief, Infectious Diseases 2201 Hempstead Turnpike Mailbox 73 East Meadow, NY 11554 (516) 572-6506 gfeleke@ncmc.edu New York Presbyterian Medical Center Andrew Torres Coordinator, Education and Outreach 180 Fort Washington Avenue, #624 New York, NY 10032-3710 (212) 305-8925 Ant9009@nyp.org North Shore Long Island Jewish Medical Center -Schneider Childrens Hospital Dr. Susan Schuval Section Head Pediatric Immunology

865 Northern Blvd. Suite 101 Great Neck, NY 11021 (516) 622-5070 or 5064 Schuval@lij.edu SUNY Downstate Medical Center Alexa Kazim Administrative Director STAR Health Center HIV Service Box 1240, 450 Clarkson Avenue Brooklyn, NY 11203 (718) 270-3818 Alexa.kazim@downstate.edu Village Center of Care Laurie Newman, MPH Director of Research 154 Christopher Street Suite 3A New York, NY 10014 (212) 337-5854 laurien@vcny.org

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Westchester Medical Center Richard Birchard, MS Coordinator, HIV Clinical Education and Adherence AIDS Care Center BHC-S022 Valhalla, NY 10595-1689 (914) 493-1362 birchardR@wcmc.com

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APPENDIX B

ADVANTAGES AND DISADVANTAGES OF ADHERENCE MEASURES

Method Advantages Disadvantages Directly Observed Therapy 100% adherence, in theory

Ideal method for institutional

settings (prisons, nursing homes, residential treatment programs, etc.)

Labor intensive Not practical for complex regimens

with multiple doses and/or dietary restrictions

May compromise confidentiality

Electronic monitoring Best correlation with virologic outcomes

Allows more detailed view of

non-adherence patterns Most accurate measure

Expensive and generally reserved for clinical trials

Precludes use of pillbox Fails if multiple medications are

kept in a single bottle or if multiple doses are taken out at one time

Requires carrying the container Subject to pocket doses (removing

more than one dose at a time) Does not guarantee that the patient

took the medication

Hematologic monitoring using either complete blood counts or expanded chemistry panels

Confirms patient reporting Only effective for certain drugs: Zidovudine, Stavudine (increased MCV); Indinavir (increased bilirubin)

Not always reliable

Modified Directly Observed Therapy (observation of most but not all medication doses)

100% adherence, in theory Ideal method for ambulatory

settings

Labor intensive Concern for development of

resistance if plan not followed

Pharmacy refill monitoring Easy, minimal time commitment Timely refilling of prescriptions

correlates well with adherence Most successful when limited to

patient using one pharmacist Is a useful adjunct to self-report Effective in understanding

adherence behavior in large populations

Patients may use more than one pharmacy

Does not equate with medication-

taking

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Pill counts Useful adjunct to self-report Unannounced pill counts may be

more accurate Direct costs minimal

Tends to overestimate adherence because of pill dumping before visit

Casts provider in the role of

medication monitor and not ally or advocate

Indirect costs a concern due to time

constraints Does not prove that patient actually

took medication

Provider estimation Most poorly correlated with actual adherence

Self-report Easily obtained using patient

interview or questionnaire (report of non-adherence is more reliable than report of adherence)

Inexpensive

Overestimates adherence Correlation is dependent on

patients relationship with staff Individuals may give providers what

they perceive as socially desirable, right responses

Therapeutic drug monitoring Low drug levels confirm non-

adherence, but therapeutic drug levels do not confirm adherence

Pharmacokinetic levels for most drugs have not been well established

Only confirms the pre-measurement

adherence, long-term adherence still unknown

Viral load Can correlate with adherence

Although poor adherence is

associated with virologic failure, not all individuals with virologic failure will be poor adherers

Does not necessarily indicate non-adherence

May overestimate adherence Virologic failure can be indicative

of drug resistance

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Albert Einstein College of MedicineBellevue Hospital CenterColumbia University School of Public HealthNassau University Medical CenterNew York Presbyterian Medical CenterNorth Shore Long Island Jewish Medical Center -Schneider Childrens HospitalVillage Center of CareWestchester Medical Center