Clinical trial NCT03820323: Optimizing Viral Load Suppression in Kenyan Children on Antiretroviral Therapy
Official title: Optimizing Viral Load Suppression in Kenyan Children on Antiretroviral Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic HIV Infection
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
name: Kenya Medical Research Institute
name: University of Colorado, Denver
name: University of Washington
First posted: 2019-01-29
Enrollment: 704
Sex: ALL
Minimum age (years): 1
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized control trial of two study arms
Primary purpose: DIAGNOSTIC

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.

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.

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

Primary outcomes:
measure: Number of Participants With Viral Suppression
timeFrame: 12 months after enrollment
Secondary outcomes:
measure: Virological Suppression at 12 Months Among Children Newly Initiating ART or Initially Virologically Unsuppressed
timeFrame: 12 months post enrollment
measure: Number of Participants Who Underwent POC VL Testing
timeFrame: Every 3 months within the 12 months study period
measure: Turn-around Time for the VL Testing Results
timeFrame: Every 3 months within the 12 months study period
measure: Number of Children With Any or Major Drug Resistance Mutations (DRMs)
timeFrame: 12 months post enrollment
Other outcomes:
Locations:
city: Kisumu
country: Kenya
facility: Rtcp-Faces
Study officials:
affiliation: University of Alabama at Birmingham
name: Rena Patel, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Colorado, Denver
name: Lisa L Abuogi, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.