Adherence to Antiretroviral Therapy for Pediatric HIV Infection: A Review with Recommendations for R

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Adherence to Antiretroviral Therapy for Pediatric
HIV Infection A Review with Recommendations for
Research and Clinical Management

• Jane M. Simoni
• University of Washington
• NIMH/IAPAC International Conference
• on HIV Treatment Adherence
• Jersey City, New Jersey March 8-10, 2006

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Collaborators

• Arianna Montgomery, CDC
• Erin Martin, Childrens National Medical Center
• Michelle New, Childrens National Medical Center
• Penny Demas, Montefiore Medical Center
• Sohail Rana, Howard University

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Background

• Combination highly active antiretroviral therapy
  (HAART) can
• Suppress HIV
• Improve immune function
• Reduce morbidity and mortality
• Viral suppression requires
• High levels of adherence to therapy
• Most research has been conducted with adults
• Children
• Different approaches to the study of adherence
  and interventions to improve adherence are
  required
• Unique psychosocial, developmental, and
  pharmacologic issues in children and adolescents

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Aims of the Review

• Describe the advantages and disadvantage of
  various adherence assessment methodologies (with
  a focus on factors that impact pediatric
  populations)
• Summarize the empirical findings regarding
  estimates of adherence among pediatric patients
• Review the findings on correlates of adherence
• Describe empirically tested interventions to
  improve adherence

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Data Sources for the Review

• A thorough search published journal articles,
  abstracts, books, and ongoing studies on
  pediatric adherence to antiretroviral therapy
  (Pubmed, PsycINFO, Medline, AIDSLINE, and CRISP
• Combinations of the search terms (HIV/AIDS and
  pediatric/children and compliance/adherence) were
  used
• Through December, 2005.
• Hand searched references for relevant articles
• Input from colleagues
• Three reviewers narrowed down 252 citations to 53
  relevant to the objectives.

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• RESULTS

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1. Adherence AssessmentMethodologies

• Range of methodologies for capturing
  antiretroviral medication adherence.
• Direct methods
• biological assays of active drug, metabolite or
  other markers in bodily fluids
• Indirect methods
• self-report caregiver report clinician
  assessment medical chart review clinic
  attendance pill count pharmacy refill records
  electronic drug monitoring (EDM) behavioral
  observation (directly observed therapy) and
  therapeutic impact (HIV-1 RNA viral load (VL),
  CD4 lymphocyte count), Centers for Disease
  Control-defined stage of disease progression, and
  mortality.

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Adherence AssessmentMethodologies (cont)

• Assessing adherence in pediatric populations
  poses specific challenges (Brakis-Cott Mellins
  (2003) Dolezal et al., 2003. (Matsui, 2000).
• Medications only available in liquid form
  (precludes pill counts and EDM)
• Pre-packaged pill boxes or syringes
• Self-report cognitive abilities and
  developmental level
• Caregiver report vantage point varies depending
  on role (parent or guardian, other family member,
  babysitter, home health aide, or school nurse).
  Each may have incomplete information about the
  specifics of medication taking.
• No one individual is consistently the most
  reliable

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2. Estimates of Adherence

• Twenty-five studies reporting empirical data on
  pediatric adherence rates.
• Articles were mostly based on studies in the U.S.
  
• Sample sizes ranged from 6 to 161 participants (3
  months to 24 years of age).
• Most participants were infected perinatally.
• Adherence estimates varied widely but were
  generally suboptimal
• Comparisons complicated by different assessment
  methods
• Data on adherence estimates were collected mainly
  from patient and caregiver reports
• Few studies employed purportedly more objective
  methods such as EDM.

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Estimates of Adherence (cont)

• Comparison of assessment strategies (Wiener et
  al., 2004)
• Provider (i.e., clinical nurse) overestimated
  adherence.
• Self-reported adherence higher than provider
  ratings (social desirability).
• Patients who reported even one missed dose in the
  last week were at greater risk for of having a VL
  gt 10,000.
• Face-to-face interviews, quick and easy to
  administer.
• Intensive daily phone diary had similar validity
  to the self-report interview (VL), but expensive
  and burdensome
• VL is not a perfect indicator of adherence

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Factors Related to Adherence

• Adult typologies note variables related to the
  patient, disease, treatment regimen,
  patient-provider relationship, and clinical
  setting (Ickovics Meisler 1997 )
• But, for pediatric populations?
• Role of the caregiver
• Developmental challenges

