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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02689895
Recruitment Status : Completed
First Posted : February 24, 2016
Last Update Posted : February 13, 2018
Sponsor:
Collaborators:
John E. Fogarty International Center (FIC)
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
Tariro Chawana, University of Zimbabwe

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.


Condition or disease Intervention/treatment Phase
HIV Other: modified directly administered anti-retroviral therapy (mDAART) Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: Etiology of Treatment Failure in HIV Positive Children and Adolescents on Boosted Protease Inhibitor-based Regimens
Actual Study Start Date : February 2014
Actual Primary Completion Date : January 2017
Actual Study Completion Date : January 31, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Intervention
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)
As described before

No Intervention: Control
Participants get usual care at their clinic, which comprises 3 monthly doctor review visits and adherence counseling at each visit.



Primary Outcome Measures :
  1. Number of Participants with treatment success described as viral load below 1 000 copies/ml at the end of follow-up. [ Time Frame: 3 months ]
    Participants with viral load >=1 000 copies/ml will be described as treatment failure and proceed to have genotyping for drug resistance.



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Ages Eligible for Study:   10 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02689895


Locations
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Zimbabwe
Beatrice Road Infectious Disease Hospital
Harare, Zimbabwe, +263
Harare Central Hospital
Harare, Zimbabwe, +263
Sponsors and Collaborators
University of Zimbabwe
John E. Fogarty International Center (FIC)
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
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Principal Investigator: Tariro D Chawana, Doctor University of Zimbabwe
Principal Investigator: Kusum Nathoo, Professor University of Zimbabwe
Principal Investigator: Charles FB Nhachi, Professor University of Zimbabwe

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Responsible Party: Tariro Chawana, Dr, University of Zimbabwe
ClinicalTrials.gov Identifier: NCT02689895    
Other Study ID Numbers: ATF study
2U2RTW007367 ( U.S. NIH Grant/Contract )
2R01AI098472 ( U.S. NIH Grant/Contract )
1D43TW009539 ( U.S. NIH Grant/Contract )
First Posted: February 24, 2016    Key Record Dates
Last Update Posted: February 13, 2018
Last Verified: April 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Tariro Chawana, University of Zimbabwe:
adolescents
second line treatment failure
adherence
drug resistance
Additional relevant MeSH terms:
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HIV Seropositivity
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
HIV Protease Inhibitors
Anti-Retroviral Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Antiviral Agents
Anti-Infective Agents