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

Treatment Failure Clinical Trial

— RESPECT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03120065
• Other study ID #: 1601396087
• Status: Completed
• Phase: N/A
• Start date: April 24, 2017
• Est. completion date: August 30, 2018

Study information

• Verified date: July 2020
• Source: Indiana University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 499
• Est. completion date: August 30, 2018
• Est. primary completion date: August 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years to 19 Years

Eligibility

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

Related Conditions & MeSH terms

• Treatment Failure
• Viral Resistance

Intervention

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.

Locations

Country	Name	City	State
Kenya	Moi Teaching and Referral Hospital - AMPATH Center	Eldoret

Sponsors (3)

Lead Sponsor	Collaborator
Rachel Vreeman, MD, MS	Brown University, Moi University

Country where clinical trial is conducted

Kenya, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Viral Resistance	Blood samples will be analyzed for viral resistance testing, both for retrospective and prospective samples samples (TP1)	18 months
Secondary	Adherence MEMS	Adherence will be monitored via MEMS bottle caps	3 months
Secondary	Adherence CAMP	Adherence will be assessed via CAMP questionnaire	3 months
Secondary	Clinical Data: WHO stage	WHO stage will be analyzed for associations with viral resistance and treatment failure in this cohort.	6 years
Secondary	Clinical Data: Viral Load	Longitudinal viral loads will be analyzed for associations with viral resistance and treatment failure in this cohort.	6 years
Secondary	Clinical Data: Weight	Longitudinal weight will be analyzed for associations with viral resistance and treatment failure in this cohort.	6 years
Secondary	Clinical Data: Height	Longitudinal height will be analyzed for associations with viral resistance and treatment failure in this cohort.	6 years
Secondary	Clinical Data: Regimen	Longitudinal regimen will be analyzed for associations with viral resistance and treatment failure in this cohort.	6 years
Secondary	Clinical Data: Opportunistic Infections	Longitudinal opportunistic infections will be analyzed for associations with viral resistance and treatment failure in this cohort.	6 years
Secondary	Clinical Data: Disclosure Status	Longitudinal disclosure status will be analyzed for associations with viral resistance and treatment failure in this cohort.	6 years