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Adherence, Resistance and Antiretroviral Therapy


Adherence, Resistance and Antiretroviral Therapy. Lucille Sanzero Eller, PhD, RN ... 2. Describe assessment of determinants of adherence to ART. ... – PowerPoint PPT presentation

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Title: Adherence, Resistance and Antiretroviral Therapy

Adherence, Resistance and Antiretroviral Therapy
  • Lucille Sanzero Eller, PhD, RN
  • Associate Professor
  • Rutgers, The State University of New Jersey
  • College of Nursing
  • A Local Performance Site of the NY/NJ AETC
  • June 2008

Objectives (1)
  • 1. Define adherence.
  • 2. Describe assessment of determinants of
    adherence to ART.
  • 3. Discuss nursing strategies to promote
    adherence to ART

Objectives (2)
  • 4. Describe resistance to ART.
  • 5. Discuss evaluation of adherence.

Primary Goals of ART
  • Maximal and durable viral suppression
  • Restoration and preservation of immune function
    (CD4 count)
  • Improved quality of life
  • Reduced HIV-related opportunistic infections
  • Reduced morbidity and mortality

Adherence Definition
  • Right drug
  • Right amount
  • dose (formulation), total duration, intervals
  • Right circumstances
  • e.g., with or without food, not with certain
    other drugs
  • Adapted from Second International Conference on
    Improving Use of Medicines, 2004. Retrieved

Adherence (1)
  • 95 adherence is necessary to achieve viral
    suppression of therapy, but more-potent NNRTI regimens lead to
    viral suppression at moderate levels of adherence
  • Bangsberg, D.R. (2006). Less Than 95 Adherence
    to Nonnucleoside Reverse-Transcriptase Inhibitor
    Therapy Can Lead to Viral Suppression. Clinical
    Infectious Diseases. 43, 939941.

Adherence (2)
  • Although viral suppression may be possible with
    moderate adherence, the probability of viral
    suppression and reduced disease progression and
    mortality improves with every increase in
    adherence level
  • Bangsberg, D.R. (2006). Less Than 95 Adherence
    to Nonnucleoside Reverse-Transcriptase Inhibitor
    Therapy Can Lead to Viral Suppression. Clinical
    Infectious Diseases. 43, 939941.

Adherence (3)
  • Assess the determinants of adherence
  • prior to initiation of ART
  • within first few days of initiation of ART
  • at each visit to assess any change in

Determinants of Adherence (1)
  • Individual Factors
  • Sociodemographics
  • Basic Needs
  • food, shelter, heating, cooling, refrigeration
  • Economic Factors
  • health insurance, prescription coverage,
    employment status, disability insurance, income
  • Education
  • language, literacy, health literacy
  • Cultural beliefs, values, practices

Determinants of Adherence (2)
  • Individual Factors
  • Cognitive Factors
  • cognitive impairment, forgetfulness, confusion
  • Psychological Factors
  • depression, anxiety
  • Substance Abuse
  • drug and alcohol use
  • Note Changes in appearance, behavior, eye
  • or speech may indicate any of the above

Determinants of Adherence (3)
  • ART Regimen and Treatment Experience
  • side effects
  • early toxicity
  • complexity of regimen
  • food restrictions
  • history of reasons for non-adherence
  • history of missed medical appointments

Determinants of Adherence (4)
  • Disease characteristics
  • symptoms
  • immune status
  • illness severity
  • Social support
  • disclosure status with friends family
  • support from friends
  • family support
  • partner support

Determinants of Adherence (5)
  • Patient-provider relationship
  • provider competence
  • trust
  • communication
  • adequacy of referrals
  • inclusion of patient in decision-making

Determinants of Adherence (6)
  • Informational resources
  • Education and information about ARVs, side
  • Health care environment
  • Access- insurance, transportation,
  • Convenience
  • Confidentiality
  • Adherence services at site of medical care

Determinants of Adherence (7)
  • Health beliefs
  • purpose of treatment
  • effectiveness of treatment
  • treatment experiences
  • self-efficacy
  • Poorest adherers impaired, substance abusers
  • (Levine et al., 2005)

Patient Readiness for HAART
  • Health Belief Model can be used to assess
    readiness and likelihood of adherence to Highly
    Active Antiretroviral Therapy (HAART)

