Page 1

CONTENTS

5 7 8 9

Foreword Messsage from the Co-directors HIV-NAT Clinical Trials Network Collaborations

11 14 16 18 19 21 23 23 24 25

OVERVIEW OF HIV-NAT STUDIES Pharmacokinetic & Pharmacogenomic Studies Clinical Research Programs in Co-Viral & Viral Infections Clinical Research Programs IN CO-TUBERCULOSis IINFECTIONS LONG TERM COHORT ANALYSIS STRATEGY STUDIES EXPANDED ACCESS PROGRAMS NEW DRUG DEVELOPMENT VACCINE RESEARCH PROGRAMS PEDIATRIC AND YOUTH RESEARCH PROGRAMS

29 32

PUBLICATIONS & WRITINGS PRESENTATIONS AT CONFERENCES AND MEETINGS

36 38

HIV-NAT RESEARCH LABORATORY THE VACCINE & CELLULAR IMMUNOLOGY LABORATORY

41

EDUCATION & DEVELOPMENT PROGRAM

44

The Bangkok International Symposium on HIV Medicine

45

HIV-NAT PERSONNEL

51

PARTNERSHIPS

60

Community Outreach Programs

63 64 65

International Advisory board acknowledgments sponsors

3


4


FOREWoRD

As Secretary General of the Thai Red Cross Society and Chairman of the hiv-nat International Advisory Board, I am pleased to introduce the 13th hiv-nat Annual Report. Phan Wannamethee Secretary General Thai Red Cross Society

This year, a total of sixty two studies were conducted. Impressively, there are eight strategic studies that will influence current hiv treatment guidelines as well as seven different long-term cohorts and fourteen pediatric studies. A new chapter in hiv research will unfold during 2010 with the addition of new doctors and study coordinators, venturing into other fields such as sexually transmitted diseases, other viral infections, prevention and psycho-social domains. For example, the start study, similar to the predict study, will examine the optimum timing of the initiation of art in adults. Coinciding with the h1n1 pandemic, hivnat, in collaboration with Chulalongkorn and Srinakarind (Khon Kaen) Hospitals will be conducting studies to assess the clinical characteristics of this influenza virus in Thai populations. Another study, hiv-star, will provide information on second-line therapy in adults where as third-line studies in children are in the pipeline. The past year saw the much anticipated publication of results of the Thai vaccine study. The results demonstrated that the vaccine was well-tolerated and had a modest effect in preventing hiv infection. While these findings represent an important step forward in hiv vaccine research, they underscore the critical need to continue research into new antiretroviral medicines and strategies to optimize the use of currently available medicines. hiv-nat continues to contribute to the international research effort through collaborative efforts with its partners both in Thailand and abroad. These collaborations have played a vital role in bringing to Thailand new antiretroviral classes and new generation antiretroviral drugs over the past year. We still face many challenges, including the management of non-aids illnesses as people are living longer with antiretroviral therapy and an explosion of hiv in adolescents and msm populations. Current hiv guidelines need to be revised and hopefully our studies will be able to provide evidence-based results that will impact the national program. Phan Wannamethee

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6


A MESSAGE FROM OUR CO-DIRECTORS

7

Welcome to the new look hiv-nat annual report. In addition to a fresh appearance and a much stronger affiliation with the Faculty of Medicine, Chulalongkorn University, the 13th annual report highlights key outcomes during 2009 in hiv-nat’s core research areas of pharmacokinetics, co-infections, new drug development, cohort and strategic studies. As the World Health Organization updates the guidelines for anti-retroviral therapy in adults and adolescent, two hiv-nat co-infection studies are included in the evidence base for the new recommendations. In deciding to recommend that all people with hiv and chronic hepatitis b should receive tenofovir and lamivudine/ emtricitabine (drugs active against both hiv and hepatitis b) just one randomized clinical trial, published in the journal Hepatology, was cited. This trial was conducted at hiv-nat in collaboration with our partners at nchecr. In the field of hiv-tb co-infection, another study of hiv-nat’s Dr Anchalee Avihingsanon was cited in support of the recommend-ation to use efavirenz in the presence of rifampicincontaining tb therapy. Typically, it takes seven to ten years to bring a new antiretroviral from the pre-clinical stage to the market. hiv-nat has worked with its pharmaceutical partners on the phase three development of a new generation protease inhibitor, darunavir, which was licensed in Thailand during 2009. As part of combination salvage therapy, it is bringing new hope to people living with hiv who have failed first and second line therapy. This new therapeutic option has also reached those in need in neighboring countries, with people traveling to hiv-nat to access salvage therapy not available in their countries.

1

2

3

1 Praphan Phanuphak 2 David Cooper 3 Joep Lange


HIV-NAT CLINICAL TRIaLS NETWORK

8

CHIANG RAI • CHIANG RAI REGIONAL HOSPITAL

CHIANG MAI • NAKORNPING HOSPITAL • SANPATONG HOSPITAL

khon kaen • SrinagarinD Hospital • KHON KAEN UNIVERSITY

BANGKOK • HIV-NAT – TRCARC • CHULALONGKORN HOSPITAL • SIRIRAJ HOSPITAL MAHIDOL UNIVERSIITY • BAMRASNARADURA INSTITUTE • RAMATHIBODHI HOSPITAL • VAJIRA HOSPITAL • Taksin HOSPITAL

THAILAND

CHON BURI

CAMBODIA

• CHONBURI REGIONAL Hospital • QUEEN SAWANGWATTANA MEMORIAL HOSPITAL

CHANTABURI • PRAPOKKLAO Hospital

PHNOM PENH • NATIONAL PEDIATRIC Hospital • SOCIAL HEALTH CLINIC


COLLABORATORS

INTERNATIONAL 9

Australia National Centre in HIV Epidemiology & Clinical Research, University of New South Wales, Sydney David A. Cooper (HIV-NAT co-director), Sean Emery, Sarah Pett, Cate Carey, Mark Boyd, Rebekah Puls, Carlo Dazo, David Courtney-Rodgers, Natalie Espinosa, Alli Humphries, Courtney Bendall, Gail Matthews, Greg Dore, Pip Marks, Amanda Erratt, Megan Evans, Enmoore Lin, Leanne Kearney, Nisha Seneviratne, Mee Ling Munier, Anthony Kelleher, Hila Haskelberg, Maria Arriaga, Christoph Boesecke, Jialun Zhou, Rebecca Oyomopito, Awachana Jiamsakul, Azar Kariminia and Matthew Law Monash University, Melbourne Infectious Diseases Unit, The Alfred Hospital, Melbourne Sharon Lewin and Jennifer Audsley Victorian Infectious Diseases Service, Royal Melbourne Hospital, Melbourne Joe Sasadeusz and Stephen Locarnini Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, Melbourne Scott Bowden Royal Perth Hospital Martyn French Cambodia Family Health International Laurent Ferradini National Center for HIV/AIDS, Dermatology and STDs (NCHADS) Mean Chhi Vun and Sarah Huffman National Pediatric Hospital & Social Health clinic, Phnom Penh Vonthanak Saphonn , Ung Vibol, Vannary Bun, Kea Chettra (study coordinator), Sam Sophan and Somanythd Chhay Meng Japan Research Institute of Tuberculosis Japan Anti-Tuberculosis Association, Tokyo, Japan Hideki Yanai and Norio Yamada The Netherlands Center for Poverty-related Communicable Diseases & University of Amsterdam Joep M A Lange (HIV-NAT co-director), Ferdinand Wit, Peter Reiss and Remko van Lewin and Janneke van de Wijgert

Erasmus University Medical Center Rotterdam Jan Nouwen Radboud University, Nijmegen Medical Center (Clinical Pharmacology) David Burger Switzerland Geneva University Medical School, Geneva University Hospital Bernard Hirschel and Alexandra Calmy The United States of America (USA) Lab of Neuro Imaging University of California Los Angeles, School of Medicine, Los Angeles Paul Thompson Johns Hopkins Center for Global Health Division of Infectious Disease, Baltimore Chloe Thio Memory and Aging Center at University of California, San Francisco Victor Valcour University of Missouri Behavioral Neuroscience/Neuropsychology, St. Louis, Missouri Robert Paul University of Hawaii, Manoa, Hawaii Cecilia M. Shikuma Wayne State University, Detroit Chokechai Rongkavilit

DOMESTIC Bangkok Children’s Hospital Tawee Chotpitayasunondh Chulalongkorn Hospital Chitsanu Panchareon, Gompol Suwanpimolkul, Opass Pucharoen, Pisith Tangkitvanich, Piyawat Komolmit, Rungsun Rerknimitr, Sukalaya Lerdlum, Surasith Chaithonwongwatthana, Vorasuk Shotelersuk and Wattanee Taweesith Family Health International Chaiwat Ungsedhapand and Nicolas Durier Pramongkrut Klao, Faculty of Medicine Pichai Saengcharnchai Ramathibodi Hospital Sasisopin Kiertiburanakul and Somnuek Sungkanuparph


