Viral ResistanceRESPECTNCT03120065
Virologic Treatment Failure and Drug Resistance in HIV-infected Kenyan Children (RESPECT)
A study testing Electronic Dose Monitoring (MEMS) in people with Viral Resistance and Treatment Failure, run by Rachel Vreeman, MD, MS at 1 site in Kenya.
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. Read more about this study
- Who is it for?
- Ages 4 to 19 years
- Conditions the study is for
- Viral Resistance, Treatment Failure
- What is being tested?
- Electronic Dose Monitoring (MEMS)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 499 participants
- Where
- 1 siteKenya
- Study dates
- 24 Apr 2017to 30 Aug 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 19 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- Mental or physical incapacity of legal caregiver leading to inability to provide informed consent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Viral Resistance, Treatment Failure
- Being tested
- Electronic Dose Monitoring (MEMS)
- Keywords
- adherence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Electronic Dose Monitoring (MEMS)Other
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.
| Study group | Role | What they receive |
|---|---|---|
| MEMS follow up | Other | 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. Receives: Other: Electronic Dose Monitoring (MEMS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Viral Resistance
Blood samples will be analyzed for viral resistance testing, both for retrospective and prospective samples samples (TP1)
Measured: 18 months
Secondary outcomes (9)
Adherence MEMS
Adherence will be monitored via MEMS bottle caps
Measured: 3 months
Adherence CAMP
Adherence will be assessed via CAMP questionnaire
Measured: 3 months
Clinical Data: WHO stage
WHO stage will be analyzed for associations with viral resistance and treatment failure in this cohort.
Measured: 6 years
Clinical Data: Viral Load
Longitudinal viral loads will be analyzed for associations with viral resistance and treatment failure in this cohort.
Measured: 6 years
Clinical Data: Weight
Longitudinal weight will be analyzed for associations with viral resistance and treatment failure in this cohort.
Measured: 6 years
Clinical Data: Height
Longitudinal height will be analyzed for associations with viral resistance and treatment failure in this cohort.
Measured: 6 years
Clinical Data: Regimen
Longitudinal regimen will be analyzed for associations with viral resistance and treatment failure in this cohort.
Measured: 6 years
Clinical Data: Opportunistic Infections
Longitudinal opportunistic infections will be analyzed for associations with viral resistance and treatment failure in this cohort.
Measured: 6 years
Clinical Data: Disclosure Status
Longitudinal disclosure status will be analyzed for associations with viral resistance and treatment failure in this cohort.
Measured: 6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2017
- Study start24 Apr 2017
- Primary completion30 Aug 2018
- Study completion30 Aug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Viral ResistanceStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 499 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rachel Vreeman, MD, MS
- Sponsor type
- University, hospital or other
- Collaborators
- Moi University, Brown University
- Responsible party
- Sponsor-investigator, Rachel Vreeman, MD, MS, Indiana University
- Investigators
- Rachel C Vreeman, MD, MS, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03120065
- Sponsor's protocol ID
- 1601396087
- Acronym
- RESPECT
- Status last verified
- Jul 2020
- First submitted
- 6 Mar 2017
- Last updated
- 22 Jul 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Virologic Treatment Failure and Drug Resistance in HIV-infected Kenyan Children
- ClinicalTrials.gov ID
- NCT03120065
- Acronym / sponsor ID
- RESPECT / 1601396087
- Conditions
- Viral Resistance, Treatment Failure
- Keywords
- adherence
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 499 participants (actual)
- Lead sponsor
- Rachel Vreeman, MD, MSUniversity, hospital or other
- Collaborators
- Moi University, Brown University
- Study start
- 24 Apr 2017 (actual)
- Primary completion
- 30 Aug 2018 (actual)
- Study completion
- 30 Aug 2018 (actual)
- First posted
- 19 Apr 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MEMS follow up | Other | Other: Electronic Dose Monitoring (MEMS)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. |
Who may qualify
- Ages
- 4 to 19 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (1 listed)
- Mental or physical incapacity of legal caregiver leading to inability to provide informed consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Other | MEMS follow up |
Primary outcome
Viral Resistance
Time frame: 18 months
Blood samples will be analyzed for viral resistance testing, both for retrospective and prospective samples samples (TP1)
9 secondary outcomes
Adherence MEMS
Time frame: 3 months
Adherence CAMP
Time frame: 3 months
Clinical Data: WHO stage
Time frame: 6 years
Clinical Data: Viral Load
Time frame: 6 years
Clinical Data: Weight
Time frame: 6 years
Clinical Data: Height
Time frame: 6 years
Clinical Data: Regimen
Time frame: 6 years
Clinical Data: Opportunistic Infections
Time frame: 6 years
Clinical Data: Disclosure Status
Time frame: 6 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rachel C Vreeman, MD, MS principal investigator
Indiana University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Electronic Dose Monitoring (MEMS) in people with Viral Resistance and Treatment Failure, run by Rachel Vreeman, MD, MS at 1 site in Kenya.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Kenya. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Viral Resistance (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2020.