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Factors Related to Adherence (cont)

• Caregivers
• May also be HIV-positive
• May have other co-morbidities and stressors
• Stigma associated with the diagnosis of HIV and
  the caregivers often inadequate resources to
  cope with the disease often mean taking
  medications and attending clinic appointments
  remain very low in the hierarchy of daily
  priorities in the life of the family

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Factors Related to Adherence (cont)

• Adolescents unique factors
• Marhefka et al. 2004. Adolescents have same
  difficulties as adults, but less autonomy,
  privacy, and mobility.
• Pugatch, 2002 (6 HIV teenagers aged 16-24 years)
  
• Unique factors involvement and the present
  orientation of youth.
• Trocme, 2002 (29 HIV-positive French adolescents)
  
• Unique factors Nonadherence way to express
  autonomy
• Adherence generally decreases as teenagers assume
  responsibility for their medication (Battles et
  al., 2002).

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Interventions and Strategies to Improve ART
Adherence Empirical Evidence of Efficacy

• Seven published studies that empirically
  evaluated interventions to enhance adherence
  among pediatric populations

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Berrien 2004

• Only RCT
• Home nursing visits (67 families) as a means of
  increasing adherence.
• Designed to identify and resolve barriers to
  medication adherence (e.g. pill swallowing
  training, other barriers not reported).
• Treatment group
• knowledge scores significantly improved (p lt .02)
• self-reported adherence marginally improved
  (p.07).

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Gigliotti 2001

• Directly observed therapy (DOT) intervention.
• To determine whether prolonged elevation of VL
  could be attributable to poor adherence.
• Found that DOT administered for 4-8 days
  significantly lowered the viral loads of all 6
  children in their sample.

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Roberts 2004

• Examined an intensive DOT program (6 families who
  showed continued high VL loads despite viral
  sensitivity and caregiver assertions of regular
  medication administration.)
• Home health nurse and DOT. Supplemented by
  intensive education and counseling during a 4-day
  hospitalization and post-discharge.
• Four of the six families responded with improved
  viral loads following the DOT hospitalization.

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Lyon 2003

• 12-week educational program (23 HIV-positive
  youths, aged 15-22 years, and 23 treatment
  buddies)
• 6 meetings with treatment buddy and 6 meetings
  with youths only (2 hours and included a meal).
• Devices (watches, pill boxes, and calendars) were
  introduced.
• Three months post-intervention
• 91 reported improved adherence, which case
  managers corroborated.
• None had a 1log reduction in VL to UD.
• Four participants indicated improved immune
  functioning.

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Rogers 2001

• Theory-driven intervention
• Based on Prochaskas Stages of Change model.
• Intensive 8-week program with video- and
  audio-tape material
• Assessed stage of readiness to adhere with HAART.
• Precontemplation, Contemplation, Preparation,
  Action/Maintenance, and Relapse.
• e.g. Precontemplation material addressed
  concerns about taking HAART.
• e.g. Preparation program practiced a regimen
  with surrogate pills for 1-2 weeks.
• Primarily for treatment-naïve subjects, prepare
  for successful initiation.
• Evaluation was hampered by high attrition (only
  18 of the 65 enrollees completed the full
  program), attributed to difficulties in
  scheduling program visits and the labor intensive
  intervention.

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Shingadia 2000

• Inserted a gastrostomy tube (GT) in 17 children
  on HAART who were at least mildly symptomatic.
• In year post-procedure
• Clinically significant improvement (gt2log VL
  reduction) in 10 cases
• All 17 patients were noted to be adherent by
  care providers.
• Attributed to initiation of a new medication
  regimen at time of procedure for all 10 who
  showed improvement
• Recommend that HAART regimen be changed after the
  GT placement to minimize the impact of viral
  resistance secondary to nonadherence.
• Parents reported
• GT tubes were well tolerated
• Reductions in medication administration time
• Improvement in child behavior during medication
  administration.

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Ellis 2006

• Multisystemic therapy, an intensive, home-based
  family therapy
• Conducted by retrospective chart review of 19
  children
• 90 of children and families referred to the
  program accepted the referral and 95 received a
  full dose of treatment, suggesting high program
  feasibility.
• Results
• Caregiver general HIV knowledge improved
  significantly
• Caregiver-reported adherence did not change
• VL were found to significantly decrease
  majority of children maintained these
  improvements during the 3 months after treatment
  termination.
• Results suggest that MST holds promise as an
  intervention for improving health outcomes among
  pediatric patients with HIV.