Health Belief Model Concepts (1)
  • Perceived susceptibility the individuals belief
    that she is susceptible to HIV disease
  • Perceived severity the individuals belief that
    HIV disease progression has serious consequences

Health Belief Model Concepts (2)
  • Perceived benefits the individuals belief that
    adherence to ART would reduce susceptibility to
    HIV disease progression or disease severity
  • Perceived barriers the individuals belief that
    the materials, physical and psychological costs
    of adhering to ART outweigh the benefits

Health Belief Model Concepts (3)
  • Cues to action the individuals exposure to
    factors that prompt adherence to ART
  • Self-efficacy the individuals confidence in her
    ability to successfully adhere to ART

Health Belief Model and Adherence
Individual Factors Demographics, lifestyle,
social support, mental health, substance use
Perceived benefits and barriers ofART
Perceived susceptibility of HIV disease
progression Perceived severity of HIV disease
Perceived threat of non-adherence
Likelihood to engage in adherence behavior
Cues to action
Self-efficacy for adherence
Strategies to Promote Adherence (1)
  • Lifestyle
  • Identify instances when med side effects might
    interfere with lifestyle (job, family)
  • Fit regimen to lifestyle, preference and
  • consider daily schedule, weekly or monthly
    changes in schedule
  • Balance dosing ease with strength of regimen
  • ideal is highest potential viral suppression
    acceptable to patient

Strategies to Promote Adherence (2)
  • Social support/Provider support
  • Establish therapeutic/trusting,
    non-judgmental/confidential patient-provider
    relationship prior to initiating therapy
  • Identify reinforce sources of emotional and
    social support
  • Educate patient and support persons, if
    available, on the regimen prescribed
  • Dosage, side effects, side effect management,
    food requirements

Strategies to Promote Adherence (3)
  • Social support/Provider support (cont.)
  • Utilize community resources
  • Support groups, peer mentors
  • Collaborate with multidisciplinary team and
    refer as needed
  • Case management for entitlements, transportation
  • Substance abuse counselor
  • Mental health counselor

Strategies to Promote Adherence (4)
  • Social support/Provider support (cont.)
  • Provide contact information to reach health care
  • Reinforce seeking expert advice when stopping ARV
  • Formulate an individual plan of care for
    follow-up visits and phone calls
  • Assess side effects of therapy within first few
    days of initiation of therapy
  • Assess accuracy of understanding of regimen
  • within first few days of initiation of therapy

Strategies to Promote Adherence (5)
  • Mental health and Substance Use
  • Provide treatment and referral as needed for
    mental health and substance use before initiating

Strategies to Promote Adherence (6)
  • Perceived susceptibility
  • Provide culturally and linguistically appropriate
    education and counseling on disease process of
  • Assist patient in developing accurate perception
    of risk of non-adherence
  • Tailor risk information to individuals beliefs,
  • Perceived severity
  • Explain adherence in reference to
  • resistance

Strategies to Promote Adherence (7)
  • Perceived benefits
  • Provide specific information re dose, schedule
    and dietary requirements of ART and potential
    benefits of adherence
  • Graph patients viral load and CD4 count before
    and throughout treatment to trend response for
    reinforcement of benefits of adherence
  • Utilize team approach with nurses, physicians,
    pharmacists and peer counselors

Strategies to Promote Adherence (8)
  • Perceived barriers
  • Address patient questions and concerns with
    specific information and strategies to address
    barriers (e.g., regimen complexity, dietary
    restrictions, short and long term side effects)
  • Provide incentives for adherence
  • Provide ongoing support and reassurance
  • Provide and instruct patient how maintain a daily
    pill diary to identify barriers to adherence

Strategies to Promote Adherence (9)
  • Perceived barriers (cont.)
  • Anticipate and discuss potential side effects,
    their duration and management
  • Simplify regimens, dosing and food requirements
  • Include patient in development of plan of
    care/decision-making process
  • Establish readiness to start therapy

Strategies to Promote Adherence (10)
  • Cues to action
  • Provide detailed, specific, easily understood
    information re when and how to take medication
  • Provide and instruct patient in the use of tools
    to foster and reinforce adherence
  • beepers, watches, pill organizers, stickers,
    telephone reminders, medication planner, written
    instructions, instruct to place medications in
    location where they will be seen
  • Utilize educational aids including charts,
    cartoons, written information