10

Siriraj Hospital Kulkanya Chokephaibulkit, Surapol Suwanagool and Wichai Techasathit Taksin Hospital Supunnee Jirajariyavej The Thai Red Cross AIDS Research Center Mana Khongpatanayothin and Nittaya Phanuphak Vajira Hospital Warangkana Munsakul Chantaburi Prapokklao Hospital Chaiwat Ngampiyasakul Chiang Mai Chiang Mai University Virat Sirisanthana Nakornping Hospital Suparat Kanjanavanit Program for HIV Prevention and Treatment Jeffrey Parsons, Marc Lallemant and Sylvie Naar-King Sanpatong Hospital Virat Klinbuayaem Chiang Rai Chiangrai Regional Hopsital Pacharee Kantipong and Rawiwan Hansudewechakul Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association Maitri Oongern, Saiyud Moolphate, and Thittaya Kulprayong

Chonburi Chonburi Hospital Chureeratana Bowonwattanuwong Queen Savang Vadhana Memorial Hospital Wicharn Luesomboon Khon KaEn Srinagarind Hospital,Khon Kaen University Chulalak Sriheara, Maneerat Layton, Pagakrong Lumbiganon, Ploenchan Chetchotisakd, Pope Kosalaraksa and Siriluck Anunnatsiri Nonthaburi Bamrasnaradura Infectious Disease Institute Jurai Wongsawat, Weerawat Manosuthi and Wisit Prasithsirikul Central Chest Hospital Charoen Chuchottaworn National Health Security Office (NHSO) Sorakij Bhakeecheep and Winai Sawasdivorn Petchaburi Petchaburi Hospital Witaya Petdachai Surin Surin Hospital Pakarat Sangkla


OVERVIEW OF HIV-NAT STUDIES

This year has been an exciting time for hiv-nat with several noticeable changes. With the addition of new, young mds and study coordinators, hiv-nat has started to expand its studies to include fields not previously covered such as sexually transmitted diseases and prevention. New strategic studies are currently in the pipeline and are scheduled to start in 2010, replacing those studies which have been completed. Each category had at least 2 new studies scheduled to start in 2010 with others following suit, pending Ethics committee and funding approvals.

HIV-NAT studies cited in HIV treatment guidelines. One of HIV -NAT’s accomplishments in 2009 was the impact of its studies on treatment guidelines from various regions of the world. • 2 of our adult studies, 1 in HBV/HIV and 1 in HIV/ TB co-infection studies, were cited in WHO ’s Rapid Advice for antiretroviral therapy for HIV infection in adults and adolescents in December 2009. • 2 of our adult studies, 1 in hepatoxicity and 1 in first-line ART, and 1 pediatric pharmacokinetic study on PK (SQV/LPV/RTV) were cited by WHO’s Antiretroviral therapy of HIV infection in infants and children in resource-limited settings: towards universal access “Recommendations for a public health approach” 2006. • A total of 8 adult studies were cited by the DHHS’s Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, December 1st, 2009: 2 in hepatitis coinfection, 1 in TB coinfection, and 5 in HIV (1 PI, 1 NNRTI, 2 STI and 1 adverse event). • 3 adult (2NN, PK dPI and STACCATO) and 4 pediatric studies (PK SQV/LPV/RTV and dPI) were cited by the DHHS’s Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection February 23, 2009.

• 3 of our adult studies (SMART- when to start ART, 2NN and TMC125-C227) were cited by the PENTA 2009 guidelines for the use of antiretroviral therapy in paediatric HIV-1 infection. • 2 adults studies (SMART and 2NN) were cited in the British HIV Association guidelines for the treatment of HIV-1-infected adults with antiretroviral therapy 2008. HIV-NAT will continue to conduct research with the aim of influencing both national and international treatment guidelines for HIV infection. Funding for HIV-NAT studies ranged from its own drug fund to pharmaceutical companies, NIH and other various Thai granting agencies. Having a strong affiliation with the Faculty of Medicine, Chulalongkorn University, HIV-NAT has teamed up with several departments to request funding from the intramural grant and national granting agencies. This is not the first time HIV-NAT has teamed up with Chulalongkorn University to conduct clinical trials, but with their unwavering support in the past few years has made this partnership that much stronger, allowing HIV-NAT the chance to expand its horizons into International Graduate Programs for Ph.D, MD and Masters students.

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overall thai Support

12

governmental agencies

number of studies

Commission of Higher Education, Ministry of Education

6

Governmental Pharmaceutical Organization

2

Ministry of Public Health

4

National Health Security Office

5

National Research Council of Thailand

2

Social Security Office

2

Thai Research Fund

1

academic organizations Chulalongkorn University

3

The Royal College of Physician of Thailand

1

research organizations HIV-NAT

3

Knowledge Network Institute of Thailand

1

Thai Red Cross AIDS Reserach Centre

1

Overall International Support governmental agencies

number of studies

National Institute of Health (NIH)

12

pharmaceutical Partners Abbott

1

Avexa Limited

2

Boehringer Ingelheim Pharmaceuticals, Inc

3

Bristol-Myers Squibb

2

Chiron Corporation

2

GlaxoSmithKline

1

Gilead Sciences

2

Janssen-Cilag Ltd

1

Matrix

1

Merck & Co., Inc

4

NUMICO

1

ROCHE Pharmaceutical

3

Tibotec Pharmaceuticals

9

academic organizations Foundation for AIDS Research, United States (amfAR)

2

National Centre in HIV Epidemiology and Clinical Research (NCHECR), University of New South Wales (Sydney, Australia)

4

Research Institute of Tuberculosis Tokyo, Japan

1

University Medical Centre Nijmegen

1

Center for Poverty-related Communicable Diseases and University of Amsterdam research Organizations Pediatric European Network for Treatment of AIDS

1

Swiss HIV Cohort Study

3

funding Agencies Global Fund to Fight AIDS, Tuberculosis, and Malaria

4

charities Art AIDS Fund

2

Born to Live Charity

1

Living & Loving Charity

1


NUMBER OF STUDIES IN 2008 vs 2009

Viral co inf TB

categories

PK

2008 2009

categories

13

complete ongoing start

Cohort Strategy New Drug EAP Vaccine Ped 0 2 number of studies

4

6

8

10

12

14

16

STATUS OF STUDIES PK Viral co inf TB Cohort Strategy New Drug EAP Vaccine Ped 0 1 number of studies

PK Viral co inf TB Cohort Strategy New Drug EAP Vaccine Ped

2

3

4

5

Key to abbreviations Pharmacokinetic & Pharmacogenomics Studies Clinical Research Programs in Co-Viral & Viral Infections Clinical Research Programs in Co-Tuberculosis Infections Long term Cohort Analysis Strategy Studies New Drug Development Expanded Access Programs Vaccine Reseach Programs Pediatric and Youth Research Programs

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7

8


Pharmacokinetic and Pharmacogenomic Studies hiv-nat studies have demonstrated the impact of ethnicity on antiretroviral drug levels.

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Through our studies, we have documented that standard doses of some antiretroviral drugs result in high drug levels in Thais. In 2009, we directed our research focus to evaluating the genetic polymorphisms that may explain these high drug levels. We also undertook more studies to evaluate the use of lower doses of antiretrovirals particularly of the protease inhibitor drug class in adults, children and pregnant women. These pharmacokinetic and pharmacogenomic studies are a first step towards larger randomized studies of low versus standard dose of antiretrovirals. Such studies will be crucial in determining the appropriate antiretroviral dosages for Thais and other Asians in order to reduce toxicity and cost while maintaining efficacy. The pharmacokinetic and pharmacogenomic studies are a substantial part of the HIV-NAT studies, and include: polymorphism studies in which we evaluate several genetic polymorhisms and the effect on drug levels and the development of toxicity; therapeutic drug monitoring (TDM) studies of generic products; pharmacokinetic studies to assess PK parameters of lopnavir/ritonavir monotherapy in children and of darunavir/ritonavir in adults; low dose studies to assess clinical and immunological efficacy of reduced doses in Thai patients; and studies in pregnant women to assess PK profiles of antiretrovirals during pregnancy. Polymorphism Studies Pharmacogenomics of ATV/EFV HIV-NAT 103 A cross sectional study evaluating the impact and correlation between genetic polymorphism of antiretroviral drug(Atazanavir and Efavirenz) concentrations on long term immunologic and virologic response. Status: Analysing data Enrolled: 450 Collaborator/site: Chulalongkorn University Funding: The Royal College of Physicians of Thailand HIV-NAT 031 Since genetic polymorphisms may influence the drug levels of saquinavir, variants of CYP3A4, CYP3A5 and MDR-1 genes were investigated in Thai HIV-1 infected patients on saquinavir/ritonavir. This was done by using polymerase-chain reaction (PCR) and and high phase liquid chromatography (HPLC) with UV-detection. Status: Study completed Feb. 2009. In the process of writing manuscript. Enrolled: 230 patients Funding: Swiss Staccato Results: Bio-analysis done, statistical analysis in progress Nevirapine Toxicogenomics (BI1100.1452) HIV-NAT 069 A case-controlled toxicogenomics study was used to identify unique genetic polymorphisms in patients who have experienced symptomatic hepatotoxicity or severe

