Community Based Antiretroviral Therapy (CBART) Among Children on Chronic ART
Condition: ART; HIV I Infection
Study type: Interventional

Summary: 
      A randomized, open label trial of two strategies for Virus Load Differentiated Care (VLDC)
      monitoring of virologic outcome in a rural community based treatment program in Zimbabwe.
    

Detailed description: 
      This is an open label randomized trial among HIV infected children and adolescents and young
      adults receiving ART at 8 treatment outreach sites near their homes provided by Chidamoyo
      Mission Hospital. The investigators will implement virus load (VL) testing at "near point of
      care" using either the GeneXpert Quant or the SAMBA to evaluate the safety, clinical and
      virologic outcomes of near POC monitoring of virus load at the Chidamoyo Christian Hospital
      in Mashonaland West Zimbabwe.

      The investigators hypothesize that our proposed package of care will result in a decrease in
      virologic failure, increase virologic suppression and prevent drug resistance in this key
      population in a rural ART treatment program. Process and cost data will be collected for
      subsequent cost-analysis.

      HIV infected children and adolescents on ART will be randomized (1:1) to either SOC (300) or
      a near POC VLDC monitoring. SOC VL is performed by Roche COBAS at the Provincial Hospital
      Chinhoyi and the results returned to the hospital within 4 weeks. Those randomized to near
      POC will be tested with the Cepheid GeneXpert assay and results are available within 3 days.
      Follow-up repeat testing for HIV RNA > 1,000 copies/ml is offered using the same virologic
      monitoring system at the next drug/clinic visit within 3 months.

      The hypothesis is that viral load monitoring and potentially genotyping to sustain
      suppression to < 1,000 copies/ml will reduce treatment failure to < 15%. Secondary endpoints
      include the rate of drug switching and the evaluation and prevention of drug resistance. The
      study will enroll up to 600 children (3 -10) years and adolescents (11-21) years, providing
      data that will guide strategies for management of children and adolescents who are surviving
      on ART.

      Primary Objective: To determine if implementation of point of care virus load differentiated
      care (POC virus load), targeted genotyping and mHealth tools will result in improved
      virologic suppression among children and adolescents (<21years) on ART.

      Sample size: The primary study endpoint is viral load suppression at 48 weeks among PLWHA <
      21 years old, using VLDC implemented as near POC compared to SOC semi- annual virus load
      testing. The investigators will enroll young PLWHA from eight communities and the Chidamoyo
      Hospital Clinic as a rolling prospective cohort. The investigators hypothesize that an
      intervention package of digitized data, local immediate POC Virus load and genotype will
      result in > 90% virologic suppression after 1 year. The estimated minimum sample size to
      detect at least a 15% increase in virologic suppression with 90% power, at significance level
      α=0.05 assuming 10% loss to follow up rate (LTFU) rate is 356 PLWHA on ART.

      Secondary endpoints:

        1. rate of switching from 1st to 2nd line.

        2. frequency of Drug Resistance Mutations (DRM) among 1st and 2nd line virologic failures.

        3. the frequency of Hepatitis B virus infection (HBSag).

      In collaboration with Ben Gurion University Global Health, the investigators will perform an
      ethnographic survey over the course of the primary study. The objective is to develop
      formative research to understand the individual and community variation in suppression rate
      and drug switching including differences in virologic failure and adherence by age, gender,
      rural outreach site, orphan-hood/caregiver and socio-economic status.
    

Intervention name(s): Monitoring virus load
Intervention type(s): Diagnostic Test
Intervention description(s): Near point of care
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Intervention model description: Patients assigned to either point of care (POC) or standard of care (SOC)
Masking: Single (Participant)
Primary purpose: Diagnostic
Keywords: Children and adolescents; HIV therapy; Virologic suppression; Zimbabwe; Rural; GeneXpert; Point of care; SAMBA