Clinical trial NCT01788891: Second-line Therapy
Official title: TASER-Pediatrics: Prospective Monitoring of Second-line Antiretroviral Therapy Failure and Resistance in Children
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Treatment Failure of Second-line ART in Asian HIV-infected Children
Keywords: longitudinal observational cohort study
multicenter
pediatrics
Asian
treatment failure
renal status
toxicities
therapeutic drug monitoring (TDM)
drug levels in blood and hair
Lead sponsor: The HIV Netherlands Australia Thailand Research Collaboration
Sponsor class: OTHER
Collaborators: name: amfAR, The Foundation for AIDS Research
name: Dr Cipto Mangunkusumo General Hospital
name: Pediatric Institute, Hospital Kuala Lumpur
name: Chiang Mai University
name: Srinagarind Hospital, Khon Kaen University
name: Mahidol University
name: Children's Hospital Number 1, Ho Chi Minh City, Vietnam
name: Number 2 Children's Hospital, Ho Chi Minh City
name: Kirby Institute
name: University of California, San Francisco
First posted: 2013-02-11
Enrollment: 300
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: resistance
timeFrame: week 72
Secondary outcomes:
measure: virologic failure
timeFrame: week 72
measure: drug resistance
timeFrame: week 72
measure: ARV drug levels
timeFrame: week 72
Other outcomes:
Locations:
city: Jakarta
country: Indonesia
facility: Mangunkusumo General Hospital
city: Kuala Lumpur
country: Malaysia
facility: Hospital Kuala Lumpur
city: Bangkok
country: Thailand
facility: HIV-NAT
city: Bangkok
country: Thailand
facility: Siriraj Hospital
city: Chiang Mai
country: Thailand
facility: Research Institute for Health Sciences
city: Khon Kaen
country: Thailand
facility: Srinagarind Hospital, Khon Kaen University
city: Ho Chi Minh City
country: Vietnam
facility: Children's Hospital Number 1
city: Ho Chi Minh City
country: Vietnam
facility: Children's Hospital Number 2
Study officials:
affiliation: Dr Cipto Mangunkusumo General Hospital
name: Nia Kurniati, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Kuala Lumpur General Hospital
name: Kamarul Razali, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Research Institute for Health Sciences, Chiang Mai University
name: Tavitiya Sudjaritruk, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Srinagarind Hospital, Khon Kaen Hospital
name: Pope Kosalaraksa, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Siriraj Hospital
name: Kulkanya Chokephaibulkit, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital Number 1
name: Truong Huu Khanh, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital Number 2
name: Do Chau Viet, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The HIV Netherlands Australia Thailand Research Collaboration
name: Jintanat Ananworanich, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: TREAT Asia
name: Annette Sohn, MD
role: PRINCIPAL_INVESTIGATOR
References: