Second-line Therapy (TASER-P)

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

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

Study Overview

• Status: Completed
• Conditions: Treatment Failure of Second-line ART in Asian HIV-infected Children

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 300

Contacts and Locations

Study Locations

• Indonesia
  • Jakarta, Indonesia, 10430
    • Mangunkusumo General Hospital
• Malaysia
  • Kuala Lumpur, Malaysia, 50586
    • Hospital Kuala Lumpur
• Thailand
  • Bangkok, Thailand, 10700
    • Siriraj Hospital
  • Bangkok, Thailand, 10330
    • HIV-NAT
  • Chiang Mai, Thailand, 50200
    • Research Institute for Health Sciences
  • Khon Kaen, Thailand, 40002
    • Srinagarind Hospital, Khon Kaen University
• Vietnam
  • Ho Chi Minh City, Vietnam
    • Children's Hospital Number 1
  • Ho Chi Minh City, Vietnam
    • Children's Hospital Number 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

HIV-positive children <18 years old who are have switched to or treated with second-line ART at one of the participating TREAT Asia Pediatric HIV Observational Database (TApHOD) sites.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
second-line pediatric cohort; 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?

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

Collaborators and Investigators

• Sponsor: The HIV Netherlands Australia Thailand Research Collaboration
• Collaborators: University of California, San Francisco; amfAR, The Foundation for AIDS Research; Mahidol University; Dr Cipto Mangunkusumo General Hospital; Chiang Mai University; Pediatric Institute, Hospital Kuala Lumpur; Srinagarind Hospital, Khon Kaen University; Children's Hospital Number 1, Ho Chi Minh City, Vietnam; Children's Hospital Number 2, Ho Chi Minh City, Vietnam; The Kirby Institute for Infection and Immunity in Society
• Investigators: Principal Investigator: Nia Kurniati, MD, Dr Cipto Mangunkusumo General Hospital; Principal Investigator: Kamarul Razali, MD, Kuala Lumpur General Hospital; Principal Investigator: Tavitiya Sudjaritruk, MD, Research Institute for Health Sciences, Chiang Mai University; Principal Investigator: Pope Kosalaraksa, MD, Srinagarind Hospital, Khon Kaen Hospital; Principal Investigator: Kulkanya Chokephaibulkit, MD, Siriraj Hospital; Principal Investigator: Truong Huu Khanh, MD, Children's Hospital Number 1; Principal Investigator: Do Chau Viet, MD, Children's Hospital Number 2; Principal Investigator: Annette Sohn, MD, TREAT Asia

Publications and helpful links

Helpful Links

• HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)'s website

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: February 7, 2013
• First Submitted That Met QC Criteria: February 8, 2013
• First Posted (Estimate): February 11, 2013

Study Record Updates

• Last Update Posted (Estimate): May 11, 2016
• Last Update Submitted That Met QC Criteria: May 9, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: pediatrics; multicenter; treatment failure; Asian; longitudinal observational cohort study; renal status; toxicities; therapeutic drug monitoring (TDM); drug levels in blood and hair
• Other Study ID Numbers: HIV-NAT 149