Strategies to Promote Adherence (11)
  • Cues to action (cont.)
  • Provide adherence assessment and counseling at
    routine medical visits
  • Enlist friends/family/partner to provide
    motivation and remind patient to take medications
  • Collaborate with patient to choose a regular
    daily activity as a cue to take medication
    (getting out of bed, making breakfast or dinner)

Strategies to Promote Adherence (12)
  • Self-efficacy
  • Provide skill building for adherence
  • role-playing (e.g. patient-provider communication
    skills use of jelly beans to practice taking
    medications on schedule)
  • problem solving (what to do for late or missed
  • planning ahead for refills
  • management of medications during changes in daily
  • potential side effects, self-management
    strategies, when to call the health care provider

Strategies to Promote Adherence (13)
  • Self-efficacy (cont.)
  • Collaborate with patient on potential solutions
    for patient-identified barriers to adherence.
  • Provide positive reinforcement for adherence.
  • Contract with patient for adherence.
  • Utilize role models with adherent behavior
  • Utilize the problem-solving process (e.g. ask the
    patient Think of a time when you might miss a
    dose of your medication. What would you do

  • The ability of HIV to enter the cell and
    replicate despite presence of antiretroviral
  • Can lead to increasing viral load, ongoing damage
    to immune system, progression of HIV disease

Reasons for Resistance
  • High rate of HIV replication (109 to 1010
  • Error prone HIV polymerase
  • Selective pressure and mutant viral strains are
    cause of resistance

Selective Pressure
  • ARTs suppress replication of wild type (original)
    virus while ART-resistant mutant virus continues
    to replicate

  • Development of resistance to a drug in a
    particular class may transfer to drugs in the
    same class
  • Limits options for ART

Adherence/Resistance Relationship
  • Highly Active Antiretroviral Therapy (HAART)
    Observational Medical Evaluation and Research
    (HOMER) study
  • 1191 ARV naïve adults receiving 2 NRTIs plus a PI
    or NNRTI
  • Found bell-shaped relationship between level of
    adherence and drug-resistance mutations
  • (Harrigan et al., 2005 )

Adherence/Resistance Relationship (Harrigan et
al., 2005)
Primary ARV Resistance (1)
  • Patient who is ARV naïve is infected with
    ARV-resistant virus
  • Single or multi-class drug resistance increasing
  • Primary resistance in 10 North American cities
    (Little et al. 2002)
  • 3.4 1995-1998
  • 12.4 1999-2000

Primary ARV Resistance (2)
  • Prevalence of primary drug resistant HIV
    mutations varies geographically (Wolf, 2006)
  • San Francisco 26
  • Spain 19
  • European multicenter study 10
  • Guidelines recommend resistance testing prior to
    ART initiation (USDHHS, 2004 EuroGuidelines
    Group for HIV Resistance, 2001

Primary ARV Resistance (3)
  • RESINA project Germany 2001-03
  • Effects of pre-treatment resistance testing and
    tailored first-line HAART treatment decisions
    based on this genotype testing
  • N269, 48 weeks after initiation of
    genotype-guided HAART
  • Comparable efficacy of first-line HAART in groups
    with resistant HIV and wild-type HIV

Resistance Testing
  • 2 Types of assays
  • Phenotypic
  • Genotypic
  • Both types of assay require presence of a minimum
    amount of HIV
  • Tests may not detect resistance at viral load
    below 500-1000 copies/ml
  • Test may not detect minority mutations, those

  • Direct quantification of drug sensitivity
  • Increasing concentrations of drug added to
    patient HIV cultures
  • Viral replication compared to that of wild-type
  • The IC50 is concentration of drug that inhibits
    viral replication by 50
  • Disadvantages
  • Lengthy procedure
  • Costly

  • Indirect measure of drug resistance
  • Genetic code of patient virus is compared to
    that of wild-type virus
  • Resistance is defined by number of known
    resistant mutations (those associated with
    reduced drug sensitivity) present in patient
    sample at time of test

Virtual Phenotyping
  • Predicts the phenotype from the genotype
  • Patients genotypic mutations are compared with a
    database of samples of paired genotypic and
    phenotypic data
  • IC50 of matching viruses are averaged, and the
    likely phenotype of patient virus identified
  • Advantages
  • requires less time than phenotyping
  • less costly than phenotyping

