Virologic Treatment Failure and Drug Resistance in HIV-infected Kenyan Children (RESPECT)
Condition: Viral Resistance; Treatment Failure
Study type: Interventional

Summary: 
      The primary objective of this study is to use a well-characterized pediatric AMPATH cohort,
      with detailed medication-taking, drug level, and clinical data, to longitudinally evaluate
      treatment failure and drug resistance to improve long-term care for HIV-infected children in
      Kenya and other RLS. Examining treatment failure and drug resistance emergence in children on
      ART and what factors impact these negative outcomes, will provide needed data to critically
      evaluate the efficacy of current ART, weight-based pediatric drug dosing guidelines, and
      recommendations for subsequent therapies. The objective is to specifically characterize how
      non-adherence leads to a lack of viral suppression and to drug resistance evolution, and how
      this characterization can inform interventions to improve adherence and increase treatment
      success.
    

Detailed description: 
      Resistance to antiretroviral therapy (ART) hampers effective treatment of pediatric HIV
      infection and can undermine long-term clinical care outcomes. In resource-limited settings
      (RLS), where 90% of the world's HIV-infected children live, the risk and impact of ART
      failure and resistance development are particularly significant due to limited treatment
      monitoring, restricted medication options and lifelong ART needs, from birth through
      adolescence and into adulthood. Children in RLS therefore face serious clinical consequences
      when their virus is not suppressed, but few longitudinal data are available to inform
      pediatric clinical guidelines or direct interventions to minimize those risks. How specific
      patterns of medication non-adherence or challenges with appropriate ART dosing might impact
      ART failure and the development of drug resistance are poorly understood for children in RLS.
      The primary objective of this study is to use a well-characterized pediatric AMPATH cohort,
      with detailed medication-taking, drug level, and clinical data, to longitudinally evaluate
      treatment failure and drug resistance to improve long-term care for HIV-infected children in
      Kenya and other RLS. Examining treatment failure and drug resistance emergence in children on
      ART and what factors impact these negative outcomes, will provide needed data to critically
      evaluate the efficacy of current ART, weight-based pediatric drug dosing guidelines, and
      recommendations for subsequent therapies. The objective is to specifically characterize how
      non-adherence leads to a lack of viral suppression and to drug resistance evolution, and how
      this characterization can inform interventions to improve adherence and increase treatment
      success. AMPATH cares for over 80,000 adult and pediatric HIV-infected patients in western
      Kenya, including over 2,800 children on ART.

      The research objective of this application will be accomplished by pursuing the following
      five specific aims: Aim 1: Determine prevalence of viral failure and examine resistance
      mutations among a retrospective study cohort of 685 perinatally HIV-infected Kenyan children
      on 1st-line ART; Aim 2: Investigate associations between specific adherence patterns, ART
      drug levels and other demographic and clinical factors, with viral failure and drug
      resistance; Aim 3: Study long-term immunologic, virologic and drug resistance outcomes and
      their associations in prospectively re-enrolled study participants; Aim 4: Enhance analyses
      of viral failure, drug resistance accumulation and associated demographic and clinical
      factors by examining the longitudinal banked samples available for a subset of the study
      cohort (n=327); Aim 5: Develop a data-driven intervention algorithm to identify children at
      risk for viral failure and resistance.

      The hypothesis of this study proposes that there will be high levels of treatment failure and
      drug resistance associated with patterns of non-adherence and inadequate drug levels.
    

Intervention name(s): Electronic Dose Monitoring (MEMS)
Intervention type(s): Other
Intervention description(s): The MEMS cap is an electronic bottle cap that records the time and date of a bottle being opened. The research personnel will extract the timing of the MEMS bottle opening events for adherence analysis.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: adherence