Second-line Therapy

Study Overview
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Brief Summary
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This study will help identify which ARV candidates should be prioritized for pediatric use in resource-limited settings

Detailed Description
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Children in resource-limited settings are increasing experiencing treatment failure, as defined by virologic, immunologic, and/or clinical criteria. There are few studies of HIV resistance mutations in children failing first line NNRTI therapy in resource limited settings. The emergence of treatment failure and drug resistance in children on ART emphasizes the urgency for developing evidence-based second-line and salvage treatment strategies. Pediatric treatment is complicated by a number of factors, including having fewer numbers of ARVs approved by drug safety agencies and the lack of pediatric formulations. This further shortens the list of available second-line ARVs as compared to adults. Despite the growing number of children on second-line therapy worldwide, there are limited data on efficacy of second-line PI therapy in children after NRTI-NNRTI failure. There are currently no options for third-line/salvage regimens for children in resource-limited settings. New drugs and drug classes are approved for use in children by the US FDA but are not routinely available outside of high-income settings. Also, there are no data on the resistance patterns of children failing second-line therapy in resource-limited settings to guide clinical management and ARV procurement. Clinicians need evidence-based guidelines for how to manage children with treatment failure, and access to the drugs necessary to construct potent and durable third-line regimens. TASER-P is a longitudinal observational cohort study to monitor for treatment failure to second-line ART in Asian children.

Official Title
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TASER-Pediatrics: Prospective Monitoring of Second-line Antiretroviral Therapy Failure and Resistance in Children

Conditions
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Treatment Failure of Second-line ART in Asian HIV-infected Children

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age < 18 years old Have confirmed HIV infection Are being switched to or treated with second-line ART. Second-line ART is defined as the second regimen with a major antiretroviral class switch. For example, a switch from an NNRTI-based to a PI-based regimen or vice versa Caregivers give informed consent. Children will be asked to give assent if they know their HIV status and have reached the minimum age to give assent according to each site's institutional review board regulations Exclusion Criteria: Started mono- or dual- therapy as the first ART therapy Failing first-line triple nucleoside reverse transcriptase inhibitor regimen Are being switched to or treated with second-line ART without failure of first-line therapy (i.e., for toxicity) Caregiver +/- child (if asked to give assent) refuses to participate in this study Have not been enrolled in TApHOD

Ages Eligible for Study
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Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| second-line pediatric cohort<br>Asian HIV-positive children <18 years old who are receiving HIV care at one of the participating TREAT Asia Pediatric HIV Observational Database (TApHOD) sites that have been identified for TASER-P participation will be monitored for treatment failure of second-line ART | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| resistance | To monitor for resistance development and resistance patterns in children failing second-line ART over 72 weeks | week 72 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| virologic failure | To determine the frequency of virologic suppression defined as HIV-RNA <400 copies/ml over 72 weeks To determine the frequency of virologic failure as HIV RNA ≥1000 copies/ml over 72 weeks To evaluate predictors of virologic failure | week 72 | 
| drug resistance | To assess HIV drug resistance patterns by virtual phenotyping | week 72 | 
| ARV drug levels | To correlate ARV drug levels between plasma and hair samples To correlate hair ARV levels with virologic responses and measures of adherence | week 72 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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therapeutic drug monitoring (TDM), drug levels in blood and hair, longitudinal observational cohort study, multicenter, pediatrics, Asian, treatment failure, renal status, toxicities