This document discusses strategies to promote adherence to antiretroviral therapy (ART). It begins with a case study of a patient, Abebech, who is not taking her ART correctly. The document then covers the importance of adherence to ART, challenges to adherence, and methods for assessing and improving adherence. Key strategies discussed for improving adherence include patient education, counseling, visual schedules, reminder devices, the buddy system, and simplified treatment regimens. The pharmacist's role in adherence includes assessing barriers, developing strategies to promote adherence, monitoring adherence over time, and counseling patients.

1. Adherence to ART
Unit 14
HIV Care and ART: A Course for
Pharmacists by Salahadin M.Ali

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. A lot of doses have to be missed 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
 Describe the role of the pharmacist in adherence
for ART

7. 7
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

8. 8
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

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 and treatment
failure
 Prevents development of opportunistic infections
 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
 Transmission of HIV to others
 Transmission of resistant virus to the community
 Higher costs to the individual and ART program
• Increase in morbidity and mortality ,Secondary health
costs & Medication wastage

11. 11
Introductory Case: Abebech (cont.)
1. A lot of doses have to be missed before ART
becomes ineffective
FALSE
 Taking less than the prescribed doses leads to reduced
virologic control
 Counsel the patient on the need for adherence
 Recommend that she gets a follow-up CD4 or TLC count
every 3 months to detect drug failure

12. Adherence by Pill
Count, %
NNRTI Group, % PI Group, %
94 to 100 ~90 ~65
74 to 93 ~ 75 ~60
54 to 73 ~ 60 ~30
0 to 53 ~30 ~12
Viral Load Suppression and Adherence:
NNRTI vs. PI

13. Virologic Control Falls with Diminished
Adherence
Bangsberg DR et al. 12th CROI, 2005; abstract 616
PI
NNRTI
0-53 54-73 74-93 94-100
0
20
40
60
80
100
%
VL
<
400
copies/mL
% Adherence (Pill Count)
0-53 54-73 74-93 94-100
0
20
40
60
80
100
% Adherence (Electronic Measurement)

14. 14
Adherence and Antiretroviral
Drug Resistance
 Sub-optimal adherence predisposes to resistance:
Association between poor adherence and
antiretroviral resistance is well-documented1,2
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. 10% Adherence difference = 21% change in risk of progressing to AIDS
Adherence and AIDS-Free Survival
Bangsberg D, et al. AIDS. 2001:15:1181
Proportion
AIDS-Free
Months from Entry
P = .0012
0 5 10 15 20 25 30
0.00
0.25
0.50
0.75
1.00
Adherence
90–100%
50–89%
0–49%

17. 17
Introductory Case: Abebech (cont.)
2. ART must be taken as prescribed to avoid the
development of resistance and possible treatment
failure
TRUE

18. 18
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 day1
 >33% report missing doses in the past 2 to 4 weeks1
 Partly due to non-adherence, ART fails in
approximately half of patients for whom it is
prescribed2
1. Ickovics, J.R. et al., JAIDS, 2002..
2. Valdez L, et al., Arch Intern Med, 1999.

19. 19
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

20. 20
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 is comparable to other chronic
illnesses
 Overall, 40% to 60% of people taking ART are less
than 90% adherent

21. 21
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

22. 22
Challenges of Adherence to ART
 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
 Adverse effects: short and long term
 Stigma

23. 23
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

24. 24
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

25. 25
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

26. 26
Factors Affecting Adherence
 A variety of factors impact a patient’s ability to
adhere to a prescribed treatment regimen:
 Patient variables
 Patient–provider relationship
 Treatment regimen
 Disease characteristics
 Contextual factors
 Understanding these factors can increase
providers’ attention to adherence

27. 27
Patient Variables
 Socio-demographic factors
 Generally, socio-demographic factors do not predict
adherence behaviour
 Some studies reported the following correlates of poor
adherence1-4
• Female sex
• Younger age
• Lower income
• Lower literacy
 Nondisclosure of HIV status, with accompanying stigma and
isolation