cutaneous toxicity within the first 8 weeks of nevirapine therapy (BI 1100.1452) by analyzing peripheral blood mononuclear cell DNA samples. Status: Study completed Feb. 2009. Currently analysing data for publication. Enrolled: 120 from HIV-NAT Collaborators/sites: Khon Kaen and Siriraj Funding: Boehringer Ingelheim Pharmaceuticals, Inc Therapeutic Drug Monitoring (TDM) Studies HIV-NAT 095 An open-label single arm prospective study evaluating the bioavailability of generic lopinavir/ritonavir tablets 200/50 mg in Thai HIV-infected patients Status: Interim analysis (N=37) is complete. status: the second phase is in the process of enrollment at this moment Enrolled: 100 HIV-infected patients without protease inhibitor failure in the past and stable on ARV Funding: Government Pharmaceutical Organization Results: The first 37 patients using generic lopinavir/ ritonavir in the standard dose of 400/100 mg BID had a mean (SD) Lopinavir Cmin of 7.3 (1.8) mg/L. None of the patients had subtherapeutic levels below 1.0 mg/L. Publications: Plasma concentrations of generic lopinavir/ritonavir in HIV type-1-infected individuals. Antivir Ther 2009;14(7):1001-4 HIV-NAT 118 This study will assess mid levels, safety and efficacy of tenofovir, lamivudine, and efavirenz in generic fixeddose combination tablets 300/300/600 mg in Thai HIV-infected patients at 48 weeks Target: 100 Status: Pending IRB approval Funding: Matrix Laboratory Pharmacokinetic Studies Lopinavir/ritonavir monotherapy in virally suppressed children HIV-NAT 077 Open label, multicentre observational cohort evaluating the efficacy (clinical, immunological, virological outcome), pharmacokinetics and safety of mLPV/r


monotherapy maintenance in Thai children after switching from dual boosted LPV/RTV/SQV with suppressed viral load. Status: Ongoing Enrolled: 40 children Collaborators/sites: Chulalongkorn Hospital and Khon Kaen University Funding: Global Fund for LPV/r Results: 85% of the children had VL<50copies/ml at 6 months after switching from dPI to mLPV/r with no effects on clinical, CD4, lipid profiles and fasting glucose Publications: Safety and Efficacy of Double Boosted Protease inhibitors, Saquinavir and Lopinavir/ritonavir, in Pre-treated Children at 96 Weeks. Antiviral Therapy 2009;14(2):241-8 HIV-NAT 115 This study will assess the pharmacokinetics of darunavir /ritonavir 600/100 OD versus 600/100 mg BID in combination with 2NRTIs in HIV pre-treated patients. Status: Pending IRB approval Funding: Commission of Higher Education (CHE) Low Dose Studies HIV-NAT 045 To assess clinical, immunological efficacy and pharmacokinetics of low- and standard dose of lopinavir/ritonavir in ARV PI na誰ve HIV-1 infected Thai children at 48 weeks. Status: Study closed on Feb. 2009 Enrolled: 24 children Funding: Commission on Higher Education, Ministry of Education Results: Low-dose lopinavir displayed adequate pharmacokinetics parameters and good efficacy as compared with standard-dose lopinavir in Thai children. Publications: Pharmacokinetics and 48 week efficacy of low-dose lopinavir/ritonavir in HIV-infected children. J Antimicrob Chemother 2009 Nov;64(5):1080-6 HIV-NAT 073 Since Thai patients express high plasma levels of individual NNRTI and bPI, this 24-hour pharmacokinetic study investigated the effects of lower dose atazanavir/ ritonavir (ATV/r 200/100) which was compared to 300/100 mg OD plus 2 NRTIs in HIV pre-treated Thai Patients. Status: Study completed Apr. 2008 Enrolled: 22 HIV infected patients with HIV RNA <50c/ ml and on ATV/r 300/100 OD+2NRTIs for at least 2 weeks Funding: Social Security Office Results: Atazanavir/ritonavir 200/100 mg once daily plus 2 nucleoside reverse transcriptase (NRTI) were significantly lower than 300/100 once daily dose but were comparable to historical Caucasian cohorts using the standard dose of 300/100 mg.None of the patients had subtherapeutic values at any given time. Bilirubin

concentration decreased significantly after dose reduction and viral load remained suppressed in all subjects. Publications: A Low Dose of Ritonavir-Boosted Atazanavir (200/100 mg) Provides Adequate Pharmacokinetics Parameters in Thai HIV-1 Infected Adults. Clin Pharmacol Ther 2009; 85(4):402-8 HIV-NAT 085 An open-label, two arm, randomized pharmacokinetic study with cross-over design of Pediatric Aluvia速 (Lopinavir/Ritonavir 100/25 mg BID) and generic Lopinavir/Ritonavir Tablet formulation (200/50 mg BID) in clinically and virologically stable HIV-1 infected Thai adults Status: Study completed Nov. 2009 Enrolled: 20 Thai HIV-1 infected individuals, stable on a PI containing HAART regimen and virologically suppressed Funding: Commission on Higher Education Publications: Preparing manuscript PregnanCY Studies SARA HIV-NAT 043 An open-label, multiple dose, multi centre two-group trial assessing the pharmacokinetic profile of saquinavir (Invirase速 new tablet formulation) 500mg tablet formulation combined with ritonavir (1,000/100mg q12h) in pregnant HIV-infected women. Status: Study completed Sept. 2009. Enrolled: 8 HIV-infected pregnant women Funding: ROCHE Pharmaceutical/ University Medical Centre Nijmegen Results: New saquinavir (SQV) tablet formulation generates adequate drug concentrations throughout the course of pregnancy and is safe to use. No SQV dose adjustment is needed during pregnancy. Publication: The pharmacokinetic , safety and efficacy of boosted saquinavir tablets in HIV type-1-infected pregnant women. Antivir Ther 2009;14(3):443-50 HIV-NAT 093 An open-label, multiple dose, one-group trial assessing the pharmacokinetic profile and safety of generic lopinavir/ritonavir tablets 200/50 mg tablet formulation (400/100 mg bid) in pregnant Thai HIV-infected women. Status: Enrollment is closed. Follow-up will be completed in Dec. 2009 Enrolled: 20 HIV-infected pregnant patients without protease inhibitor failure in the past Collaborators/sites: Thai Red Cross AIDS Research Centre and King Chulalongkorn Memorial Hospital Funding: Thai Red Cross AIDS Research Centre

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Clinical Research Programs in Co-Viral and Viral Infections

16

In 2009, hiv-nat published the only randomized study to date on the use of dual versus mono-hepatitis B therapy in hiv/Hepatitis B co-infected adults. This provided a basis for recommending dual hepatitis B therapy in several international treatment guidelines. Hepatitis B surface antibody recovery was also linked to the development of immune reconstitution syndrome in these studies leading to further trials to understand the pathogenesis of hepatitis B immune reconstitution syndrome in hiv-infected patients. This year, hiv-nat has also extended its research interest into studying influenza and its complications as part of the insight network. This will allow hiv-nat to utilize its research expertise in investigating other infectious diseases that are important to Thailand and the region. This section will discuss the HIV-NAT studies focusing on hepatitis b virus (HBV) infection in HIV-infected patients and Influenza A. In collaboration with several international partners, HIV-NAT is studying HBV resistance to tenofovir, HAART–associated hepatotoxicty, effect of HBV-active HAART on HBV DNA suppression and HBeAg seroconversion, liver disease progression and immune reconstitution. Two INSIGHT studies to describe adults with H1N1 infection will commence in 2010 as IRB approval is obtained. COLD STUDY Longitudinal HIV/HBV Cohort HIV-NAT 092 This is an extension of TICO/HIV-NAT 023 study. This is a prospective longitudinal cohort study of liver disease and HIV/HBV coinfection in the era of HAART in Thailand. It will assess the risk of HAART–associated hepatotoxicty, effect of HBV-active HAART on the magnitude and durability of HBV DNA suppression and HBeAg seroconversion, evolution and natural history of antiviral drug-resistant HBV in an HIV co-infected population, rate of liver disease progression, immune reconstitution and novel HBV epitopes associated with HBeAg seroconversion and/or disease flares. Status: Ongoing Enrolled: 47 patients from HIV-NAT with HIV/HBV co-infection who have completed 48 weeks of TICO HIV-NAT 023 Collaborators/sites: Multicenter AIDS Cohort Study (MACS), Baltimore site, U.S.A., The Alfred Hospital, the Royal Melbourne Hospital, Melbourne, Australia and St Vincent’s Hospital, Sydney, Australia, and Johns Hopkins Center for Global Health, Division of Infectious Disease, Baltimore, USA. Funding: NCHECR, Gilead Sciences, MOPH, Thai National Security Office (NHSO) and supplement grant from the NIH Results: TDF-containing HAART is highly successful in achieving HIV and HBV-related virological suppression in coinfected subjects initiating HAART in Thailand, irrespective of regimen. Further work is needed to

