Clinical trial NCT03120065: Virologic Treatment Failure and Drug Resistance in HIV-infected Kenyan Children (RESPECT)
Official title: Virologic Treatment Failure and Drug Resistance in HIV-infected Kenyan Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Viral Resistance
Treatment Failure
Keywords: adherence
Lead sponsor: Indiana University
Sponsor class: OTHER
Collaborators: name: Moi University
name: Brown University
First posted: 2017-04-19
Enrollment: 499
Sex: ALL
Minimum age (years): 4
Maximum age (years): 19
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief 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.

Eligibility criteria: 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

Primary outcomes:
measure: Viral Resistance
timeFrame: 18 months
Secondary outcomes:
measure: Adherence MEMS
timeFrame: 3 months
measure: Adherence CAMP
timeFrame: 3 months
measure: Clinical Data: WHO stage
timeFrame: 6 years
measure: Clinical Data: Viral Load
timeFrame: 6 years
measure: Clinical Data: Weight
timeFrame: 6 years
measure: Clinical Data: Height
timeFrame: 6 years
measure: Clinical Data: Regimen
timeFrame: 6 years
measure: Clinical Data: Opportunistic Infections
timeFrame: 6 years
measure: Clinical Data: Disclosure Status
timeFrame: 6 years
Other outcomes:
Locations:
city: Eldoret
country: Kenya
facility: Moi Teaching and Referral Hospital - AMPATH Center
Study officials:
affiliation: Indiana University School of Medicine
name: Rachel C Vreeman, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: