Optimizing Viral Load Suppression in Kenyan Children on Antiretroviral Therapy

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Optimizing Viral Load Suppression in Kenyan Children on Antiretroviral Therapy

Conditions
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Chronic HIV Infection

Intervention / Treatment
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* Diagnostic Test: POC VL and targeted DRM testing.
* Diagnostic Test: SOC VL testing


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 14 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized control trial of two study arms
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Standard of Care<br>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<br>* 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.<br>* Other names: Kenyan National guidelines for viral load testing;|
| Experimental: Intervention<br>POC VL and targeted DRM testing. | Diagnostic Test: POC VL and targeted DRM testing.<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Viral Suppression | Viral Load <1000 copies/mL at 12 months after enrollment | 12 months after enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Virological Suppression at 12 Months Among Children Newly Initiating ART or Initially Virologically Unsuppressed | Among children newly initiating ART or initially virologically unsuppressed, we then evaluated the virological suppression status at 12 months post-enrollment. | 12 months post enrollment | 
| Number of Participants Who Underwent POC VL Testing | The number of children undergoing VL testing within each group (POC VL testing or SOC VL testing) at the scheduled intervals. | Every 3 months within the 12 months study period | 
| Turn-around Time for the VL Testing Results | The time it takes for viral load results to be received by health care providers and participants. | Every 3 months within the 12 months study period | 
| Number of Children With Any or Major Drug Resistance Mutations (DRMs) | The number of children tested for DRMs with any or major mutations within each class of HIV drugs. | 12 months post enrollment |