understand the mechanism(s) of the high rates of HBeAg loss and HBsAg seroconversion. Publications: 1) A randomized trial of combination hepatitis B therapy in HIV/HBV coinfected antiretroviral naïve individuals in Thailand. Hepatology. 2008 Oct;48(4):1062-9. 2) Defective hepatitis B virus DNA is not associated with disease status but is reduced by polymerase mutations associated with drug resistance. Hepatology. 2008 Sep; 48(3):741-9. HIV-NAT 098 This is a prospective, observational study in a multicentre, international cohort surveillance study for the detection of hepatitis B virus (HBV) resistance to tenofovir (TDF) in HIV-HBV co-infected patients Status: Ongoing Enrolled: 50 Thais out of 92 Collaborators/sites: Australia: St Vincent’s Hospital, Sydney, The Alfred Hospital, Melbourne and Melbourne Sexual health Centre (MSHC), Melbourne. Thailand: Thai Red Cross AIDS Research Centre and Department of Medicine, King Chulalongkorn Memorial Hospital, Bangkok Funding: Gilead Science Long-term HBV HIV-NAT 105 This study is a substudy of HIV-NAT 006. This is a long term cohort and cross section study assessing the effect of HBV-active HAART on magnitude and durability of HBV DNA suppression (HBV DNA <400 copies/mL), incidence and predictor of antiviral drugresistant HBV, effect of HBV-active HAART on HBeAg seroconversion, rate of liver disease progression, risk of HAART–associated hepatotoxicty, and effect of HAART on CD4 recovery and HIV RNA in HIV/HBV co-infected patients compared to HBV-negative/HIV infected patients Status: Analyzing data for manuscript publication Enrolled: 165 Funding: The Global Fund to Fight AIDS, Tuberculosis, and Malaria Results: TDF is highly effective in controlling HBV


17

replication in HIV-coinfected patients, regardless of previous LAM/FTC treatment or advanced HIV disease. TDF should always be included in HAART regimen for this population. Although none of TDF-mono developed HBV viral breakthrough, TDF surveillance for HBV resistance is warranted. Publications: Presented at CROI 2010 FLU002 HIV-NAT 122 An International Observational Study to Characterize Adults with Influenza A â&#x20AC;&#x201C;Pandemic H1N1 (H1N1v) INSIGHT H1N1v Outpatient Study (FLU 002) The purpose of this observational study is to describe participants in geographically diverse locations with influenza A-pandemic H1N1 (H1N1v) virus infection and their clinical course over a 14-day period following enrolment. Status: Pending IRB approval Enrollment (projected): 1,500 patients in Asia, Europe, Australia, North and South America Collaborators/sites: Chulalongkorn Hospital and Srinakarind Hospital/ Khon Kaen University Funding: National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) and carried out by the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) FLU 003 HIV-NAT 123 An International Observational Study to Characterize Participants with Influenza A-Pandemic H1N1 (H1N1v) Who Are Hospitalized with Complications of Influenza. INSIGHT H1N1v Influenza Hospitalization Study. The purpose of this observational study is to describe the characteristics and outcomes over a 60 day follow-up period of participants in geographically diverse locations who develop influenza A -- pandemic H1N1 (H1N1v) and who are hospitalized with complications resulting from influenza. Status: Pending IRB approval Enrollment (projected): 1,000 patients in Asia, Europe, Australia, North and South America

Collaborators/sites: Chulalongkorn Hospital, Srinakarind Hospital and Khon Kaen University Funding: National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) and carried out by the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) HIV-NAT 130 Mortality and Morbidity Risk Factor of Cytomegalovirus Viremia in AIDS Patients Starting Antiretroviral Therapy in Thailand. This is a retrospective observational cohort and nested case-control study to assess the possible association between CMV viremia and poor CD4 response to ART. Status: Pending IRB approval Target: 600 Funding: Abbott and Family Health International


Clinical Research Programs IN CO-TUBERCULOSis INFECTIONS hiv-natâ&#x20AC;&#x2122;s research interest has been in studying appropriate antiretroviral treatment options 18

for patients co-infected with tuberculosis. Our randomized study evaluating different dosing of nevirapine when used with rifampicin provided an important observation that using nevirapine lead-in dose for the first two weeks resulted in suboptimal nevirapine levels while increasing nevirapine maintenance dose to 600mg resulted in high rates of toxicity. We have also investigated the use of ritonavir-boosted protease inhibitors with rifampicin. In this coming year, hiv-nat is continuing studies in this area to include other antiretroviral drugs with rifampicin and rifabutin. Such studies are crucial to increase our ability to provide optimal care to patients with hiv and tuberculosis co-infection. The treatment of tuberculosis in HIV-infected patients remains a challenge. In 2009, HIV-NAT has conducted two pharmacokinetic (PK) studies, examining the PK parameters of nevirapine and indinavir.

Publications: Pharmacokinetics and 48-week efficacy of nevirapine: 400 mg versus 600 mg per day in HIVtuberculosis coinfection receiving rifampicin. Antivir Ther 2008;13(4):529-36

HIV/TB co-infection HIV-NAT 033 This is a randomized, open-label, two-arm prospective study examining the short-term efficacy and toxicity of using an increased dosage of NVP at 48 weeks after 2-6 weeks of RIF. Status: Study completed Aug. 2009 Enrolled: 46 Collaborators/sites: Central Chest hospital, Chiang Rai Hospital, Bamrasnaradura Institute, Phan Hospital and Mae Chan Hospital Funding: Research Institute of Tuberculosis Tokyo, Japan, MOPH, GPO Results: In rifampicin-treated patients, 200 mg NVP OD lead-in led to a significant short-term suboptimal NVP C12 level, while NVP 400 mg lead-in then 600 mg/day was associated with a high rate of NVP hypersensitivity. Forty-eight week efficacy was comparable. Thus, NVP 600 mg/day in rifampicin-treated patients is not recommended.

HIV-NAT 044 This is a pilot, prospective, 12-hour pharmacokinetic study investigating the safety and efficacy of ritonavirboosted indinavir 600/100mg bid in combination with nucleoside analogue reverse transcriptase inhibitors in antiretroviral naĂŻve HIV/TB co-infected patients receiving rifampicin containing anti-tuberculosis therapy at 48 weeks. Status: Study Completed Oct. 2009 Enrolled: 18 Funding: Commission on Higher Education, Ministry of Education and National Health Security Office (NHSO) Results: 80% of Indinavir (IDV) levels were suboptimal when used with rifampicin (RIF) even though the majority of the patients had undetectable VL at week 48. Half of the patients developed asymptomatic ALT elevations within 1 week but these declined over time and only 10% had symptomatic hepatoxicity after 16 weeks. All of our patients were virologically suppressed at week48. Publications: Presented at IAS 2009


Long term cohort analysis

Antiretroviral therapy was introduced in Thailand in the mid 1990s. Since then, much progress in hiv treatment has been accomplished. However, there is limited information on the long term efficacy, tolerance and side effects of antiretroviral therapy in Thais. The first group of hiv-natâ&#x20AC;&#x2122;s patients enrolled in our study was in 1995. We have now approximately 1500 patients in active follow up. The hiv-nat long term cohort study does not only allow us to provide high quality care to our patients but also to provide us with the opportunity to assess long term effects of antiretrovirals in Thais who have been on treatment for up to fourteen years. HIV-NAT has a large, long-term, post study cohort of HIV-infected patients who previously participated in HIV-NAT study protocols. This cohort provides us with an opportunity to collect information on safety and efficacy of HAART, short term and long term toxicity, adherence, morbidity and mortality. We also have a similar long-term follow-up study of safety and efficacy of antiretroviral therapy for HIV positive children who have previously participated in HIV-NAT study protocols. Our centre is also one of the data contributing sites for the TREAT Asia HIV Observational Database and the TREAT Asia paediatric HIV Observational Database. HIV-NAT 006 This is a long-term, post study cohort of HIV-infected patients who previously participated in HIV-NAT study protocols. Information collected from this cohort will provide further insights into the long-term safety and durability of various antiretroviral therapeutic approaches, efficacy of HIV viral load and CD4 cell counts as predictors of disease progression, mortality, resistance profiles, adherence, immune recovery syndrome, opportunistic infections or malignancies, incidence of lipodystrophy, other metabolic complications, cardiovascular, renal, hepatic, and endocrine function, skin, gastrointestinal system and urogenital tract problems, and quality of life. Status: Ongoing Enrolled: 1200 Funding: HIV-NAT Drug Fund, Division of AIDS Ministry of Public Health (MOPH) Thailand, National Health Security Office (NHSO), Social Security Office (SSO), Global Fund, Roche, Bristol-Myers Squibb, Merck & Co., Tibotec Pharmaceuticals Ltd, Gilead Science Publications: 1 Anal squamous intraepithelial lesions among HIVpositive and HIV-negative men who have sex with men in Thailand. Sex Transm Infect 2009 Dec; 85(7):503-7 2 Nadir CD4 count and monthly income predict cervical squamous cell abnormalities in HIV-positive women in a resource-limited setting. Int J STD AIDS. 2008 Aug; 19(8):529-32 3 Long-term efficacy and safety of first-line therapy with once-daily saquinavir/ritonavir. Antivir Ther 2008;13(3):375-80 4 Changes in metabolic toxicity after switching from stavudine/didanosine to tenofovir/lamivudine

