Sustainable Adherence and Prevention of HIV Drug Resistance in Adolescents

NCT ID: NCT03928834

Last Updated: 2020-11-25

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: NA
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-31
• Study Completion Date: 2021-09-30

Brief Summary

The overall goal of this study is to determine if implementation of a package of interventions that includes DBS-based VL monitoring, coupled with an evidence-based intervention to improve ART adherence using cognitive-behavioral principles and genotyping for those with persistent viremia decreases 12-month virologic failure rates among HIV-infected adolescents compared with standard of care (SOC).

Detailed Description

In 2014, UNAIDS set ambitious goals to achieve 90% virologic suppression rates among individuals on antiretroviral therapy (ART). In Zimbabwe, this is an ambitious target, particularly among adolescents; less than 5% of human immunodeficiency virus (HIV)-infected individuals received HIV viral load (VL) testing in 2015, as reported by Ministry of Health and Child Care in Zimbabwe and treatment failure rates among adolescents range between 25-37% (Makadzange et al., 2015). Adolescents failing ART also have high rates of drug resistance. Scalable strategies to facilitate improved VL monitoring, adherence support, and genotyping for those with persistent viremia are urgently needed. The investigators have shown that dried blood spot (DBS) samples can be used for routine VL monitoring on existing technologies (Makadzange et al., 2017) They have also adapted an evidence-based, widely-used, cognitive behavioral therapy (CBT) adherence intervention (Life-Steps) for use in Zimbabwe and have identified a low-cost genotyping strategy that can facilitate detection of drug resistance mutations (DRMs) using already existing real-time polymerase chain reaction technology. The primary study objective is to determine if implementation of a package of care that includes DBS-based VL monitoring, coupled with an evidence-based intervention to improve ART adherence using cognitive-behavioral principles as well as genotyping for individuals with persistent viremia decreases 12-month virologic failure rates among HIV-infected adolescents compared with standard of care (SOC). The investigators hypothesize that the proposed package of care will result in a decrease in virologic failure rates among adolescents. They will also adapt and integrate Nzira Itsva for Adolescents (NI), a cultural adaptation of Life-Steps, into routine care as an adherence support intervention for HIV-infected adolescents, and implement a novel, low-cost genotyping assay using Pan-Degenerate Amplification and Adaptation (PANDAA) of viral ribonucleic acid (RNA) as a point mutation assay for the detection of drug resistance in parallel with Sanger sequencing. Process and cost data will be collected for subsequent cost-analysis. The proposed intervention will be a two-arm, cluster-randomized trial in Mashonaland West and Matabeleland North provinces of Zimbabwe. The units of randomization will be public and largely rural clinics within the provinces, with sites randomized to the intervention or to the SOC. The study is anticipated to show that the use of DBS in routine monitoring of adolescents is feasible, and to show that CBT, if incorporated into routine counselling activities, can complement VL monitoring and genotyping to reduce treatment failure rates and preserve therapeutic options for infected adolescents. The results of this study will have important implications in Zimbabwe and other low-income countries in sub-Saharan Africa with a large proportion of HIV-infected adolescents. The study will include young adolescents aged 10- <14years, as well as older adolescents aged 15-19 years and therefore provide data that will guide implementation of strategies for virologic success in the growing number of perinatally-infected children who are surviving on ART into adolescence, as well as for behaviorally-infected adolescents. The study will be performed within 44 clinics in Matabeleland North and Mashonaland West provinces, and will recruit 828 adolescents. A multidisciplinary consortium with the expertise to conduct this study has been assembled. The consortium includes public health practitioners, a biostatistician, basic scientists with extensive experience in virology and development of novel technologies, HIV clinicians with experience in implementation science, global mental health, and behavioral psychology experts. The consortium will work in partnership with the Ministry of Health (MOH) to implement this protocol and ensure its success.

Conditions

Medication Adherence; HIV Drug Resistance

Keywords

Adolescents; HIV drug resistance; Genotyping; Dried blood spots

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: HEALTH_SERVICES_RESEARCH
• Blinding Strategy: NONE

Study Groups

Adapted Nzira Itsva Intervention

Participants will be attending clinics that provide an enhanced adherence package to the adolescents consisting of viral load (VL) testing using DBS, including the Nzira Itsva(NI) intervention and low-cost genotyping and drug resistance monitoring

Group Type: EXPERIMENTAL

Adapted Nzira Itsva

Intervention Type: BEHAVIORAL

Adolescents will be provided an enhanced adherence package consisting of VL testing using DBS, including the NI intervention and low-cost genotyping and drug resistance monitoring. Participants receiving the intervention will have their first session after recruitment and enrollment, and will schedule up to 4 additional booster sessions at a time convenient for them spaced approximately 1 month apart. This may be modified after the formative assessment.

Standard of Care( SOC)

Participants will be attending clinics that provide the standard of care (SOC) VL testing and management to adolescents

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Adapted Nzira Itsva

Adolescents will be provided an enhanced adherence package consisting of VL testing using DBS, including the NI intervention and low-cost genotyping and drug resistance monitoring. Participants receiving the intervention will have their first session after recruitment and enrollment, and will schedule up to 4 additional booster sessions at a time convenient for them spaced approximately 1 month apart. This may be modified after the formative assessment.

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

1. HIV-positive adolescents aged 10-19 years who know their status

2. On ART for at least 6 months as per clinic records: the patient will have attended the clinic as shown in clinic records at least once since initiation AND will have re-filled their ART at least once since initiation as shown in clinic records..

3. Planning to stay in care at that facility for at least 12 months

Exclusion Criteria

1. Participant and/or caregiver unable to give consent and assent

2. Those participants who the healthcare worker considers to be too ill to participate

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

King's College London

OTHER

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: collaborator

University of Zimbabwe

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chiratidzo E NDHLOVU, MD

Role: PRINCIPAL_INVESTIGATOR

University of Zimbabwe

Locations

University of Zimbabwe

Harare, , Zimbabwe

Countries

Zimbabwe

Other Identifiers

GH002118-01

Identifier Type: -

Identifier Source: org_study_id