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Pediatric HIV Clinical PharmacologyProgram Development in Thailand

Tim R. CresseyResearch Associate, Harvard School of Public Health, USA

PHPT-IRD, Chiang Mai University, Thailand

4th Annual Workshop on Global HIV Clinical Pharmacology Capacity Building and Implementation Research

July 1st, 2013

7th IAS Conference on HIV Pathogenesis, Treatment and PreventionKuala Lumpur, Malaysia

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Chiang Mai • PHPT: a research group created in 1996 in Chiang Mai, the epicenter of the HIV epidemics in Thailand at that time

• Main objectives are to determine strategies for preventing mother to child transmission of HIV, and HIV/AIDS treatment and care that can be integrated in the existing health care system.

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Programs for HIV Prevention and Treatment www.phpt.org

(previously Perinatal HIV Prevention Trials)

A collaborative initiative including researchers from:

• Ministry of Public Health, Chiang Mai and Mahidol Universities in Thailand• Harvard School of Public Health and School of Medicine, Boston, MA, USA• Institut de Recherche pour le Développement, Institut National d’Etudes

Démographiques and INSERM; Lyon 2 & Paris 7 University, France

• International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT)• Pediatric European Network for the Treatment of AIDS (PENTA)• RIHES, HIV-NAT, CDC, Mahidol University, Chulalongkorn University in Thailand;• Harvard, Seattle, Tours, Paris, Lyon, Liverpool Universities

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Network of 50 Public hospitals

PHPT Network

• More than 120 physicians, 250 nurses, counselors, laboratory technicians, pharmacists, in a network of hospitals

• Laboratory dedicated to HIV Research at Chiang Mai University

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PHPT-AMS Laboratory• Established in 2001 at the Faculty of Associated Medical

Sciences, Chiang Mai University‒ HIV RNA Viral Load, HIV Genotyping, HIV DNA-PCR, Antiretroviral drug

level measurement

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Particular research focus on the pharmacokinetics of antiretroviral drugs

in pregnant women and children

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PHPT-AMS Pharmacology Laboratory

• 2005: Secured first HPLC Machine (Agilent LC1100)

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ARV Assay Development• Many high performance liquid chromatography assays (HPLC)

with UV detection for single and multiple ARV drugs are available• A few HPLC assays can over the majority of ARV drugs

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Laboratory Quality Assurance System

[Work Instructions (WI): documents describing test procedures for ISO15189 Accreditation]

Standard Operating Procedures (SOPs)

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Quality Control Samples

External Quality Control (EQC) Programs

1. External Quality Controls sample from Clinical Pharmacology Quality Assurance and Quality Control, USA (CPQA) will be performed twice yearly.

2. To monitor inter-day assay variability QC samples provided from ASQUALAB (France, http://www.asqualab.com/) are included in each run.

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Internal Monitoring of QC samples

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Laboratory Accreditation• PHPT Laboratory was first accredited by the Thai

Medical Technology Council in 2005

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PHPT Pharmacology Laboratory: 2008

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2011

2009

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ISO 15189: Medical Laboratory Accreditation

• ISO 15189:2012 is for use by medical laboratories in developing their quality management systems and assessing their own competence, and for use by accreditation bodies in confirming or recognizing the competence of medical laboratories.

• PHPT laboratory was ISO15189 accredited by Bureau of Laboratory Quality Standards, Thai MoPH, in 2011

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Supporting PK Research Studies

Lamivudine

Nevirapine

Efavirenz

Lopinavir/r

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Therapeutic Drug Monitoring (TDM)(within the PHPT-GFATM program)

Since 2005• Samples: 9,300 tests performed

Reasons• Drug toxicity• PI dosing in Children• Dual-Boosted PIs• Non-ARV drug-drug interactions

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Staff Training at CPQA, Buffalo, USA• Assay Validation• Quality Control, Quality Assurance, Competency, Laboratory Self-Assessment • Quality Data Management • New Technologies: UPLC and Mass Spectrometry

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2013

Agilent 6460 LC-MS-MS

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Future Technology Transfers

• Establish capacity to measure intracellular antiretrovirals concentrations

• Establish capacity to measure antiretrovirals on dried blood (or plasma) spots (DBS) or hair samples

• Continue the development of Laboratory Quality Assurance System (GLP, IS017025)

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Acknowledgments

Support• Ministry of Public Health, Thailand

• Thailand International Development Cooperation Agency (TICA)

• NICHD, NIAID, USA

• Institut de Recherche pour le Développement (IRD), France

• Global Fund to fight AIDS, Tuberculosis and Malaria (THA-102-G01-H-00)

This satellite was sponsored by the UB-UZ AIDS International Training Research program funded by the Fogarty International Center.

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Thank You