1. Importance of Adherence for ART Success HIV Care and ART: A Course for Pharmacists

2. 2 Introductory Case: Abebech  Abebech is a HIV+ 30 year-old female who presents to the pharmacy with refill prescriptions for the following: Lopinavir/ritonavir 3 caps bid Zidovudine 300 mg bid Lamivudine 150 mg bid

3. 3 Introductory Case: Abebech (cont.)  You are a thorough pharmacist and you ask her the following questions before filling her prescriptions: How are you tolerating your medication? Are you taking any new medications? Are you able to remember to take all of your doses? How are you taking your doses?

4. 4 Introductory Case: Abebech (cont.)  She responds with the following information: She has been taking her medications for 1 month. She gets occasional diarrhea, which she controls by increasing her intake of starchy foods She is not taking any new medications She is proud to tell you that she has made her medication last for 2 months rather than one month, because she only takes 1 rather than 2 doses a day to make her pills last longer. She remembers to take her dose every morning, except when she is late for work

5. 5 Introductory Case: Abebech (cont.)  Which of the following statements regarding counseling Abebech on adherence is true? 1.You have to miss a lot of doses before ART becomes ineffective 2.ART must be taken as prescribed to avoid the development of resistance and possible treatment failure 3.If any doses of ART are missed, a change in ART regimen will be necessary 4.Taking less than the prescribed dose is an effective way to make ART last longer without going to the pharmacy

6. 6 Unit Learning Objectives  Identify challenges and barriers for adherence to ART  Review the consequences of ART non-adherence on patient outcomes  Explain strategies to promote adherence  Identify methods of adherence assessment and/or monitoring

7. 7 What is Adherence?  Adherence is a client’s behavior coinciding with the prescribed health care regimen  Regimen is agreed upon through a shared decision making process between the client and the health care provider

8. 8 Adherence versus Compliance  The term compliance is defined as acting in accordance to a command  In health care: Compliance is often perceived as obeying a provider’s instructions Adherence is perceived as a patient agreeing to make behavioral changes that improve his or her health

9. 9 Why is Adherence to ART Important?  HAART reduces morbidity, mortality, and overall health care costs for HIV+ persons, if properly taken Achieves viral suppression Avoids development of viral resistance Prevents development of opportunistic infections and treatment failure  ARV should not be prescribed in the absence of adherence assessment and support

10. 10 Consequences of Poor Adherence  Incomplete viral suppression  Continued destruction of the immune system  Disease progression  Emergence of resistant viral strains  Limited future treatment options  Higher costs to the individual and ARV program

11. 11 How Much Adherence is Required for Success?  To achieve maximum and durable viral suppression (to undetectable levels) adherence must be >95% Less than 3 doses missed per month  Failure rates increase sharply as adherence decreases

12. 12 Introductory Case: Abebech (cont.) 1.You have to miss a lot of doses before ART becomes ineffective FALSE Taking less than 95% of prescribed doses leads to reduced virologic control Counsel the patient on the need for adherence Recommend that she get a follow-up CD4 or TLC count every 3 months to detect drug failure

13. 13 PI adherence, % (electronic bottle caps) Virologic Control Falls Sharply with Diminished Adherence Source: Paterson, D. L. et. al. Ann Intern Med 2000;133:21-30 (number of pills taken / number of pills prescribed)

14. 14 Adherence and Antiretroviral Drug Resistance  Sub-optimal adherence predisposes to resistance: Association between poor adherence and antiretroviral resistance is well-documented 1,2 Sub-optimal adherence Sub-therapeutic drug levels Incomplete viral suppression Generation of resistant HIV strains by selection for mutant viruses 1. Vanhove G, et al. JAMA. 1996;276:1955-1956. 2. Montaner JS, et al. JAMA. 1998;279:930-937.

