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

• ClinicalTrials.gov Identifier: NCT03820323
• Recruitment Status: Completed
• First Posted: January 29, 2019
• Results First Posted: December 27, 2022
• Last Update Posted: December 27, 2022
• 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

Study Description

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 The Joint United Nations Programme on HIV/AIDS (UNAIDS) fast-track and The U.S. President's Emergency Plan for AIDS Relief (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 drug resistance mutation (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.

Condition or disease	Intervention/treatment	Phase
Chronic HIV Infection	Diagnostic Test: POC VL and targeted DRM testing.; Diagnostic Test: SOC VL testing	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 704 participants
• 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
• Official Title: Optimizing Viral Load Suppression in Kenyan Children on Antiretroviral Therapy
• Actual Study Start Date: March 7, 2019
• Actual Primary Completion Date: December 31, 2020
• Actual Study Completion Date: December 31, 2020

Arms and Interventions

Arm	Intervention/treatment
Standard of Care; Participants in the Standard-of-Care control arm will receive laboratory based VL testing based on the existing Kenyan national guidelines by routine clinical staff (not study staff). DRM testing is usually done if there is a failing 2nd line ART regimen based on the current Kenyan guideline.	Diagnostic Test: SOC VL testing; SOC VL testing is done at 6 months after ART initiation then every 3 months if unsuppressed, otherwise every 12 months. DRM testing is conducted only if failing 2nd line ART.; Other Name: Kenyan National guidelines for viral load testing
Experimental: Intervention; POC VL and targeted DRM testing.	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.

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Viral Suppression [ Time Frame: 12 months after enrollment ]
   Viral Load <1000 copies/mL at 12 months after enrollment

Secondary Outcome Measures :

1. Virological Suppression at 12 Months Among Children Newly Initiating ART or Initially Virologically Unsuppressed [ Time Frame: 12 months post enrollment ]
   Among children newly initiating ART or initially virologically unsuppressed, we then evaluated the virological suppression status at 12 months post-enrollment.
2. Number of Participants Who Underwent POC VL Testing [ Time Frame: Every 3 months within the 12 months study period ]
   The number of children undergoing VL testing within each group (POC VL testing or SOC VL testing) at the scheduled intervals.
3. 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.
4. Number of Children With Any or Major Drug Resistance Mutations (DRMs) [ Time Frame: 12 months post enrollment ]
   The number of children tested for DRMs with any or major mutations within each class of HIV drugs.

Eligibility Criteria

• Ages Eligible for Study: 1 Year to 14 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Kenya

Rtcp-Faces

Kisumu, Kenya

Sponsors and Collaborators

University of Washington

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

  Study Documents (Full-Text)

Documents provided by Rena Patel, University of Washington:

Study Protocol  [PDF] March 2, 2022

Statistical Analysis Plan  [PDF] March 11, 2022

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Patel RC, Oyaro P, Thomas KK, Wagude J, Mukui I, Brown E, Hassan SA, Kinywa E, Oluoch F, Odhiambo F, Oyaro B, Kingwara L, Karauki E, Yongo N, Otieno L, John-Stewart GC, Abuogi LL. Point-of-care HIV viral load and targeted drug resistance mutation testing versus standard care for Kenyan children on antiretroviral therapy (Opt4Kids): an open-label, randomised controlled trial. Lancet Child Adolesc Health. 2022 Oct;6(10):681-691. doi: 10.1016/S2352-4642(22)00191-2. Epub 2022 Aug 18.

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.

• Responsible Party: Rena Patel, Assistant Professor, Division of Allergy and Infectious Disease, Department of Medicine, University of Washington
• ClinicalTrials.gov Identifier: NCT03820323
• Other Study ID Numbers: STUDY000004861; R34MH115769 ( U.S. NIH Grant/Contract )
• First Posted: January 29, 2019
• Results First Posted: December 27, 2022
• Last Update Posted: December 27, 2022
• Last Verified: December 2022

Individual Participant Data (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; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); 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.

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

Additional relevant MeSH terms:

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases