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Adherence Evaluation & Interventions In HIV Care



The single most important aid to adherence is the use of a pillbox.


Antiretroviral adherence in the range of 95-100% is essential for effectiveness and durability of antiretroviral therapy. 

The development of antiretroviral resistance results from subtherapeutic concentrations of antiretroviral therapy as a result of nonadherence.  The development of resistance is in most cases a lifelong issue.


Therefore, it is critical that prior to initiation of therapy and frequently while on therapy, providers should assess patient's adherence and knowledge of the importance of adherence.


Adherence to medications may be best evaluated by some combination of the following:


1.  Pharmacy records

2.  Pill counts

3.  Nonjudgmental and direct questioning of patients: "How many doses did you miss in the last month?" or "How many doses MIGHT you have missed in the last month?"

4.  Attendance records to clinic visits

5.  Therapeutic drug monitoring
6.  And, ultimately by HIV virologic suppression in the absence of resistance, malabsorption, and pharmacologic issues that reduce antiretroviral drug levels


When significant nonadherence is identified, an etiology for the nonadherence should be elucidated if possible.  This issue can then be addressed specifically, e.g., timers for falling asleep, pill boxes for medication away from home, extra supplies of medication for work, etc.


In the author's experience the most common causes of medication nonadherence in the motivated patient are as follows:


1.  Falling asleep prior to a late evening dosing

2.  Being away from home at medication dosing time without a supply of medication at the patient's disposal

3.  Refrigeration of one medication
4.  Intolerable side effects that produce a disincentive with each dose


See Table 1. below for common causes of medication, appointment and refill nonadherence and some suggestions for intervention.  Education about the importance of adherence is a key component of any of these suggested interventions.


Because of the possible permanent sequelae of nonadherence, either >95% adherence should be expected prior to initiation or achieved after initiation of therapy OR antiretroviral therapy should be withheld or withdrawn until completion of an intensive adherence intervention which might include the following:


1.  Patient education regarding the critical nature of adherence and ways to facilitate adherence (alarms, reminders, pill boxes, etc.). 

2.  Evaluation of patient's level of literacy: is the patient able to read and understand medication dosing instructions?

3.  Education of patient about common issues in medication administration: "twice daily" dosing = closer to every 12 hours and not every 6 or 8 hours, "three times daily" dosing = closer to every 8 hours and not every 6 hours; "on an empty stomach" = at least 1 hour before meals or at least 2 hours after meals, etc.

4.  Enlistment of support from friends, caretakers, relatives to assist the client in increasing their adherence

5.  Conduct a detailed review of the client's nonadherence with analysis of the specific barriers to adherence experienced by the patient followed by a plan designed to overcome those specific barriers.

6.  Consider patient education regarding the "all or none" concept: patients should take every dose, every day or stop all antiretroviral therapy until they can do so.  This provides a valid, simplified concept that can be applied to medication outages, drinking binges, or episodes of nausea and vomiting.
7.  Patients should be instructed in filling a weekly pill box in advance and using this is a guide to their adherence.

8.  Patients should obtain a portable pill box which can be carried with them in case they are away from home.  Obviously this is difficult for liquid medications or medications that require refrigeration.

9.  Doses of medication should be kept at place of employment or other places where scheduled dosing occurs if possible.


If antiretroviral resistance has developed for whatever reasons to prior therapy, consideration could be given to restarting that therapy for an analysis of nonadherence and/or interventions for adherence.


Studies of adherence have revealed a variety of factors to correlate with adherence to antiretroviral therapy:


1.  Availability of emotional and practical life supports

2.  Ability of the patients to fit the medication into their daily routine

3.  The understanding the nonadherence leads to resistance

4.  The recognition that taking all drug doses is important

5.  Feeling comfortable taking medications in front of people

6.  Good doctor-patient relationship


Predictors of nonadherence may include the following:1,2


1.  Living alone or unsupervised

2.  Few previous hospitalizations

3.  Treatment causes many unpleasant side effects

4.  Treatment regime is complex

5.  Treatment regime (especially medication) is long-term

6.  A history of nonadherence
7.  A history of alcohol use

8.  Lack of social support


A comprehensive literature review of medication adherence may be found HERE.  A variety of interventions may be useful, but none have been found to have universal applicability or effectiveness.


Table 1.  Nonadherence and suggested interventions
Underpinning all of these interventions is the patient's understanding of the critical importance of adherence.
Nonadherence to medication dosing
"I fall asleep before my late dose" Suggest to set an alarm clock or watch.