15. 15 Missed Doses & Development of Drug Resistance  When blood levels fall below the level needed to prevent resistant virus from growing, the resistant virus overgrows the sensitive virus

16. 16 Introductory Case: Abebech (cont.) 2.ART must be taken as prescribed to avoid the development of resistance and possible treatment failure TRUE

17. 17 How Common is Non-Adherence?  Estimated rates of non-adherence to medications range from 10% to nearly 100%, with an average incidence of about 50%  Non-adherence to ART, likewise, is common in all groups of individuals on treatment >10% patients report missing one or more doses on any given day 1 >33% report missing doses in the past 2 to 4 weeks 1  Partly due to non-adherence, ART fails in approximately half of patients for whom it is prescribed 2 1. Ickovics, J.R. et al., JAIDS, 2002.. 2. Valdez L, et al., Arch Intern Med, 1999.

18. 18 Adherence to ARVs in Resource-Limited Settings  Uganda: 88%  Cote d’Ivoire: 75%  Haiti: 88%  Senegal: 78%, 42%, 88%  South Africa: 89%  Brazil: 57%, 87%, 69%  Botswana: 54%, 53%, 58%  Nigeria: 58%  Kenya: 59% (Results from small studies with differing definitions of adherence) Adherence is equally problematic in resource-limited and resource-rich settings. No evidence shows that it is more problematic. Source: MTCT-Plus, Columbia University 2002

19. 19 Adherence to ART versus Adherence to Other Medications  Adherence to medications is a complicated issue, regardless of the illness or disease  In other chronic diseases like diabetes, hypertension, and heart disease, 20-80% of people are non- adherent  ART non-adherence comparable to other chronic illnesses  Overall, 40% to 60% of people taking ART are less than 90% adherent

20. 20 Introductory Case: Abebech (cont.) 3.If any doses of ART are missed, a change in ART regimen will be necessary FALSE A change in regimen should only be done when absolutely necessary. Although this patient has been taking her medication incorrectly, this does not mean that she has failed her regimen She should be counseled that she needs to take her medication as prescribed and should be given suggestions on how to avoid missing her morning dose

21. 21 Challenges of Adherence to ART  Does not cure HIV infection, therefore must be taken regularly life long  High pill burden  Requires near perfect adherence  Specific dietary and fluid instructions  Side effects: short and long term  Stigma

22. 22 Five Types of Non-adherers 1.Consistent Underdoser Regularly neglects to take one of the prescribed doses, such as the midday dose Regularly takes only some of the prescribed medications 2.Consistent Overdoser Regularly takes a drug more often or in larger doses than prescribed 3.Random Doser Takes the medications when she or he thinks of it

23. 23 Five Types of Non-adherers (2) 4.Abrupt Overdoser Does not take medications properly and then takes an overdose prior to a clinic visit Doubles up for missed doses 5.Tourist (takes “drug holidays”) Abruptly stops all medications for a few days or weeks Takes one day off per week

24. 24 Introductory Case: Abebech (cont.) 4.Taking less than the prescribed dose is an effective way to make ART last longer without going to the pharmacy FALSE Taking less than the prescribed dose will lead to drug levels that are too low to prevent viral replication. This will lead to treatment failure Every effort must be made to take ART as prescribed to ensure treatment success

25. 25 Factors Affecting Adherence  A variety of factors impact a patient’s ability to adhere to a prescribed treatment regimen: Patient variables Treatment regimen Disease characteristics Patient–provider relationship Contextual factors  Understanding these factors can increase providers’ attention to adherence

26. 26 Patient Variables  Socio-demographic factors Generally, socio-demographic factors do not predict adherence behavior Some studies reported the following correlates of poor adherence 1-4 Female sex Non-white race Younger age Lower income Lower literacy 1. Kleeberger CA, et al. JAcquir Immune Defic Syndr 2001. 2. Weidle P, et al.. J Acquir Immune DeficSyndr 1999. 3. Valdez L, et al. Arch Intern Med 1999. 4. Gifford A, et al. J AcquirImmune Defic Syndr 2000.

27. 27 Patient Variables (2)  Psychosocial factors: Consistent associations are found between certain psychosocial factors and adherence behavior Common predictors of non-adherence include: Depression/psychiatric illness 1 Active alcohol and substance use 1 Lack of perceived efficacy of ART 2 Lack of social support 1 Lack of knowledge 1 1. Ickovics, J. and Christina S. Meade, C. JAIDS 2002; 2. Horne R, et al. 39th ICAAC, 1999;.