a Staccato trial substudy. J Antimicrob Chemother 2008 Jun;61(6):1340-3 5 Interruptions of tenofovir/emtricitabine-based antiretroviral therapy in patients with HIV/hepatitis B virus co-infection. AIDS. 2008 Jan 2;22(1):152-4 6 Preference for CD4-guided versus continuous HARRT in Thailand. AIDS Care. 2008 Mar;20(3):327-30 7 A prevalence of posttransplantation cancers compared with cancers in people with human immunodeficiency virus/acquired immunodeficiency syndrome after highly active antiretroviral therapy. Transplant Proc 2008 Oct;40(8):2677-9 8 Ferritin levels during structured treatment interruption of highly active antiretroviral therapy. HIV Med 2007 Sep;8(6):388-95 9 Supersensitive Viral Load Assay in Predicting CD4Guided Treatment Failure. The Open Virology Journal 2008, volume 2, pp. 69-73 (5) HIV-NAT 015 This is a long-term follow-up study of safety and efficacy of antiretroviral therapy for HIV positive children who have previously participated in HIV-NAT study protocols. Status: Recruitment opened in 2002 & is ongoing Enrolled: 232 children and 52 HIV-infected parents. Collaborator/site: Chulalongkorn Hospital Funding: The Thai National Security Office (NHSO), Thai Ministry of Public Health, Global fund, the Born to Live charity, ART AIDS Fund and Living & Loving charity Publications: Pattern and predictors of immunologic recovery in human immunodeficiency virus-infected children receiving non-nucleoside reverse transcriptase inhibitor-based highly active antiretroviral therapy. Pediatr Infect Dis J 2009 Jun;28(6):488-92 PREDICT sub study-PREDICT Cohort HIV-NAT 035.3 Extension for HIV-NAT 035 Status: Recruitment closed September 2008. Last follow-up will be in July 2011. Enrolled: 180 Thai/120 Cambodian children Site PIs in Thailand: HIV-NAT and Chulalongkorn University: Kiat Ruxrungtham, Bamrasnaradura Institute: Jurai Wongsawat , Khon Kaen University: Pope Kosalaraksa, Queen Savang Vadhana Memorial Hospital: Wicharn Luesomboon, Nakornping Hospital:

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Suparat Kanjanavanit, Chiangrai Regional Hospital: Rawiwan Hansudewechakul, PHPT: Marc Lallemant, and Prapokklao Chantaburi: Chaiwat Ngampiyasakul Site PIs in Cambodia: National Center for HIV/AIDS, Dermatology and STDs (NCHADS): Mean Chhi Vun and Vonthanak Saphonn Funding: National Research Council of Thailand TAHOD The Treat Asia HIV Observational Database HIV-NAT 048 This study collects observational data on HIV-infected patients from a number of sites in several Asian countries. The information gathered will help develop more effective research and treatment programs for people with HIV/AIDS in the region. Status: Latest data transfer was on Sept. 2009. Study is still ongoing. Enrolled: 100 Collaborator/site: Chulalongkorn Hospital Coordinating Center: National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia Funding: Foundation for AIDS Research, United States (amfAR) Publications: AIDS-related and non-AIDS-related mortality in the Asia-Pacific region in the era of combination antiretroviral treatment. AIDS. 2009 Nov.13;23(17):2323-36

Death Study â&#x20AC;&#x201C; observational study HIV-NAT 076 This is an observational and cross sectional study assessing the rate and trend of all causes of deaths, etiology of death and characteristics associated with or predictive of all causes of death and AIDS-related death in patients treated with HAART from 1 Jul. 1996 to 31 Dec. 2009. Status: Analyzing data and writing manuscript Enrolled: 1200 Results: pending analysis TApHOD TREAT Asia Pediatric HIV Observational Database HIV-NAT 080 This study is an HIV pediatric HIV observational database collecting HIV clinical data (demographic information and other variables such as HIV-exposure category, HIV subtype, AIDS-defining illnesses, and treatment history) from countries located in the AsiaPacific region. This information will be used to develop more effective research and treatment programs for people with HIV/AIDS in the region. Status: Ongoing. Latest data transfer was on Sept. 2009 Enrolled: On going Coordinating Center: National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia Funding: Foundation for AIDS Research, United States (amfAR) HIV-NAT 082 This is a cross sectional study assessing the predictors of adherence to ARV in Thailand and understand which patients might be at risk for non-adherence to antiretroviral agents. This is done by using qualitative and quantitative methodologies. Status: Study closed Aug. 2009 Enrolled: 318 Collaborators/sites: HIV-NAT TRCARC, Srinakarind Hospital, Khon Kaen and Chulalongkorn Hospital Bangkok Funding: University of New South Wales Results: This study compared two adherence tools and found that a 30 day visual analogue scale had higher sensitivity and specificity in predicting undetectable viral load than another questionnaire. In multivariate models of adherence predictors, attending a clinic not staffed by HIV specialists and primary education or less were associated with poor adherence to ART. The most common reason cited by patients who missed medications in the previous month was not wanting to act in a way that caused someone else to be suspicious about their disease. Publications: Assessing adherence in Thai patients taking HAART Int J STD AIDS (In Press)


Strategy Studies

Strategy studies aim to assess the best way to utilize therapy effectively. hiv-nat has been a leader in several strategic trials in the past including interleukin-2 treatment and structured treatment interruption. In 2009, hiv-nat collaborated with a group of Thai experts to launch a study evaluating protease inhibitor monotherapy in treating adults who have failed first line therapy. We have the largest on-going cohort of children on protease inhibitor monotherapy as maintenance second line treatment. HIV-NAT is a participating centre for several international strategy studies, including stalwart, altair, start, esprit and bite. BITE HIV-NAT 042 A randomized, double-blind, controlled study, multicentre trial assessing the effect of taking NR100157 for 1 year in HIV-1 Positive Adults not on antiretroviral therapy Status: Study closed Apr. 2009 Enrolled: 27 HIV-infected patients not on ARV Collaborators/sites: Multi-centre study (AustraliaEurope-USA) Funding: NUMICO/Danone Research Results: Subjects with the food product had a significant slower decline in CD4+ cell count compared to the placebo group Publications: Publication in preparation, first results published at ICAAC 2009 Duet (TMC 125-C206/C217) HIV-NAT 060 A phase III, randomized, double-blind, placebocontrolled trial investigating the efficacy, tolerability and safety of TMC125 (200 mg BID) in combination with TMC114/RTV (600/100 mg BID) and an investigator-selected OBR of at least 2 antiretrovirals in HIV-1 infected subjects with limited to no treatment options. All subjects had at least 1 documented non-nucleoside reverse transcriptase inhibitor (NNRTI) resistanceassociated mutation, HIV-1 plasma viral load > 5000 RNA copies/mL at screening and at least 3 documented primary protease inhibitor (PI) mutations. Status: Recruitment closed and study ongoing Enrolled: 2 patients at HIV-NAT Collaborators/sites: Chulalongkorn Hospital [HIVNAT], Siriraj Hospital, Mahidol University, Srinagarind Hospital, Khon Kaen University Funding: Tibotec Pharmaceuticals Ltd ESPRIT HIV-NAT 065 This is a randomized, open label, phase III international study of subcutaneous recombinant interleukin-2 (Proleukin®) in patients with HIV infection, CD4+ lymphocyte ≥ 300 cells/mm3 and with antiretroviral therapy (ARV) or as antiretroviral therapy alone. Recombinant IL-2 was given in 5 day cycles.

The primary endpoint of the study was disease progression. Status: Completed Enrolled: 256 in Thailand Collaborators/sites: Chulalongkorn Hospital [HIVNAT], Siriraj Hospital, Mahidol University, Srinagarind Hospital, Khon Kaen University, Chonburi Hospital and Chiang Rai Hospital Funding: National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda (NIH), Chiron Corporation, The Government Pharmaceutical Organization (Thailand), Division of AIDS, Ministry of Public Health, Thailand, Merck and Bristol-Myers Squibb (Thailand) and The Government Pharmaceutical Organization (Thailand) Results: Despite a substantial and sustained increase in CD4+ cell count, as compared with antiretroviral therapy alone, interleukin-2 plus antiretroviral therapy yielded no clinical benefit. Publications: Interleukin-2 therapy in patients with HIV infection. N Engl J Med. 2009 Oct. 15;361(16):1548-59 STALWART HIV-NAT 068 A randomized, open-label, international study of subcutaneous recombinant Interleukin-2 (rIL-2, Aldesleukin) with and without concomitant antiretroviral therapy in patients with HIV-1 infection and CD4+ cell counts ≥ 300/mm3. Status: Study terminated after the results of the ESPRIT study were available and re-opened February 2009 to continue monitoring the safety of participants until 2011 Enrolled/target: 40 at site HIV-NAT/Worldwide 300 subjects from 12 countries. Target for Thailand was 60 subjects. Regional Trials Coordinating Centre: National Centre in HIV Epidemiology and Clinical Research, Sydney Collaborators/sites: Chulalongkorn Hospital [HIVNAT], Srinagarind Hospital, Khon Kaen University and Chiang Rai Hospital Funding: National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) and Chiron Corporation Results: Patients on antiretroviral therapy and IL-2 had sustained increases in CD4 but did not reduce risk of opportunistic infections or death. Also, it did not improve the health outcomes for people infected with HIV.