28. 28
Patient Variables (2)
 Psychosocial factors:
 Consistent associations are found between certain
psychosocial factors and adherence behavior
 Common predictors of non-adherence include:
• Depression/psychiatric illness1
• Active alcohol and substance use1
• Lack of perceived efficacy of ART2
• Lack of social support1
• Lack of knowledge1
 Spirituality

29. 29
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

30. 30
Treatment Regimen
 Treatment regimen 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 adverse effects
 Cost and access to medications
 Degree of behavioural change required

31. 31
Disease Characteristics
 Disease characteristics include:
 The stage and duration of HIV infection
 Associated opportunistic infections
 HIV-related symptoms
 N.B. Reported predictors of poor adherence
include:
• Lack of advanced disease1
• Lack of prior experience with opportunistic infections2
1. Wenger N, et al. 6th Conference on Retroviruses and Opportunistic Infections, 1999.
2. Singh N. et al. AIDS Care 1996.

32. 32
Contextual Factors
 Focuses primarily on macro-level barriers such as:
 Medical practices
 Systemic issues
 Life situation issues
 Institutional systems

33. Published Reasons for
Missed Doses
 Simply forgot/too busy 52%
 Away from home 46%
 Change in routine 45%
 Depressed/overwhelmed 27%
 Took drug holiday/medication break 20%
 Ran out of medication 20%
 Too many pills 19%
 Felt drug was too toxic 18%
 Wanted to avoid other adverse effects 17%
Gifford AL, et al. J Acquire Immune Defic Syndr. 2000;23:386-395.

34. 34
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?

35. Strategies to Improve
ART Adherence

36. 36
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

37. 37
ART Care Model
(Adherence Protocol)
Multidisciplinary (Team) effort:
Patient
Physician
Nursing
Nutritionist
Pharmacist
Social worker
TGK/ITECH/9.0
Gabre-Kidan, T., M.D., I-TECH Sept 2003

38. Role of the pharmacist in Adherence
 Identifying barriers to adherence before a patient
begins therapy and suggest possible solutions with
the patient and /or other health care workers
 Assessing patient adherence and follow up
 Developing strategies to promote adherence
 Monitoring adherence for patients overtime
 Counseling patients

39. 39
Methods for Improving ART 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.)

40. 40
Improving Adherence:
Before Initiation of Therapy
 Pharmacists should educate patients on:
 Adherence
 Risk and benefits of ART
 Adverse effects of ART
 Drug interactions
 Reminder cues
 Engaging support
 Seeking help quickly if problems occur
 Lifelong commitment to therapy

41. 41
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?”

42. 42
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

43. 43
 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)

44. 44
 Try to use simple regimens
 Once or twice daily
 Avoid food restrictions or requirements if possible
 Use fixed dose combination tablets where available
 Clear & simple instructions
Improving Adherence:
Before Initiation of Therapy (5)

45. 45
 Inform patient of devices that can assist them in
taking their medications regularly
 Alarm devices1 (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 (6)

46. 46
 Develop strategies ahead of time for handling:
 Adverse 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 (7)

47. 47
 Let patients practice pill-taking behavior before
starting ART with OI prophylaxis medications or
candy
 Consider short term Directly Observed Therapy
(DOT)4,5
 Encourage social support
 Improve patient self-efficacy
 Involve the multidisciplinary team to counsel about
adherence
Improving Adherence:
Before Initiation of Therapy (8)

48. 48
Remember
 Cautions should be taken before starting ART
 Take time to educate the patient before starting
therapy

49. 49
Maintaining Adherence
 Adherence is a dynamic behaviour
 Adherence is affected by factors that change
throughout a person’s life
 Adherence levels will change over time

50. 50
Pill Fatigue…
 Patients who have been on treatment for 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

51. 51
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

52. 52
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

53. 53
Improving Adherence: After Initiation of
Therapy (3)

54. Methods of Monitoring
Adherence

55. 55
Measuring Patient Adherence to
Medications
 Self reports
 Pill counts
 Pharmacy records
 Biological markers
 Electronic devices
 Measuring drug levels

56. 56
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?”

57. 57
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?

58. 58
Tracking Pharmacy Refill History

59. 59
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 ?

60. 60
Key Points
 Antiretroviral (ARV) regimens are complex and have 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