28. 28 Treatment Regimen  Treatment regimen factors include: The number of pills prescribed (pill burden) The complexity of the regimen (dosing frequency, ease of administration, food instructions, etc) The short- and long-term medication side effects Cost and access to medications Degree of behavioral change required

29. 29 Disease Characteristics  Disease characteristics include: The stage and duration of HIV infection Associated opportunistic infections HIV-related symptoms  Reported predictors of poor adherence include: Lack of advanced disease 1 Lack of prior experience with opportunistic infections 2 1.Wenger N, et al. 6th Conference on Retroviruses and Opportunistic Infections, 1999. 2.Singh N. et al. AIDS Care 1996.

30. 30 Patient–Provider Relationship  The patient-provider relationship may influence adherence through: Patient's overall satisfaction and trust in the provider Patient's opinion of the provider's competence Provider's willingness to include the patient in treatment decisions Tone of the relationship (warmth, openness, cooperation, etc) Adequacy of referrals

31. 31 Contextual Factors  Focuses primarily on macro-level barriers such as: Medical practices Systemic issues Life situation issues Institutional systems

32. 32 Published Reasons for Missing Doses  Simply forgot40%  Slept through the dose37%  Away from home34%  Change in routine27%  Busy with other things22%  Too sick13%  Sick from side effects10%  Depressed 9% Source: Chesney (1997) ACTG-Adherence to Combination Therapy

33. 33 Published Reasons for Missing Doses (2)  Remember: The most common reason for missing doses is: ‘I FORGOT’ Always try to discover the reason for forgetting If several doses were missed, is there a pattern?

34. Strategies to Improve ART Adherence

35. 35 The Adherence Team  A team approach is needed to optimally maximize adherence  Should involve physicians, nurses, pharmacists, other health care providers, and family/friends of the patient when possible  Use the team to ensure the patient is committed to therapy, before beginning ART  Monitor adherence regularly over time, as a team

36. 36 Gabre-Kidan, T., M.D., I-TECH Sept 2003

37. 37 Methods for Improving Adherence  Patient education and counseling  Visual medication schedules (diary cards, calendars, pill charts)  Adherence devices Medication organizers (pillboxes, medisets) Reminder devices (alarm watches, beepers, mobile phones, etc.)  Buddy system (peer, friend, family)  Directly Observed Therapy (DOT)  Simplified treatment regimens  Incentives (food, transport, etc.)

38. 38 Improving Adherence: Before Initiation of Therapy  Pharmacists should educate patients on: Adherence Risk and benefits of ART Side effects of ART Drug interactions Reminder cues Engaging support Seeking help quickly if problems occur Lifelong commitment to therapy

39. 39 Improving Adherence: Before Initiation of Therapy (2) Don’t make assumptions about patient adherence: Ask questions and discuss solutions  “Do you know that the medicines must be taken for the rest of your life? Your life depends on taking them everyday, at the right time”  “If you stop, you will become ill (not immediately, but after months or years)”  “Do you know what resistance is?”  “Do you know you should not share these medicines with family or friends?”

40. 40 Improving Adherence: Before Initiation of Therapy (3)  “Have you told anyone that you are HIV-positive? Telling someone else who can help you take your medicines every day will help you remember”  “How far do you have to travel to the clinic, and do you think you can keep regular appointments here?”  Ask about stigma related to taking the pills  Check the patient’s clinic attendance – ask about reasons for missed appointments

41. 41  Make sure the patient is involved in the decision to start therapy  Determine other medical barriers to adherence  Manage or refer for management of adherence- limiting co-morbid conditions  Identify any potential drug interactions (with other drugs, natural medicines, or food)  Identify and address specific cultural and/or religious factors that may potentially affect adherence (e.g. fasting, traditional healers, etc) Improving Adherence: Before Initiation of Therapy (4)

