Optimizing Viral Load Suppression in Kenyan Children on Antiretroviral Therapy (Opt4Kids)

• ClinicalTrials.gov Identifier: NCT03820323
• Recruitment Status: Active, not recruiting
• First Posted: January 29, 2019
• Last Update Posted: December 6, 2019
• Sponsor: University of Washington
• Collaborators: National Institute of Mental Health (NIMH); Kenya Medical Research Institute; University of Colorado, Denver
• Information provided by (Responsible Party): Rena Patel, University of Washington

Tracking Information

• First Submitted Date: January 23, 2019
• First Posted Date: January 29, 2019
• Last Update Posted Date: December 6, 2019
• Actual Study Start Date: March 7, 2019
• Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 25, 2019)

Rates of viral suppression [ Time Frame: 12 months after point-of-care viral load testing ]

Viral Load <1000 copies/mL at 12 months after point-of-care viral load testing

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 25, 2019)

• Time to viral suppression [ Time Frame: 12 months post enrollment ]
  Time needed to viral suppression among those children without viral suppression at their 1st POC VL testing or newly initiating ART after POC VL testing implementation.
• Feasibility of POC VL testing [ Time Frame: Every 3 months within the 12 months study period ]
  The proportion of children undergoing VL testing within each group at the scheduled intervals.
• Turn-around time for the VL testing results [ Time Frame: Every 3 months within the 12 months study period ]
  The time it takes for viral load results to be received by health care providers and participants.
• Retention-in-care [ Time Frame: 12 months after point-of-care viral load testing ]
  proportion of children in care at the end of the study
• Proportion of children switched to 2nd line ART [ Time Frame: 12 months after point-of-care viral load testing ]
  Proportion of children on 2nd line ART tab the 12- month study visit
• Time to switch to 2nd line ART [ Time Frame: 12 months post enrollment ]
  The time it takes to switch to 2nd line ART after Virological failure
• Proportion of children with drug resistance mutations (DRMs) [ Time Frame: 12 months post enrollment ]
  The proportion of children tested for DRMs with significant mutations within each class of HIV drugs.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Optimizing Viral Load Suppression in Kenyan Children on Antiretroviral Therapy
• Official Title: Optimizing Viral Load Suppression in Kenyan Children on Antiretroviral Therapy
• Brief Summary: Among nearly 1 million HIV-infected children receiving antiretroviral treatment (ART), as many as 40% of those living in resource limited settings have not achieved virologic suppression. Kenya, a UNAIDS fast-track and PEPFAR priority country, has an estimated 98,000 children aged 0-14 years living with HIV. Virologic suppression is achieved by only 65% of Kenyan children on ART translating to only 38% of the final UNAIDS 90-90-90 goal for population-level viral suppression. Feasible, scalable and cost-effective approaches to maximizing durability of first-line ART and ensuring viral load (VL) suppression in HIV-infected children are urgently needed. This pilot study will evaluate two critical components related to viral suppression in children via: 1) Point-of-care (POC) VL testing (Aim 1) and 2) targeted DRM testing (Aim 2) among children on first-line ART at three facilities within a PEPFAR-funded HIV care and treatment program in Kenya. The hypotheses are: 1) viral suppression rates will be higher among children with access to POC VL testing and time to suppression shorter compared to children with standard VL testing and 2) DRM testing will shorten time to viral suppression and that the investigators will observe high levels of 1st line antiretroviral DRMs among children on ART without viral suppression. This proposal directly addresses the urgent need to find interventions to maximize viral suppression among children on ART and achieve the UNAIDS 90-90-90 goals.

Detailed Description

The study design will be a randomized, controlled study to pilot the use of POC VL and DRM testing in children aged 1-14 years on first-line ART. Children enrolling at each site will be randomized 1:1 to two study arms.

