Etiology of Treatment Failure in HIV Positive Children and Adolescents on Boosted Protease Inhibitor-based Regimens

NCT02689895 | Completed

• 4 other identifiers: ATF study2U2RTW0073672R01AI0984721D43TW009539
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

Brief Summary

Highly active antiretroviral therapy (HAART) transformed a once fatal condition into a chronic, manageable condition. However, it is estimated that 20-40% of patients on 2nd line treatment (2 nucleotide reverse transcriptase inhibitors \[NRTIs\] and a boosted protease inhibitor \[PI\]) are failing treatment. Figures are thought to be higher in children and adolescents. The reason why patients are failing 2nd line treatment is not exactly known. Failure has been previously attributed to poor adherence. However, some literature shows that some patients on boosted PIs achieve and maintain viral suppression despite suboptimal adherence (adherence of 80- 95%). Viral factors, like drug resistance, are also implicated in treatment failure. However, boosted PIs have high genetic barrier to clinically significant mutations. Therefore, a virus would have to harbour multiple PI mutations for the virus to have reduced susceptibility to boosted PI regimens. Pharmacological factors such as suboptimal dosing, impaired absorption and drug interactions may also be responsible for treatment failure. If sub-optimal adherence is the reason why children are failing 2nd line treatment, then restoring optimal adherence should result in viral suppression, failure of which might mean that other causes are contributing to failure. If resistance is the cause of treatment failure, then this study will provide evidence for advocating for resistance testing and the use of 3rd line antiretroviral drugs. If children with adequate adherence demonstrate inadequate drug levels in their plasma, then this study will provide evidence to advocate for studies to examine reasons for inadequate drug exposure amongst HIV-infected children. These studies are paramount to optimizing dosing algorithms in this population. This proposed study will help elucidate reasons for treatment failure in HIV-infected children on second line treatment with the aim of ultimately optimizing antiretroviral treatment strategies for this important group.

Conditions

HIV

Keywords

adolescents; second line treatment failure; adherence; drug resistance

Outcome Measures

Primary Outcomes (1)

• Number of Participants with treatment success described as viral load below 1 000 copies/ml at the end of follow-up.

  Participants with viral load \>=1 000 copies/ml will be described as treatment failure and proceed to have genotyping for drug resistance.

  3 months

Study Arms (2)

Intervention

OTHER

Research assistants visit participants at home, and send SMS texts on scheduled days for 3 months to encourage adherence to ART. Pill charts, visit charts and text charts are completed. this is called modified directly administered anti-retroviral therapy (mDAART). In addition to the intervention, participants receive standard care at their usual clinic which comprises 3 monthly doctor reviews and adherence counseling at each review visit.

Other: modified directly administered anti-retroviral therapy (mDAART)

Control

NO INTERVENTION

Participants get usual care at their clinic, which comprises 3 monthly doctor review visits and adherence counseling at each visit.

Interventions

modified directly administered anti-retroviral therapy (mDAART) OTHER

As described before

Intervention

Eligibility Criteria

• Age: 10 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Parents/guardian willing to consent
• Child willing to provide assent
• Documented HIV positive antibody or antigen test
• Child knows their HIV status
• Aged between 6 and 18 years (that is, from the day of their 6th birthday up to the eve of their 18th birthday)
• Registered at Harare hospital paediatric opportunistic infections clinic
• On second line treatment (ATV/r based)
• Have taken the above named second line treatment for at least 6 complete, consecutive months
• Has virological and immunological treatment failure as defined by WHO 2012 criteria

You may not qualify if:

• Patients registered at other health centres who have been referred for specialist care at Harare hospital paediatric opportunistic infections clinic
• On ATV/r as first line treatment
• Patients who do not want to be followed up at home.
• On anti-tuberculosis (TB) treatment

Sponsors & Collaborators

• University of Zimbabwe: lead
• Fogarty International Center of the National Institute of Health: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (2)

Beatrice Road Infectious Disease Hospital

Harare, +263, Zimbabwe

Location

Harare Central Hospital

Harare, +263, Zimbabwe

Location

Study Officials

• Tariro D Chawana, Doctor

  University of Zimbabwe

  PRINCIPAL INVESTIGATOR

• Kusum Nathoo, Professor

  University of Zimbabwe

  PRINCIPAL INVESTIGATOR

• Charles FB Nhachi, Professor

  University of Zimbabwe

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr

Study Record Dates

• First Submitted: February 13, 2016
• First Posted: February 24, 2016
• Study Start: February 1, 2014
• Primary Completion: January 1, 2017
• Study Completion: January 31, 2017
• Last Updated: February 13, 2018

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

ZI (2)