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Altair HIV-NAT 072 A phase IIIb/IV, international, randomised, open-label study comparing the safety and efficacy of three different regimens of combination antiretroviral therapy in treatment-naïve, HIV-infected subjects over a two-year period. Magnectic Resonance Spectroscopy Substudy (MRS Substudy) assessed cognitive function of 30 patients (10 per arm) for neurological impairment by administering MRS, MRI and automated cognitive function assessments at baseline, week 48 and week 96 in the main study. Status: Enrollment completed Mar. 2008. The study was extended another 48 weeks and is currently ongoing. Enrolled: 65 Collaborators/sites: only HIV-NAT site for Thailand, several sites from other countries Funding: National Centre for HIV Epidemiology and Clinical Research, Sydney, Australia Results: The MRS sub study is the first study to prospectively describe different changes in cerebralfunction testing parameters between different cARTs. Greater improvements in neuronal recovery (NAA/ Cr ratio) were observed in recipients of TDF/FTC plus EFV (arm1) and greater improvements in NC function testing observed in recipients of TDF/FTC plus ABC/ AZT (arm3). Publications: Choice of combination antiretroviral therapy (cART) alters changes in cerebral function testing after 48 weeks in treatment-naïve, HIV-1 infected subjects commencing cART: a randomised controlled study. CID (in Press) HIV STAR (The HIV Second-line Therapy AntiRetroviral study in patients who failed NNRTI-based regimens) HIV-NAT 079 A multicentre, randomized, open label, non-inferiority comparison study evaluating the efficacy and safety between 2 NRTIs plus lopinavir/ritonavir (LPV/r) and LPV/r monotherapy in patients failing a standard NNRTI-based treatment regimen at 48 weeks Status: Ongoing Enrolled/target: completed enrolment 200 cases in November 2009 Collaborators/sites: TRCARC, Chulalongkorn University, Bamrasnaradura Institute, Khon Kaen University, Chonburi Hospital, Chiang Rai Regional Hospital, Ramathibodi Hospital, Sanpatong Hospital, Taksin Hospital, and BMA Medical College and Vajira Hospital Funding: The National Health Security Office (NHSO), The Swiss HIV Cohort Study, National Research Council of Thailand (sponsored substudy for the effects of LPV/r monotherapy in central nervous system and genital secretion)

START (Strategic Timing of AntiRetroviral Treatment) HIV–NAT 097 A Multicenter Study of the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) The purpose of this randomized study is to determine whether immediate initiation of antiretroviral treatment (ART) is superior to deferral of ART until the CD4+ declines below 350 cells/mm3 in terms of morbidity and mortality in HIV-1 (subsequently referred to as HIV) infected persons who are antiretroviral naïve with a CD4+ count above 500 cells/mm3. The study will proceed in two phases: (1) a pilot phase, involving at least 900 participants; and (2) a definitive phase, expanding enrollment to an estimated 4,000 participants. Upon completion of the pilot phase, a recommendation will be made to the sponsor (DAIDS, NIAID, NIH) concerning whether the study should be expanded and prolonged into a definitive study. Successful completion of the pilot phase requires enrollment of at least 900 participants in 1 year by 70 designated INSIGHT sites. Additional sites, sponsored by organizations other than DAIDS, will also participate in the pilot and definitive phase. Status: Enrolment in Thailand started in Jan. 2010. Ongoing. Enrolled: 5 (may change this later) Collaborators/sites: Srinagarind Hospital and Khon Kaen University Sponsor: The National Institute of Allergy and Infectious Diseases (NIAID) Division of AIDS (DAIDS) National Institutes of Health (NIH) Arterial Elasticity substudy HIV-NAT 097.1 This study will compare the changes in arterial elasticity over an average follow-up period of 4.5 years in patients receiving immediate or deferred ART. Status: Pending IRB approval Target: 40 Collaborators/sites: Srinagarind Hospital and Khon Kaen University Funding: University of Minnesota Minneapolis, Copenhagen HIV Programme (CHIP), Medical Research Council (MRC) Clinical Trials Unit (London, United Kingdom), National Centre in HIV Epidemiology and Clinical Research (NCHECR), University of New South Wales (Sydney, Australia), The Institute for Clinical Research at the Veterans Affairs Medical Center (Washington D.C., USA), The National Heart, Lung & Blood Institute National Institutes of Health and Australian National Health and Medical Research Council (NH&MRC).


Expanded Access Programs hiv-nat has committed its resources to provide patients in need with life saving medications

through the Expanded Access Programs by pharmaceutical sponsors. These programs allow patients to access antiretrovirals at no cost prior to their availability in the market. 23

For patients who have failed multiple antiretroviral regimens and have no further treatment options, HIV-NAT is currently providing Darunavir or Raltegravir through two expanded access programs. DANCE Darunavir is Accessible to Needy Treatmentexperienced patients as Compassionate use Entry This project is to provide Darunavir for HIV-1 infected patients who have failed multiple antiretroviral (ARV) regimens with limited to no treatment options. All eligible patients will get Darunavir free of charge from the sponsor until they can receive reimbursement from the Thai government Status: Ongoing Enrolled: 150 patients in Thailand with 7 at HIV-NAT Sponsor: Janssen-Cilag Ltd

MK -0518 HIV-NAT 087 This is an Early Access Program (EAP) for Raltegravir (MK-0518) in combination with an optimized background antiretroviral therapy (OBT) in highly treatment experienced HIV-1 infected patients with limited to no treatment options due to resistance or intolerance to other regimens. Subjects must have documented resistance to NNRTIs or clinical failure on an NNRTI regimen and have documented resistance to at least 1 NRTI at least 1 PI. Status: Recruitment completed Enrolled: 25 Funding: Merck & Co., Inc

New Drug Development hiv-nat is committed to the fieldâ&#x20AC;&#x2122;s quest to evaluate new drug options for patients. Through

partnerships with pharmaceutical companies, we have been involved in various trials to evaluate the use of new drugs and new drug classes in Thais. In 2009, we conducted studies on new non-nucleoside reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors and entry inhibitors in both adults and children. These trials are extremely important particularly to provide access to new treatments in adults and children who have failed all current drug classes. A number of new antiretroviral drugs are under investigation at HIV-NAT, some as part of a worldwide trial. Studies that are ongoing in 2009, include dose finding of TMC278; efficacy, safety and tolerability of TMC114; and evaluation of tipranavir and darunavir. ARTEMIS (TMC114-C211) HIV-NAT 067 A randomized, controlled, open-label trial comparing the efficacy, safety and tolerability of TMC114/ritonavir versus lopinavir/ritonavir in treatment-naĂŻve HIV-1 infected subjects. Status: Study completed Sept. 2009. This study was extended another 96 weeks. Ongoing. Enrolled: 9 patients enrolled, 3 prematurely withdrew Funding: Tibotec Pharmaceuticals Ltd Results: DRV/r 800/100 mg qd was non-inferior to LPV/r 800/200 mg at 48 weeks. Also, DRV/r 800/100 mg had a more favorable safety profile. Patients with HIV-1 RNA at least 100 000 copies/ml performed better with DRV/r 800/100 mg. DRV/r 800/100 mg is very effective in reducing VL and well tolerated as a once-daily,

first-line treatment option for treatment-naive patients. Publications: 1 Efficacy and safety of once-daily darunavir/ritonavir versus lopinavir/ritonavir in treatment-naive HIV-1infected patients at week 48. AIDS. 2008 Jul. 31;22(12):1389-97 2 Once-daily darunavir/ritonavir vs. lopinavir/ritonavir in treatment-naive, HIV-1-infected patients: 96-week analysis. AIDS. 2009 Aug. 24;23(13):1679-88 POTENT study BI1182.71 (PrOspecTive EvaluatioN of Tipranavir vs. Darunavir in Treatment Experienced Patients) HIV-NAT 084 An international, multi-centre, prospective randomized, open-labelled, phase IIIb study comparing the safety and efficacy of ritonavir-boosted tipranavir (TPV/r 500mg/200mg BID) to that of darunavir (DRV/r 600mg/100mg BID) with an investigator selected optimized background regimen (OBR) in three-class (NRTI, NNRTI, and PI) treatment-experienced patients


