1. Programs for HIV Prevention and TreatmentIRD UMI 174 Pediatric HIV Clinical Pharmacology Program Development in Thailand Tim R. Cressey Research Associate, Harvard School of Public Health, USA PHPT-IRD, Chiang Mai University, Thailand 4 th Annual Workshop on Global HIV Clinical Pharmacology Capacity Building and Implementation Research July 1 st, 2013 7 th IAS Conference on HIV Pathogenesis, Treatment and Prevention Kuala Lumpur, Malaysia

2. Programs for HIV Prevention and TreatmentIRD UMI 174 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.

3. Programs for HIV Prevention and TreatmentIRD UMI 174 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

4. Programs for HIV Prevention and TreatmentIRD UMI 174 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

5. Programs for HIV Prevention and TreatmentIRD UMI 174 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

6. Programs for HIV Prevention and TreatmentIRD UMI 174 Particular research focus on the pharmacokinetics of antiretroviral drugs in pregnant women and children

7. Programs for HIV Prevention and TreatmentIRD UMI 174 PHPT-AMS Pharmacology Laboratory 2005: Secured first HPLC Machine (Agilent LC1100)

8. Programs for HIV Prevention and TreatmentIRD UMI 174 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

9. Programs for HIV Prevention and TreatmentIRD UMI 174 9 Laboratory Quality Assurance System [Work Instructions (WI): documents describing test procedures for ISO15189 Accreditation] Standard Operating Procedures (SOPs)

10. Programs for HIV Prevention and TreatmentIRD UMI 174 10 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.

11. Programs for HIV Prevention and TreatmentIRD UMI 174 Internal Monitoring of QC samples 11

12. Programs for HIV Prevention and TreatmentIRD UMI 174 Laboratory Accreditation PHPT Laboratory was first accredited by the Thai Medical Technology Council in 2005

13. Programs for HIV Prevention and TreatmentIRD UMI 174 PHPT Pharmacology Laboratory: 2008

14. Programs for HIV Prevention and TreatmentIRD UMI 174 2011 2009

15. Programs for HIV Prevention and TreatmentIRD UMI 174 15 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

16. Programs for HIV Prevention and TreatmentIRD UMI 174 Supporting PK Research Studies Lamivudine Nevirapine Efavirenz Lopinavir/r

17. Programs for HIV Prevention and TreatmentIRD UMI 174 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

18. Programs for HIV Prevention and TreatmentIRD UMI 174 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

19. Programs for HIV Prevention and TreatmentIRD UMI 174 2013 Agilent 6460 LC-MS-MS

20. Programs for HIV Prevention and TreatmentIRD UMI 174 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)

21. Programs for HIV Prevention and TreatmentIRD UMI 174 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.

22. Programs for HIV Prevention and TreatmentIRD UMI 174 22 Thank You