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

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

Interventions

OTHER

modified directly administered anti-retroviral therapy (mDAART)

As described before

Sponsors & Collaborators

• Fogarty International Center of the National Institute of Health

  collaborator NIH

• National Institute of Allergy and Infectious Diseases (NIAID)

  collaborator NIH

• University of Zimbabwe

  lead OTHER

Principal Investigators

• Tariro D Chawana, Doctor · University of Zimbabwe

• Kusum Nathoo, Professor · University of Zimbabwe

• Charles FB Nhachi, Professor · University of Zimbabwe

Study Design

Allocation

RANDOMIZED

Purpose

SUPPORTIVE_CARE

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

10 Years

Max Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2014-02-28

Primary Completion

2017-01-31

Completion

2017-01-31

Countries

• Zimbabwe

Study Locations