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with resistance to more than one PI. Status: DSMB stopped the study due to slow rate of recruitment. Study closed Apr. 2009. Enrolled/target: 2 at HIV-NAT/800 worldwide Funding: Boehringer Ingelheim AVX-301 HIV-NAT 088 An international, multi-centre, randomized, double blind, dose confirming phase IIb/III study comparing the safety, efficacy and tolerability of apricitabine (ATC) versus lamivudine (3TC) in treatment-experienced HIV-1 infected patients with the M184V/I mutation in reverse transcriptase by looking at CD4, CD8 and nucleoside associated mutations (NAMs). Status: First patient enrolled Jun. 2008. Ongoing. Enrolled/target: 9 at HIV-NAT/970 worldwide Funding: Avexa Limited ODIN (TMC114-TiDP31-C229) HIV-NAT 089 A randomized, open-label trial comparing efficacy, safety and tolerability of DRV/rtv (800/100 mg) q.d. versus DRV/rtv (600/100 mg) b.i.d. in early treatmentexperienced HIV-1 infected subjects at week 48. This study aims to show non-inferiority margin (delta) of 12% when administered in combination with an individually selected OBR. Status: Study completed Oct. 2009

Enrolled/target: 21 at HIV-NAT/Target at HIV-NAT is 8 patients; 68 patients for Thailand Collaborators/sites: Siriraj hospital, Bamrasnaradura Institute, Ramathibodi Hospital and Khon Kaen University hospital Funding: Tibotec Pharmaceuticals Ltd THRIVE (TMC278-C215) HIV-NAT 091 This is a phase III, randomized, double-blind trial of TMC278 25 mg q.d. versus efavirenz 600 mg q.d. in combination with a background regimen consisting of 2 nucleoside/nucleotide reverse transicriptase inhibitors in antiretroviral-na誰ve HIV-1 infected subjects. Status: Ongoing Enrolled: 18 Funding: Tibotec Pharmaceuticals Ltd AVX-303 HIV-NAT 101 A phase III, open-label, 96-week extension study of protocol AVX-301 or AVX-302. This study will assess the safety of apricitabine in treatment-experienced HIV-1 infected patients from AVX-301 or AVX-302 or who have met the criteria for open-label access to ATC because of virologic failure/lack of response. Status: Study terminated Apr. 2009 Enrolled: 0 Funding: Avexa

Vaccine Research Programs hiv-nat continues to be involved in the development of hiv vaccines for Thais. We have

conducted a phase I study of hiv vaccine designed to illicit immune response to prevent infection from common hiv subtypes found in Thailand. hiv-nat acknowledges the importance of having adequate immunity to common infections in hiv-infected patients particularly in children who are often immunized while severely immunosuppressed. hiv-nat has conducted studies to evaluate immunity and provide re-immunization to children to prevent hepatitis B and varicella infections. Three vaccine studies are ongoing in 2009; hepatitis B vaccination in adults and in children, and one study assessing the varicella vaccine in HIV-infected children. HIV-NAT 036 This study assessed the efficacy of HBV vaccine response and prevalence of occult HBV infection in isolated anti HBc between HIV infected and HIV uninfected Thai patients. Status: Study completed Sept. 2009 Enrolled: 120 HIV infected and 60 HIV-uninfected, isolated antiHBc patients Funding: Swiss HIV cohort study, Staccato project Results: Analyzing data for manuscript publication Publications: pending

The Australia-Thai Vaccine Program HIV-NAT 064 This was a randomised, double blind, placebo-controlled 52 week study, phase I clinical trial evaluating the safety and immunogenicity of a candidate prophylactic pHIS-HIV-AE DNA Prime and recombinant fowlpox (rFPV) -HIV-AE Boost HIV vaccination strategy in healthy volunteers at low risk of HIV infection. Status: Study was prematurely stopped on May 2009 Enrolled/target: 8/24 Funding: National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia Results: When the interim analysis was done at 16 weeks of follow-up, the results showed that the vaccine


was well tolerated with mild to moderate local and systemic reactions. No serious adverse events were observed over 24 weeks post vaccination. CD4 and CD8 responses were below the threshold for a positive response. Publications: pending

Hepatitis B vaccine in HIV-infected children HIV-NAT 107 This is an open label, randomized control trial assessing the efficacy between intradermal (ID) and intramuscular (IM) delivery routes of hepatitis B vaccine in HIV-infected children on highly active antiretroviral therapy (HAART). Status: Ongoing

Enrolled: 80 Collaborator/site: Chulalongkorn Hospital Funding: Art AIDS Fund (AAF) HIV-NAT 111 This is an open label, single arm study assessing the safety and efficacy of varicella vaccine in HIV-infected children treated with highly active antiretroviral therapy (HAART). Status: Ongoing Enrolled: 60 Collaborator/site: Chulalongkorn Hospital Funding: Division of Infectious Diseases, Chulalongkorn University

Pediatric and Youth Research Programs

Worldwide, there is a shortage of pediatric hiv experts and of pediatric hiv studies. This has resulted in delays in launching new medications and treatments for children. hiv-nat is committed to improving the lives of children and youth with hiv infection. We have led studies to evaluate timing to initiate first line antiretroviral therapy, neurocognitive impairment from hiv and treatment options for children who have failed first line antiretroviral therapy. We also give utmost importance to the psychosocial aspect of pediatric hiv care. With support from three international charities, we have been able to help our children and their families through group activities, home visits, supplemental living cost and scholarships. In 2009, HIV-NAT pediatric team has 2 completed studies, 10 ongoing studies, and 3 new studies. Two third of the studies were HIV-NAT generated and 5 were multicentre multinational trials with 8 sites in Thailand and 2 sites in Cambodia. The main anti-retroviral therapy was supported by the Thai National Health Security Office. PREDICT (Paediatric Randomized to Early vs Deferred Initiation in Cambodia and Thailand) HIV-NAT 035 An open label, randomized phase III study comparing early versus deferred (starting HAART when CD4+ falls below 15%) initiation of HAART in anti-retroviral-na誰ve children aged 1 to 12 years with CDC paediatric clinical classification category A or B and CD4+ between 15 to 24%. (NCT 00234091) Status: Recruitment closed Sept. 2008. Last follow-up will be in Jul. 2011. Enrolled: 180 Thai/120 Cambodian children Site PIs in Thailand: HIV-NAT and Chulalongkorn University: Kiat Ruxrungtham, Bamrasnaradura Institute: Jurai Wongsawat , Khon Kaen University: Pope Kosalaraksa, Queen Savang Vadhana Memorial Hospital: Wicharn Luesomboon, Nakornping Hospital: Suparat Kanjanavanit, Chiangrai Regional Hospital: Rawiwan Hansudewechakul, PHPT: Marc Lallemant, and Prapokklao Chantaburi: Chaiwat Ngampiyasakul

Site PIs in Cambodia: National Center for HIV/AIDS, Dermatology and STDs (NCHADS): Mean Chhi Vun and Vonthanak Saphonn Funding: National Institute of Allergy and Infectious Diseases (NIAID): Comprehensive International Program of Research on AIDS (CIPRA) grant. Antiretroviral medication is provided at no cost by GlaxoSmithKline (AZT, 3TC and Abacavir), Boehringer Ingelheim (nevirapine), Merck (efavirenz), Abbott (lopinavir/ritonavir) and Hoffmann La Roche (nelfinavir). Publications: Lessons from a multicentre paediatric HIV trial. Lancet. 2008 Aug. 2;372(9636):356-7 PREDICT sub study HIV-NAT 035.1 This sub study assessed the effect of immediate versus deferred antiretroviral initiation on neurodevelopment in children with HIV in Cambodia and Thailand. Neurodevelopment was assessed every six months. The primary outcome is the neurodevelopment functions in the immediate arm compared to the deferred arm at week 144. Status: Recruitment closed Sept. 2008. Last follow-up will be in Jul. 2011. Enrolled: 180 Thai/120 Cambodian children Site PIs in Thailand: HIV-NAT and Chulalongkorn University: Kiat Ruxrungtham, Bamrasnaradura Institute: Jurai Wongsawat, Khon Kaen University: Pope Kosalaraksa, Queen Savang Vadhana Memorial