Suggest that a friend call or wake the patient up if the patient is asleep at medication time.
Suggest that the patient take the dose in question earlier in the day
Suggest that the patient take the dose in question with the most temporally related meal if possible
Suggest to take the early dose of the day a bit earlier so that the late dose is also a bit earlier

"I forgot my medicine at home" Carry a pill box with at least one dose of all medications in it
Store a small supply of medication at usual locations patient might frequent e.g. work, relatives' and friends' home
"I get side effects from the medication" Evaluate and treat the side effects definitively.  Inquire about efficacy of such therapy frequently.
If the side effects are not treatable, change medications to eliminate this side effect
[patient's meal schedule does not allow for appropriate dosing of meal-dependent medications] Encourage the patient to set his meal schedule based on his medication schedule.
Consider medication modifications to eliminate meal-dependence of medications, e.g., boosted indinavir instead of unboosted indinavir, substitution of abacavir for didanosine, substitution of fosamprenavir for indinavir, etc.
"I cannot take medication at work" Suggest that the patient use the restroom as an excuse to take medication.

Design a regimen that does not require dosing at the patient's place of employment.
Recommend to patient to consider confiding in a supervisor so that medication dosing can be attained at work.

"I ran out of medications" Determine cause of medication outage and intervene appropriately.
Suggest that the patient call the pharmacy for refills one week in advance.
Encourage use of a weekly pill box and filling the pillbox a week in advance.  When medication bottles are within 1 week of being empty, ask patient to call pharmacy for refills
Develop a system of mailing refills if possible.
Synchronize all of patient's antiretroviral medication refills (as well as other medication refills) to prevent the necessity for multiple trips to the pharmacy each month.
"I forgot the one medication in the refrigerator" Suggest the following:

Place a note on the pillbox reminding the patient about  the refrigerated medication.
Place all medications in the refrigerator if possible
Place all medications by the refrigerator if possible.

[chronic or binge alcohol or drug use] Brainstorm as to how to take medications during drug or alcohol use
Modify patient's regimen to include safety with respect to the concomitant administration of drugs and/or alcohol
Enroll patient in rehab, 12-Step Group, or Harm Reduction support group
Nonadherence to clinic visits
"I forgot about my appointment" Build a positive and supportive therapeutic relationship.

Provide patient with printed appointment date at each visit.
Remind patient via mail or telephone regarding upcoming appointments.
Encourage patient to get a date book or a PDA.
Enroll a friend as an adherence assistant.
Reward the patient for attendance with food or other rewards.

"I cannot leave my kids alone" Develop a clinic area for temporary child care while the mother or father is being seen.
"I have to work" Schedule visits when patient's schedule allows (e.g., evening clinic, weekends, etc.)
Consider possible adjustments in work schedule
Consider disability benefits if appropriate
"I cannot wait to be seen at clinic.  I have to get back to work." Schedule patient as the first visit of the day.
Make special efforts to expedite patient's care.
"I work all night and sleep all day." See the patient on their weekend equivalent or see the patient as the first appointment or last appointment of the day.
[patient gets to clinic too late to be seen] See the patient even if it involves inconvenience to provider. 
Brainstorm ways to get the patient to present on time based on reason for being late. 
Or, just accept that due to unchangeable factors, that the patient will be late.  For example if the patient is driving from out of town, allow the patient to be seen on a less rigid schedule.
[patient is unable to pay for services] Refer to Social Services to explore community resources for indigent clients.
Encourage fiscal responsibility and budgeting for healthcare and co-pays.
[no transportation to clinic] Refer to Social Services to explore Case Management and community resources for transportation.  Consider providing bus tokens or cab vouchers.
[poor comfort or confidentiality issues in the waiting area] Attempt to identify and address the specific issues raised by the client or indicate why the problem areas cannot be addressed.
[repeatedly missing clinic appointments due to "cable TV addiction" or other strange or unlikely explanations] Consider thorough Social Services evaluation, and if not helpful, consider urine toxicology testing to identify occult addictive disorder.
Quick Menu / Table of Contents
Introduction Principles Management NRTI Info NNRTI Info
PI Info Fusion Inhibitors Coreceptor Inhibitors Integrase Inhibitors Drug Summary
Coformulation Antiretroviral Therapy
Investigational Adherence Lab Evaluation Resistance Tests PEP
Antiretroviral Tables OI Prevention Vaccinations TB Therapy Hepatitis Therapy
OI Diagnosis OI Therapy Bibliography Links Palliative Therapy


Updated 1/18/2013


1 National Electronic Library for Health: Mental Health, Encouraging Adherence to Treatment, http://www.nelmh.org/content_show.asp?c=1&fid=7&fc=001006

2 Murphy DA, Marelich WD, Hoffman D, Steers WN. Predictors of antiretroviral adherence. AIDS Care. 2004 May;16(4):471-84.