Virologic Treatment Failure and Drug Resistance in HIV-infected Kenyan Children (RESPECT) (RESPECT)

Virologic Treatment Failure and Drug Resistance in HIV-infected Kenyan Children

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.

Study Overview

• Status: Completed
• Conditions: Treatment Failure; Viral Resistance
• Intervention / Treatment: Other: Electronic Dose Monitoring (MEMS)

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.

• Study Type: Interventional
• Enrollment (Actual): 499
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Kenya
  • Eldoret, Kenya, 30100
    • Moi Teaching and Referral Hospital - AMPATH Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 19 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Previous enrollment in CAMP study
• Viable banked blood sample; HIV-infected documented by DNA-PCR (Amplicor, Roche, Basel, Switzerland) for children less than 18 months of age and by 2 parallel HIV rapid ELISA tests using Determine and Bioline for children older than 18 months of age.
• < 19 years of age

Exclusion Criteria:

Mental or physical incapacity of legal caregiver leading to inability to provide informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: MEMS follow up; Approximately 25% of the enrolled study population will have their adherence to medicines monitored by research personnel through the use of electronic dose monitoring caps (MEMS) for a period of 3 months. The participant's ART medication regimen will be dispensed in a bottle with a cap that monitors the time and date in which the cap is opened. Each month, the participant will bring the bottle with them on their clinic day for three months and the research personnel will extract the timing information from the cap.

Other: Electronic Dose Monitoring (MEMS); 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Viral Resistance	Blood samples will be analyzed for viral resistance testing, both for retrospective and prospective samples samples (TP1)	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adherence MEMS	Adherence will be monitored via MEMS bottle caps	3 months
Adherence CAMP	Adherence will be assessed via CAMP questionnaire	3 months
Clinical Data: WHO stage	WHO stage will be analyzed for associations with viral resistance and treatment failure in this cohort.	6 years
Clinical Data: Viral Load	Longitudinal viral loads will be analyzed for associations with viral resistance and treatment failure in this cohort.	6 years
Clinical Data: Weight	Longitudinal weight will be analyzed for associations with viral resistance and treatment failure in this cohort.	6 years
Clinical Data: Height	Longitudinal height will be analyzed for associations with viral resistance and treatment failure in this cohort.	6 years
Clinical Data: Regimen	Longitudinal regimen will be analyzed for associations with viral resistance and treatment failure in this cohort.	6 years
Clinical Data: Opportunistic Infections	Longitudinal opportunistic infections will be analyzed for associations with viral resistance and treatment failure in this cohort.	6 years
Clinical Data: Disclosure Status	Longitudinal disclosure status will be analyzed for associations with viral resistance and treatment failure in this cohort.	6 years

Collaborators and Investigators

• Sponsor: Rachel Vreeman, MD, MS
• Collaborators: Brown University; Moi University
• Investigators: Principal Investigator: Rachel C Vreeman, MD, MS, Indiana University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2017
• Primary Completion (Actual): August 30, 2018
• Study Completion (Actual): August 30, 2018

Study Registration Dates

• First Submitted: March 6, 2017
• First Submitted That Met QC Criteria: April 13, 2017
• First Posted (Actual): April 19, 2017

Study Record Updates

• Last Update Posted (Actual): July 22, 2020
• Last Update Submitted That Met QC Criteria: July 20, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: adherence
• Other Study ID Numbers: 1601396087

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No