42. 42  Try to use simple regimens Once or twice daily Avoid food restrictions or requirements if possible Use combination tablets where available  Clear & simple instructions Improving Adherence: Before Initiation of Therapy (4)

43. 43  Inform patient of devices that can assist them in taking their medications regularly Alarm devices (wrist watch or cell phone alarms) Pill boxes Associating doses with daily activities Other memory cues Leaving reminders around home or work Leave medications out where they can see them Improving Adherence: Before Initiation of Therapy (5)

44. 44  Develop strategies ahead of time for handling: Side effects Missed doses Change in routine (carry an extra dose of ARVs) Travel (time zones) Storage of medications Fear of taking medications in front of others  Encourage patients to talk with others about their experiences Improving Adherence: Before Initiation of Therapy (6)

45. 45  Let patients practice pill-taking behavior before starting ART with OI prophylaxis medications or candy  Consider short term Directly Observed Therapy (DOT)  Encourage social support  Improve patient self-efficacy  Involve the multidisciplinary team to counsel about adherence Improving Adherence: Before Initiation of Therapy (7)

46. 46 Remember  ART is NEVER an Emergency  Take time to educate the patient before starting therapy

47. 47 Maintaining Adherence  Adherence is a dynamic behavior  Adherence is affected by factors that change throughout a person’s life  Adherence levels will change over time

48. 48 Pill Fatigue…  Patients who have been on treatment for a some time may get tired of taking medications every day or feel overwhelmed—‘pill fatigue’  Decision to stop treatment should be discussed with a health care provider If medication is stopped, stop all pills at once to avoid the development of resistance

49. 49 Improving Adherence: After Initiation of Therapy  Close follow-up (necessary amount will vary by patient)  Ask patient to verbalize treatment regimen  Educate about adherence Re-emphasize importance of adherence at each visit, even in patients with good virologic control Review incidence & management of adverse effects often

50. 50 Improving Adherence: After Initiation of Therapy (2)  Patients should be checked for adherence issues at each visit  Adherence interventions may be similar to techniques listed for pre-therapy preparation Reminders Support structures  Increase monitoring procedures if there is any sign of adherence problems Home visits DOTS

51. 51 Improving Adherence: After Initiation of Therapy (3)

52. Methods of Monitoring Adherence

53. 53 Measuring Patient Adherence to Medications  Self reports  Pill counts  Pharmacy records  Biological markers  Electronic devices  Measuring drug levels

54. 54 Patient Self-Report of Missed Doses  Ask questions in a respectful and non-judgmental way  Ask in a way that makes it easier for patients to be truthful “Many patients have trouble taking their medications. What trouble are you having?” “Can you tell me when and how you take each pill?“ “When is it most difficult for you to take the pills?“ “It is sometimes difficult to take the pills every day and on time. How many have you missed (yesterday, last 3 days, last month)? “When was the last time you missed a dose?”

55. 55 Pill Counts  Providers count remaining pills during clinic visit  Problems Patients can dump pills prior to visit Promotes a sense of distrust between patient and provider  Unannounced pill counts Done at home Can be more reliable Feasibility?

56. 56 Tracking Pharmacy Refill History

57. 57 Individual Experiences with Adherence 1.Describe your own experience of taking medicines to your partner 2.How easy was it to find information about the medicines? 3.How easy was it to follow the instructions on how to take the medicines? 4.What made it easy or hard to take the medicines? Please respect requests for confidentiality

58. 58 Supporting Adherence  What are common reasons for non-adherence?  How can we as pharmacists or druggists help patients take their medications regularly as prescribed?  How can we track adherence for our patients so that we can recognize a problem with adherence ?

59. 59 Key Points  Antiretroviral (ARV) regimens are complex and multiple barriers to adherence exist  Serious potential consequences can result from non- adherence  Patient/family education and involvement is critical for successful treatment of HIV infection  The medical team (provider, pharmacist, nurse) and the patient must work together to promote optimal adherence to both HIV care and ARV regimens  The pharmacist plays a vital role in promoting adherence and offering techniques for improvement of adherence