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| ID | Type | Description | Link |
|---|---|---|---|
| R34MH115769 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Mental Health (NIMH) | NIH |
| Kenya Medical Research Institute | OTHER |
| University of Colorado, Denver | OTHER |
| University of Washington |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Standard of Care | Other | 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. |
|
| Intervention | Experimental | POC VL and targeted DRM testing. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| POC VL and targeted DRM testing. | Diagnostic Test | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Viral Suppression | Viral Load <1000 copies/mL at 12 months after enrollment | 12 months after enrollment |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Rena Patel, MD, MPH | University of Alabama at Birmingham | Principal Investigator |
| Lisa L Abuogi, MD, MSc | University of Colorado, Denver | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Rtcp-Faces | Kisumu | Kenya |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37620855 | Derived | Scallon AJ, Hassan SA, Qian SR, Gao Y, Oyaro P, Brown E, Wagude J, Mukui I, Kinywa E, Oluoch F, Odhiambo F, Oyaro B, Kingwara L, Yongo N, Karauki E, Otieno L, John-Stewart GC, Abuogi LL, Patel RC. "I feel drug resistance testing allowed us to make an informed decision": qualitative insights on the role of HIV drug resistance mutation testing among children and pregnant women living with HIV in western Kenya. BMC Health Serv Res. 2023 Aug 24;23(1):908. doi: 10.1186/s12913-023-09804-x. | |
| 36528677 |
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De-identified individual participant data for all outcome measures will be made available after study completion
After primary outcomes results are published.
Contact PIs of the study and obtain institutional ethic review approvals.
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The study was conducted in Kisumu County, western Kenya, with the second-highest prevalence of pediatric HIV infections in Kenya. The study was implemented at five low-resource, high-HIV burden public sector facilities from March 2019 to December 2020. We chose the study facilities to leverage existing POC technologies, specifically the GeneXpert® platform.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. 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. |
| FG001 | Intervention | POC VL and targeted DRM testing. 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. 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. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Viral Suppression | Viral Load <1000 copies/mL at 12 months after enrollment | Posted | Number | participants | 12 months after enrollment |
|
The adverse events were reported from enrollment to approximately 12 months after enrollment for each participant.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hospitalization | Gastrointestinal disorders | Non-systematic Assessment | Malnutrition |
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First, it is possible we had sample biased towards higher levels of viral suppression (VS). Second, though our package of POC VL testing, DRM testing, and clinical decision support was only offered to intervention group, the same providers cared for participants in intervention and control groups. Third, VS was assessed on different schedules for intervention and control, the intervention group participants had a greater number of opportunities to act on their test results and detect viremia.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Rena C. Patel | University of Washington | 206-520-3800 | rcpatel@uw.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 2, 2022 | Nov 8, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 11, 2022 | Nov 8, 2022 | SAP_001.pdf |
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| OTHER |
Randomized control trial of two study arms
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Investigators and those conducting the analysis will be blinded to arm allocation
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| SOC VL testing | Diagnostic Test | 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. |
|
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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 |
| Qian SRW, Hassan SA, Scallon AJ, Oyaro P, Brown E, Wagude J, Mukui I, Kinywa E, Oluoch F, Odhiambo F, Oyaro B, Kingwara L, Yongo N, Karauki E, Gao J, Otieno L, John-Stewart GC, Abuogi LL, Patel RC. "After viral load testing, I get my results so I get to know which path my life is taking me": qualitative insights on routine centralized and point-of-care viral load testing in western Kenya from the Opt4Kids and Opt4Mamas studies. BMC Health Serv Res. 2022 Dec 17;22(1):1540. doi: 10.1186/s12913-022-08593-z. |
| 35987208 | Derived | 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. |
| 33195874 | Derived | 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. |
| Death |
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| Transferred out |
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| Terminated |
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| Withdrawal by Subject |
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| BG001 | Intervention | POC VL and targeted DRM testing. 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. |
| BG002 | Total | Total of all reporting groups |
| Participants |
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| Age, Continuous | Median | Inter-Quartile Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Virological suppression at enrollment | Viral load <1000 copier per mL at enrollment or most recent up to 2 years prior | Count of Participants | Participants |
|
Point-of-care (POC) viral load (VL) and targeted Drug resistance mutation (DRM) testing. POC VL and targeted DRM testing: POC VL 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 antiretroviral (ART) and when viremia (VL>1000 copies/mL) is detected. |
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| Secondary | 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. | Posted | Count of Participants | Participants | 12 months post enrollment |
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| Secondary | 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. | Of note, during the 6- and 9-month study visits, COVID-19 related restrictions in travel and routine care greatly affected our ability to obtain samples for VL testing leading to varying numbers analyzed per month. | Posted | Number | participants | Every 3 months within the 12 months study period |
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| Secondary | 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. | Posted | Median | Inter-Quartile Range | days | Every 3 months within the 12 months study period |
|
|
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| Secondary | 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. | Of 120 samples in the intervention group in which we requested a DRM test, 13 (11%) failed to amplify. We are not able to elucidate reasons why five of the samples in the Standard of Care group were selected for DRM testing or why three of the five requested DRM tests were not performed successfully. | Posted | Number | participants | 12 months post enrollment |
|
|
|
| 2 |
| 355 |
| 1 |
| 355 |
| 0 |
| 355 |
| EG001 | Intervention | POC VL and targeted DRM testing. 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. | 1 | 349 | 0 | 349 | 0 | 349 |
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| 3 months |
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| 6 months |
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| 9 months |
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| 12 months |
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| NNRTI |
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| Protease Inhibitor |
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| Any major DRM |
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| Major NRTI |
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| Major NNRTI |
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| Major protease Inhibitor |
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