Adherence to Antiretroviral Therapy Access to antiretroviral therapy (ART) transforms HIV/AIDS management into coordina

1. Measuring Pediatric Adherence to Antiretroviral Therapy in Western Kenya. Rachel C. Vreeman, MD, MS; Winstone M. Nyandiko, MBChB, MMED; Samwel O. Ayaya, MBChB, MMED; Edward A. Liechty, MD; David G. Marrero, PhD; Thomas S. Inui, ScM, MD AMPATH RESEARCH SITES RESEARCH CONTRIBUTION HIGHLIGHTS OVERVIEW • Adherence to Antiretroviral Therapy • Access to antiretroviral therapy (ART) transforms HIV/AIDS management into coordinating care of a complex chronic disease • 90% of the world’s 2.5 million HIV-infected children live in resource-limited settings unaccustomed to chronic disease management • Central challenge is to sustain high levels of adherence to ART to prevent viral resistance and opportunistic infections • To best sustain and improve adherence, we need to know who is adherent and who struggles with adherence • Indiana University – Kenya Partnership offers ideal “laboratory” in which to study pediatric ART adherence and ART dosing • Research Objective: To identify how to measure pediatric adherence to antiretroviral therapy (ART) in resource-limited settings (RLS) • Systematic Review of Pediatric ART Adherence in Low- and Middle-Income Countries • Systematic review to identify and critically review all existing pediatric ART adherence estimates, adherence measurement techniques, and correlates of adherence in RLS • More than 2/3 of studies from RLS reported >75% ART adherence • However, heterogeneous and unvalidated measures used to estimate adherence • Pediatric Adherence and Correlated Factors Among Children in AMPATH • Study Objective: To estimate current status of pediatric ART adherence and clinic adherence in AMPATH • Study Design: Used multivariable logistic regression to assess factors associated with increased odds of ART or clinic nonadherence • Of 1516 children on ART, 71% of AMPATH pediatric patients reported perfect ART adherence • Only 33% of children had both parents alive when started ART • Odds of reporting ART nonadherence increased for children with both parents dead (OR=1.48; 95% CI: 1.04 to 2.10), as well as for children on ART for ≥12 months or with ≥6 adherence measurements • 57% of children had imperfect clinic adherence • Qualitative Inquiry into Factors Sustaining Pediatric Adherence in Western Kenya • Study Objective: To identify key factors contributing to pediatric ART adherence in western Kenya • Study Design: Conducted 10 focus group discussions and 35 key-informant interviews with 120 parents and guardians of HIV-infected children on ART at four AMPATH urban and rural clinic sites • Assessed experience of having children take ART and factors inhibiting or facilitating ART adherence • Found that sustained adherence to ART depends on multiple cultural and environmental determinants • Determinants include critical factors operating at levels of individual child, parent/caregiver, household, community (including tribe, extended family, neighbors, and church), healthcare system, and society. • Based on these determinants, developed conceptual model for pediatric ART adherence • Impact of Kenyan Post-Election Crisis on Pediatric ART Adherence and Return to Clinic • Study Objective: To describe immediate impact of recent humanitarian crisis following disputed elections in Kenya on return to clinic and ART adherence for HIV-infected children. • Study Design: Mixed methods analysis that included retrospective cohort analysis and key informant interviews with pediatric healthcare providers • Majority of children, 93%, returned to clinical care in 4 months following elections • Reported perfect ART adherence dropped from 98% to 95% following elections (p<0.001) • Children on ART were significantly more likely to return to clinic than those not on ART • Members of tribes targeted by violence and members of minority tribes were less likely to return • In qualitative analysis, prominent barriers to return to clinic and adherence included concerns for personal safety, shortages of resources, changing priorities, and hopelessness • Pharmacokinetics of Nevirapine (NVP) in Children Co-Varying with Adherence and Nutritional Status • Study Objective: To establish the feasibility of pediatric pharmacokinetics modeling, body water composition assessment, and comprehensive pediatric adherence measurement • Study sample: 20 HIV-infected children ages 3-13 years initiating ART including NVP at 1 AMPATH clinic • Children given NVP in medication event monitoring (MEMS®) bottles for adherence assessment • At 2 weeks and 4 months after initiating ART, children hospitalized for overnight assessment: • Plasma NVP concentrations drawn for pharmacokinetics modeling • Body water composition measurements using deuterated water dosing and sampling • Comprehensive adherence assessment, including questionnaire, med measure, MEMS • Complete physical examination • Anticipated Outcomes: Will establish feasibility of using rapid, automated enzyme immunoassay to measure NVP plasma concentrations and of using MEMS® caps with liquid medications in Kenya setting. Will also establish pharmacokinetics model for pediatrics in resource-limited settings. • Progress To Date: All 20 children recruited, all using MEMS®. Over half of inpatient pharmacokinetics assessments complete. First batch of NVP assays run in AMPATH laboratory. RESOURCES • Children’s Health Services Research (CHSR) • Section of the Department of Pediatrics at Indiana University School of Medicine (IUSM) • Focuses on research in underserved pediatric populations, health policy research, clinical decision analysis, and using information and technology to improve children’s healthcare • Started in 2001 under the direction of Dr. Stephen Downs • In 2002, CHSR awarded $2.5 million from Anne E. Dyson Foundation to create a “laboratory” for research and education in community pediatrics • 9 full-time faculty and over $4 million in grants beyond initial funding • The Regenstrief Institute (RI) • Informatics and healthcare research organization established in 1969 in close affiliation with IUSM • Dedicated to improving health through research that enhances the quality and cost-effectiveness of health care • Over 120 staff, including 24 full-time investigators and 32 affiliated investigators • Academic Model for the Prevention and Treatment of HIV/AIDS (AMPATH) • Formed in 2000 as collaboration of IUSM, Moi University School of Medicine, & Moi Teaching and Referral Hospital in Eldoret, Kenya • AMPATH is the most rapidly expanding, highest quality, and cost-effective HIV/AIDS care program in sub-Saharan Africa • Operates 18 sites, employing >600 clinicians and staff • Have enrolled over 80,000 HIV-infected adults and children, with over 55,000 active patients • 48% of adult patients on combination ART (free through AMPATH) • 13,802 patients are ≤14 years, with 2,866 currently on ART • Designed and implemented sub-Saharan Africa’s first outpatient electronic medical record system, which tracks patients for clinical and research purposes • IU-Kenya Partnership and AMPATH have received over $106 million in funded grants and contracts to date • AMPATH Research Network • Highly organized, multinational research network undergirding AMPATH research program directed by Dr. Bill Tierney • AMPATH investigators include faculty from IUSM and Purdue • AMPATH Pediatric Research Working Group dedicated to improving healthcare for children in Kenya through research AMPATH Clinic Sites in Western Kenya. AMPATH Centre located in Eldoret (1). Ward 12 of Moi Teaching and Referral Hospital in Eldoret, Kenya. Setting and Study Personnel for AMPATH Inpatient Pediatric Pharmacokinetics Studies. CONTACT INFORMATION Rachel C. Vreeman, MD, MS Faculty Scholar, Indiana CTSI Assistant Professor of Pediatrics, Children’s Health Services Research, Indiana University School of Medicine Co-Director of Pediatric Research, Indiana University – Kenya Partnership E-mail: rvreeman@iupui.edu Phone: 317-278-0552