Standard of Care Arm:

Participants in the Standard-of-Care (SOC) control arm will receive the standard-of-care VL and DRM testing based on the existing Kenyan national guidelines. VL testing will be 6 months after ART initiation (then every 3 months if unsuppressed, otherwise every 12 months) with DRM testing only if failing second-line ART. Children who have a high lab-based HIV VL (≥1,000 copies/mL) will receive intensive adherence counseling and be asked to return to the clinic in 3 months for repeat HIV VL testing. If the HIV VL remains high (≥1,000 copies/mL), the children will be managed per Kenya national guidelines.

Intervention Arm:

Children in the intervention arm will undergo POC VL testing every 3 months for a total of 12 months. "Targeted" DRM testing will include DRM testing for each child on the first detection of lack of viral suppression (VL > 1000 copies/mL) and in children newly initiating ART.

The investigators will follow the viral outcomes 12 months after the implementation of POC VL testing and compare VL suppression rates, defined as VL <1000 copies/mL by the Kenyan national guidelines, among intervention vs. control arms, accounting for pre-intervention VL suppression rates.

The primary outcome for Aim 1 is rates of viral suppression (defined as VL <1000 copies/mL) at 12 months after POC VL testing implementation at the three facilities. The secondary outcome for Aim 1 is time to viral suppression among those children without viral suppression at their 1st POC VL testing or newly initiating ART after POC VL testing implementation. In Aim 2, the investigators intend to evaluate the impact of targeted HIV DRM testing on viral suppression in the intervention arm only. The investigators will also explore how sociodemographic, behavioral, clinical, and facility factors may be contributing to the DRM patterns they observe.

• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Randomized control trial of two study arms

Masking: Double (Investigator, Outcomes Assessor)
Masking Description:

Investigators and those conducting the analysis will be blinded to arm allocation

Primary Purpose: Diagnostic

• Condition: Chronic HIV Infection

Intervention

Diagnostic Test: POC VL and targeted DRM testing.

Point-of-care Viral Load Testing will be done to ensure that providers and caregivers receive the results with in 24 hours study. Targeted DRM testing will be performed during the initiation of ART and when viremia (VL>1000 copies/mL) is detected.

Study Arms

• No Intervention: Standard of Care
  Participants in the Standard-of-Care control arm will receive laboratory based VL testing based on the existing Kenyan national guidelines. DRM testing will be done if there is a failing 2nd line ART regimen based on the current Kenyan guideline.
• Experimental: Intervention
  POC VL and targeted DRM testing.
  Intervention: Diagnostic Test: POC VL and targeted DRM testing.

• Publications *: Patel RC, Oyaro P, Odeny B, Mukui I, Thomas KK, Sharma M, Wagude J, Kinywa E, Oluoch F, Odhiambo F, Oyaro B, John-Stewart GC, Abuogi LL. Optimizing viral load suppression in Kenyan children on antiretroviral therapy (Opt4Kids). Contemp Clin Trials Commun. 2020 Oct 27;20:100673. doi: 10.1016/j.conctc.2020.100673. eCollection 2020 Dec.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: December 4, 2019): 704
• Original Estimated Enrollment (submitted: January 25, 2019): 700
• Estimated Study Completion Date: December 2020
• Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Children aged 1-14 years living with HIV (documented HIV positive)
• On first-line ART per Kenyan National Guideline or
• Newly initiating ART

Exclusion Criteria:

• On second-line, third-line, or non-standard first-line ART

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Year to 14 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Kenya

Administrative Information

• NCT Number: NCT03820323
• Other Study ID Numbers: STUDY000004861; R34MH115769 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: De-identified individual participant data for all outcome measures will be made available after study completion
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: After primary outcomes results are published.
• Access Criteria: Contact PIs of the study and obtain institutional ethic review approvals.

• Responsible Party: Rena Patel, University of Washington
• Study Sponsor: University of Washington

Collaborators

• National Institute of Mental Health (NIMH)
• Kenya Medical Research Institute
• University of Colorado, Denver

Investigators

• Principal Investigator: Rena Patel, MD, MPH; University of Washington
• Principal Investigator: Lisa L Abuogi, MD, MSc; University of Colorado, Denver

• PRS Account: University of Washington
• Verification Date: December 2019