Clinical trial NCT03986099: Community Based Antiretroviral Therapy (CBART) Among Children on Chronic ART
Official title: Community Based Virus Load Differentiated Care in Rural Africa
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: ART
HIV I Infection
Keywords: Children and adolescents
HIV therapy
Virologic suppression
Zimbabwe
Rural
GeneXpert
Point of care
SAMBA
Lead sponsor: Biomedical Research and Training Institute, Zimbabwe
Sponsor class: OTHER
Collaborators: name: Gilead Sciences
First posted: 2019-06-14
Enrollment: 451
Sex: ALL
Minimum age (years): 2
Maximum age (years): 26
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Patients assigned to either point of care (POC) or standard of care (SOC)
Primary purpose: DIAGNOSTIC

Brief 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.

Eligibility criteria: Inclusion Criteria:

- HIV positive children and adolescents on ART

Exclusion Criteria:

* Unable to consent
* Less than one year on ART

Primary outcomes:
measure: Viral load suppression
timeFrame: 48 weeks
Secondary outcomes:
measure: Number of participants with confirmed virology failure who switched regimens
timeFrame: 96 weeks
measure: Drug resistance mutations
timeFrame: 96 weeks
Other outcomes:
Locations:
city: Karoi
country: Zimbabwe
facility: Chidamoyo Christian Hospital
state: Mashonaland West
Study officials:
affiliation: Biomedical Research and Training Institute
name: Shungu Munyati, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kouamou V, Machekano R, Mapangisana T, Maposhere C, Munyati S, Mutsvangwa J, Shamu T, McCarty K, Katzenstein D, Manasa J. Tenofovir, Lamivudine, and Dolutegravir Among Rural Adolescents in Zimbabwe: A Cautionary Tale. AIDS Res Hum Retroviruses. 2022 Oct;38(10):774-778. doi: 10.1089/AID.2021.0140. Epub 2022 Sep 7.