East Africa Point of Care Viral Load Study

The purpose of the project is to examine the feasibility, acceptability, and effectiveness of using point of care viral load (PoC VL) monitoring to improve viral load suppression among children and adolescents (age ≤19 years) living with HIV in Kenya, Rwanda, Tanzania and Uganda.

Main Study Aims:

i) To determine the effectiveness of PoC VL monitoring in improving viral suppression among children and youth living with HIV in East Africa.

ii) To evaluate feasibility and acceptability of using PoC VL monitoring among children and adolescents living with HIV in East Africa.

Objectives of Aim 1:

Primary objective i. To estimate the effect of PoC VL monitoring on viral load suppression among children and adolescents living with HIV in East Africa at 6 and 12 months of follow-up.

Secondary objectives i. To describe the effect of PoC VL monitoring on the proportion of children and adolescents living with HIV that experiences virological rebound after initial suppression within 6 and 12 months of follow-up.

ii. To describe the effect of PoC VL monitoring on time to initiation of intensive adherence counselling following virological failure among children and adolescents living with HIV.

iii. To estimate the effect of PoC VL monitoring on the proportion of children and adolescents living with HIV that experiences change of antiretroviral therapy (ART) regimen within 6 and 12 months of follow-up.

iv. To determine the effect of PoC VL monitoring on the proportion of children and adolescents living with HIV that is retained in care at 6 and 12 months.

Objectives of Aim 2 i. To assess the acceptability of the implementation and scale-up of PoC VL testing and monitoring from the perspective of children, adolescents and their caregivers.

ii. To assess the critical determinants that may affect the implementation of PoC VL testing and monitoring from the perspective of healthcare workers and policy makers.

iii. To assess potential barriers and facilitators to implementation and scale-up of PoC VL testing and monitoring among children and adolescents living with HIV.

iv. To assess the incremental cost-effectiveness of PoC VL from a modified societal perspective using established models, with data collected alongside the implementation of the intervention combined with data estimated based on existing studies.

Design: A cluster randomized controlled trial with 10 intervention clusters and 10 control clusters.

Study Sites: Twenty (20) health facilities spread across 4 countries as follows: Uganda (6), Kenya (4), Tanzania (6), and Rwanda (4).

Population: The study will be conducted among three population sub-groups

1. Study population 1: children and adolescents (≤19 years) living with HIV in participating countries in East Africa.
2. Study population 2: Care givers/ guardians and treatment supporters of children and adolescents living with HIV in participating countries in East Africa
3. Study population 3: Health care workers attending to children and adolescents living with HIV, and policy makers.

Study Intervention: PoC VL monitoring using the Abbott platform Control: Standard-of-care / centralized HIV VL monitoring

Duration: The whole project will take 48 months including 24 months of data collection. Each participant will be followed up for a minimum of 12 months and maximum 24 months.

Sample size The study will enroll 1440 children and youth (0-24years); with 720 in 10 intervention clusters and 720 in 10 control clusters (72 participants per cluster). The effect of the intervention and 95% confidence intervals (CIs) will be estimated using cluster-level summary methods and a power of 80%. To ensure equal distribution of the participants across the ages, we aim to split the enrollment proportionally according to the cluster sizes into three age groups of (0-5 years, 6-12 years and 13-19 years).

Statistical Analysis Aim 1

To investigate the effect of the intervention on viral suppression our analysis will be carried out at the cluster level as follows:

* Reduce clusters to independent observations and provide summary statistics by comparing those in the intervention arm to those in the non-intervention arm.
* Use fixed effects regression to take into account unobserved time-invariant heterogeneity and the treatment effects across the clusters
* Analyze the main outcome (viral suppression) using time to event comparison of the two arms from enrollment to failure or completion of the follow-up time (2 years).

Mixed method Analysis Aim 2 Acceptability and feasibility will be investigated using a combined qualitative and quantitative approach, consisting of thematic content analyses of observations, in-depth interviews and focus group discussions, triangulated and generalized with descriptive statistics of survey data. As part of the feasibility study, the impact of a range of values in sensitivity analyses using each of the respective sites' 2020 per capita Gross Domestic Product (GDP) as a benchmark cost-effectiveness threshold will be evaluated to be able to estimate the incremental cost-effectiveness of the POC VL compared to the standard of care. Quality adjusted life years (QALYS) will be calculated based on weights derived from the Global Burden of Disease.

Eligibility Criteria:
Inclusion Criteria:

* Age 6 months - 19 years
* Documented evidence of HIV infection
* Receiving ART for treatment of HIV infection for at least 6 months.
* Has had a detectable VL of \>1000 copies/ml in the last 6 months.
* Guardian, parent or legal representative able and willing to give voluntary consent and sign/mark an informed consent document.
* Willing and able to comply with protocol requirements/study procedures.

Exclusion Criteria:

* Any medical conditions that require pausing of ART for more than three months.
* Potential participant already enrolled in another study which may interfere with the study outcome or participation as per investigator's judgement.
* Child or adolescent already enrolled and completed follow up in the current study.
* Any medical or other condition in the potential participant or their parent/ guardian that precludes provision of informed consent/ assent or that may hinder achieving study objectives as per investigator's judgement.