Adherence Studies (1)
  • Multicenter AIDS Cohort Study (MACS)
  • N539 77 taking 3 or more medications
  • Reasons for non-adherence by frequency
  • Forgot, change in daily routine, busy, away from
  • To avoid side effects, slept, ran out of meds,
    felt depressed or ill, felt the drug was
    toxic/harmful, dont want to take pills
  • Too many pills to take, instructions conflicted,
    didnt want others to notice, had problem taking
    pills (Kleeberger et al, 2001)

Adherence Studies (2)
  • Most patients willing to tolerate severe side
    effects, large pill burden, inconvenience for
    higher potency of ART
  • (Miller et al., 2002 Sherer et al., 2005)

Adherence Studies (3)
  • Phone interviews for patient preferences and
    priorities re ART (N387)
  • Lower viral load, higher CD4, durability of viral
    suppression were more important than resistance
    profile, GI side effects, dosing frequency and
    pill burden
  • 92 preferred more effective, 89 preferred more
    durable 2X day regimen to more convenient 1X day
  • (Sherer et al., 2005)

Adherence Studies (4)
  • Review of 24 ART adherence interventions
  • The most effective adherence interventions
    targeted patients with known or anticipated
    adherence problems
  • improvements held over time
  • (Amico, Harman Johnson, 2006)

Evaluation of Adherence (1)
  • Adherence to ART declines over time
  • Ongoing assessment and intervention critical
  • Self-report is primary means of assessment

Evaluation of Adherence (2)
  • Use non-judgmental language and tone of voice.
  • the patient who senses disapproval and is shamed
    for non-adherence is less likely to provide
    accurate information
  • Be aware of non-verbal communication.
  • facial expression, posture, tone of voice,
    seating arrangement, use of personal space

Evaluation of Adherence (3)
  • Ask questions in a way that gives permission for
    missed doses.
  • Which doses are the hardest to remember to
    take? Which doses did you miss?
  • Use open-ended questions.
  • Can you tell me about how you take your
    medicines on a typical weekday?
  • How do you take your medicines on a weekend

Evaluation of Adherence (4)
  • Communicate the understanding that problems with
    adherence are expected.
  • Normalization of adherence problems opens door
    for honest communication.
  • Many people have difficulty sticking to their
    medication schedule. What problems have you had
    with taking your medications?

Evaluation of Adherence (5)
  • Engage patient in problem-solving and alternative
    scenarios to address specific problems with

Evaluation of Adherence (6)
  • Ask permission to provide information and
    feedback to lower patient resistance to the
  • Can I give you some suggestions that may help
    with that problem?
  • Can I tell you how taking your medications on
    time can keep you healthy?

Evaluation of Adherence (7)
  • When providing information, keep it simple.
  • Stress and anxiety lower the ability to
    assimilate new information.
  • Assess understanding of new information by asking
    patients to repeat it in their own words.

Clinical Evaluation of Adherence
  • Level of HIV RNA in plasma
  • CD4 lymphocyte count
  • Clinical condition of patient
  • Resistance testing

Key Points (1)
  • Adherence
  • Right drug
  • Right amount
  • dose (formulation), total duration, intervals
  • Right circumstances
  • 2. Optimal adherence to ART 95 or more of all
    prescribed doses taken on time

Key Points (2)
  • 3. Determinants of Adherence
  • Individual factors
  • ART regimen and treatment experience
  • Disease characteristics
  • Social support
  • Patient-provider relationship
  • Informational resources
  • Health care environment

Key Points (3)
  • 4. Health Belief Model can be used to assess
    readiness for ART and develop strategies to
    promote adherence
  • Perceived susceptibility
  • Perceived severity
  • Perceived benefits
  • Perceived barriers
  • Cues to action
  • Self-efficacy

Key Points (4)
  • 5. Resistance- the ability of HIV to enter the
    cell and replicate in the presence of ARVs
  • 6. Resistance testing- identifies drugs to which
    the virus is not resistant
  • Phenotyping
  • Genotyping
  • Virtual phenotyping

Key Points (5)
  • 7. Evaluation of adherence
  • Adherence declines over time
  • Ongoing evaluation and intervention critical
  • Self-report is primary means of evaluation
  • 8. Clinical evaluation of adherence
  • Level of HIV RNA
  • CD4 lymphocyte count
  • Clinical condition of patient
  • Resistance testing