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2 Interventions in progress

• 1. Pediatric IMPACT
• Largest evaluation of a pediatric adherence
  intervention and randomized controlled trial
  (on-going, CDC-funded)
• HIV children lt13 and primary caregiver (New York
  City and Washington, D.C).
• Intervention Includes
• Adherence Coordinator, initial needs assessment,
  and tailored modular interventions (including
  home-based services).
• Randomly assigned to either a minimal or
  enhanced arm.
• EIG Six modules HIV education, HIV diagnosis
  disclosure education to children, behavior
  modification, medication swallowing, medication
  management, and referrals to social and mental
  health services.

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2. Adolescent Impact

• CDC-funded RCT of an intervention to improve
  adherence to care and treatment and reduce sexual
  transmission risk behavior in youth ages 13-21
  with HIV.
• The study is currently being conducted in five
  pediatric and adolescent clinics in New York
  City, Baltimore, and Washington DC.
• Adolescent impact provides education, social
  support and skills training through an integrated
  series of one-on-one and group sessions.
• 7group sessions address health and developmental
  issues common to youth with HIV
• 5 five one-on-one sessions are used to tailor
  prevention messages to the unique health and risk
  profile of each teen.
• Teens receive organizational tools including a
  personal digital assistant (PDA) with adherence
  software
• Optional home visit is also provided.

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Summary

• Researchers are using a range of strategies for
  measuring adherence, with patient self-report or
  caregiver reports the most frequently used
• Estimates of adherence across studies are low
• Nonadherence remains problematic
• Low levels of adherence are typical of pediatric
  populations with other chronic illnesses (Dolezal
  et al. 2003 Rapoff book 1999).
• Different measures and study methodologies
  complicate the comparisons
• Correlates of adherence are reported rather
  haphazardly
• As variables related to the medication/regimen,
  patient, or caregiver
• Overarching models for understanding correlates
  and predictors of adherence are noticeably
  lacking
• Literature on the development and formal
  evaluation of theory-driven strategies for
  improving adherence remains sparse

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Recommendations for Assessing Adherence

• Need for definitive guidelines for selecting
  appropriate assessment methods
• 2. Perhaps consider the use of multiple methods
  or triangulation.
• Methods other than self-report may be too
  unreliable, burdensome, or costly
• 4. Simple question (doses were missed in the
  last week) may be sufficient (Wiener et al.,
  2004 Simoni, J. M.(in press)
• 5. Getting valid self-reports of pediatric
  adherence may depend on honesty, respect, time
  to talk privately, and ability to listen well.
  (Strug et al. 2003)

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Recommendations for Improving Adherence

• 1. Empirical studies provide
• Utility and efficacy of DOT, a 12-week
  educational program, gastrostomy tube insertion,
  and nursing home visits
• However, findings were preliminary and Ns small
• Adherence to the intervention itself was often
  problematic.
• 2. Other studies provide
• Strategies that rely on clinical practice wisdom
  and lack formal evaluation (Pontali et al 2005)

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Recommendations for Future Research

• Focus on evaluating the validity and reliability
  of self-report adherence measures
• Comparing self-report to more objective measures
  or clinical indicators are needed to identify the
  most cost-effective assessment strategy (Wiener
  et al., 2004).

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Recommendations for Future Research

• 3. Investigate adherence levels and potential
  correlates of adherence
• Should incorporate prospective studies (HAART
  initiation)
• Steele and Grauer advise systematically examining
  factors that may predict adherence and developing
  risk profiles to target potential non-adherers.
• Further examination of factors related to
  caregivers
• Development and evaluation of adherence models
  that incorporate multiple domains of
  influence.(multi-site studies and the
  incorporation of non-U.S.-based sites)

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Recommendations for Future Research

• 4. Interventions to enhance adherence
• Need to be theory-based and empirically tested
• Need to go beyond cognitive intervention and
  education and counseling (Pugatch, 2002) and will
  be long-term (Brackis-Cott, 2003)
• 5. Need to expand work in international settings
  and resource-constrained environments

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• Thank you