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Hospital: Wicharn Luesomboon, Nakornping Hospital: Suparat Kanjanavanit, Chiangrai Regional Hospital: Rawiwan Hansudewechakul, PHPT: Marc Lallemant, and Prapokklao Chantaburi: Chaiwat Ngampiyasakul Site PIs in Cambodia: National Center for HIV/AIDS, Dermatology and STDs (NCHADS): Mean Chhi Vun and Vonthanak Saphonn Funding: National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Mental Health (NIMH), National Institute of Child Development (NICHD) PREDICT sub study- Micronutrient HIV-NAT 035.2 This sub study assessed the impact of selenium/ zinc levels on HIV disease and treatment response in children. Status: Recruitment closed Sept. 2008 Last follow-up will be in Jul. 2011 Enrolled: 180 children Site PIs in Thailand: HIV-NAT and Chulalongkorn University: Torsak Bunupuradah and Kiat Ruxrungtham, Bamrasnaradura Institute: Jurai Wongsawat , Khon Kaen University: Pope Kosalaraksa, Queen Savang Vadhana Memorial Hospital: Wicharn Luesomboon, Nakornping Hospital: Suparat Kanjanavanit, Chiangrai Regional Hospital: Rawiwan Hansudewechakul, PHPT: Marc Lallemant, and Prapokklao Chantaburi: Chaiwat Ngampiyasakul Site PIs in Cambodia: National Center for HIV/AIDS, Dermatology and STDs (NCHADS): Mean Chhi Vun and Vonthanak Saphonn Funding: National Institute of Allergy and Infectious Diseases (NIAID) PENTA 11 HIV-NAT 066 A long term follow-up study assessing whether children with HIV infection undergoing planned ART interruptions are disadvantaged clinically, immunologically, virologically or neurologically from periods of time off ART. Status: Ongoing until 2013 Enrolled: All 9 children completed their first year neurocognitive study (IQ test) in May 2009 Collaborator: Chulalongkorn Hospital Funding: Pediatric European Network for Treatment of AIDS (PENTA) MET-THAI (Motivation Enhancement Therapy for Health Risk Behaviors in HIV+ Thai Youth age 16-24 years) HIV-NAT 078 To assess the effectiveness of Motivation Enhancement Therapy in reducing sexual risk behaviours in HIV-

infected Thai youth by measuring their condom use. Status: Ongoing Enrolled/target: 83/130 Collaborators/sites: Thai Red Cross AIDS Research Centre and Chulalongkorn Hospital Funding: National Institute of Health (NIH) HIV-NAT 015.2 This is a pilot study comparing total brain volume and frontal lobe volume by Tensor Based Morphometry (TBM) and corpus callosum fractional anisotropy by Diffusion Tensor Imaging (DTI) in HIV infected and healthy children. Status: Study completed. Results are being analyzed to expand the study. Enrolled: 6 children Collaborator/site: Chulalongkorn Hospital HIV-NAT 086 A multicentre, retrospective data collection study comparing virological efficacy, as measured by the proportions of children with HIV RNA below 400 and 50 copies/ml, of two ART regimens containing either single- and double ritonavir-boosted PI as second line therapy over 48-week period in children failing non nucleoside reverse transcriptase inhibitor (NNRTI)based treatment. Status: Study completed Aug. 2009. In the process of analyzing data and writing manuscript. Enrolled: 240 Site Pis in Thailand: Virat Sirisanthana, Tawee Chotpitayasunondh, Kulkanya Chokephaibulkit, Rawiwan Hansudewechakul, Pope Kosalaraksa, Witaya Petdachai and Gonzague Jourdain Funding: Commission on Higher Education, Ministry of Education Results: Double-boosted SQV+LPV/r was effective and safe alternative for a second-line regimen in children. Hypercholesterolaemia needs close monitoring. PI dose reduction should be considered. NV 20911 HIV-NAT096 An open, randomized, controlled multicenter trial, phase I/II study assessing the safety and efficacy of Invirase速 boosted with ritonavir in HIV-1 infected infants and children between 4 months and 6 years old. Status: Enrollment closed Enrolled/target: 3/24 Collaborator/site: Chulalongkorn Hospital Funding: Roche


PAINT (TMC 278-C213) HIV-NAT 099 This is a phase II, open label, single arm multicenter trial evaluating the pharmacokinetics, safety, tolerability and antiviral activity of Rilprivirine (TMC 278-C213) in na誰ve HIV-infected adolescents between the ages of 12-18 years Status: Enrollment will begin at the end of 2009 Collaborator/site: Chulalongkorn Hospital Funding: Tibotec Pharmaceuticals HIV-NAT 106 This study has assessed the holistic work to prevent and solve problems for children and youth living with HIV in Thailand by questionnaires and interviewing. Status: In the process of analyzing data and writing the manuscript Enrolled/target: 52/180 Collaborator/site: Chulalongkorn Hospital Funding: (KNIT) Knowledge Network Institute of Thailand T cells subsets in healthy children HIV-NAT 108 This is a cross-sectional study assessing the cellular subsets and immunoglobulins in healthy Thai children between the ages 2 and 15 years. This study will provide normal values of lymphocytes, monocytes, natural killer cells and immunoglobulins. Status: Enrollment closed Enrolled: 150 Collaborator/site: Chulalongkorn Hospital, Ramathibodi Hospital Funding: The Thailand Research Fund PIANO (TMC125-C213) HIV-NAT 112 This is a phase II, open-label multicentre trial evaluating the safety, tolerability and antiviral activity of Etravirine (TMC 125-C213) in treatment experienced HIV-infected children and adolescents. Status: Ongoing Enrolled: 5 Collaborator/site: Chulalongkorn Hospital Funding: Tibotec Pharmaceuticals Third line HAART in HIV-infected children HIV-NAT 113 This study will assess efficacy and safety of third line regimen in 150 Thai children. Status: Pending IRB approval Site PIs in Thailand: Kulkanya Chokephaibulkit,

Jurai Wongsawat, Rawiwan Hansudewechakul, Pope Kosalaraksa, Suparat Kanjanavanit, Chaiwat Ngampiyakul, Pakarat Sangkla Collaborators/sites: Chulalongkorn Hospital, Siriraj Hospital, Bamrasnaradura Institute, Chiang Rai Regional Hospital, Srinagarind Hospital Khon Kean University, Nakornping Hospital, Prapokklao Hospital & Surin Hospital Funding: Commission of Higher Education (CHE) MRI brain in Children HIV-NAT 121 This is a prospective study that will compare the total brain volume between HIV-infected and healthy children by using multimodal imaging approach such as tensor-based morphometry (TBM) and diffusion tensor imaging (DTI). Status: Pending IRB approval Collaborators/sites: HIV-NAT, SEARCH, Khon Kaen University, Chulalongkorn University, University of California at San Francisco,University of Missouri, University of California at Los Angeles Funding: National Institutes of Health

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PUBLICATIONS & WRITINGS

2009 has been a hectic year for hiv-nat with almost forty publications accepted in peer-reviewed journals, forty four presentations at conferences and twenty two grants submitted to national and international funding agencies. In 2009, the task for writing has mainly been with the seven physicians in the organizations. However, in this coming year, hiv-nat encourages non-physicians to lead and publish their own studies. journal

publications

impact factor

New England Journal of Medicine

1

50.017

Hepatology

1

11.355

Clinical Pharmacology & Therapeutics

1

7.586

Journal of Infectious Diseases

1

5.682

AIDS

7

5.640

Journal of Virology

1

5.308

Antimicrobial Agents and Chemotherapy

1

4.716

Journal of Acquired Immune Deficiency Syndromes

1

4.570

Journal of Antimicrobial Chemotherapy

2

4.328

Antiviral Therapy

3

4.105

Pediatric Infectious Disease Journal

2

3.176

Sexually Transmitted Infections

1

2.571

International Journal of Infectious Diseases

2

2.210

Hill A, van der Lugt J, Sawyer W, Boffito M. How much ritonavir is needed to boost protease inhibitors? Systematic review of 17 dose-ranging pharmacokinetics trials. AIDS (London, England) 2009; 23: 2237-45 van der Lugt J, Colbers A, Molto J, Hawkins D, van der Ende M, Vogel M, Wyen C, Schutz M, Koopmans P, Ruxrungtham K, Richter C, Burger D; SARA study team.The pharmacokinetic , safety and efficacy of boosted saquinavir tablets in HIV type-1-infected pregnant women. Antiviral therapy 2009; 14: 443-50 INSIGHT-ESPRIT Study Group; SILCAAT Scientific Committee, Abrams D, LĂŠvy Y, Losso MH, Babiker A, Collins G, Cooper DA, Darbyshire J, Emery S, Fox L, Gordin F, Lane HC, Lundgren JD, Mitsuyasu R, Neaton JD, Phillips A, Routy JP, Tambussi G, Wentworth D. Interleukin-2 therapy in patients with HIV infection. N Engl J Med 2009 Oct.15; 361(16):1548-59 Falster K, Choi JY, Donovan B, Duncombe C, Mulhall B, Sowden D, Zhou J, Law MG; on behalf of the Australian HIV Observational Database, the TREAT Asia HIV Observational Database. AIDS-related and non-AIDS-

related mortality in the Asia-Pacific region in the era of combination antiretroviral treatment. AIDS 2009 Nov.13; 23(17):2323-36 Bunupuradah T, Suntarattiwong P, Li A, Sirivichayakul S, Pancharoen C, Boonrak P, Puthanakit T, Kerr SJ, Ruxrungtham K, Chotpitayasunondh T, Hirschel B, Ananworanich J; the HIV-NAT 013 Study Team. Antiretroviral treatment outcome following genotyping in Thai children who failed dual nucleoside reverse transcriptase inhibitors. Int J Infect Dis 2009 Aug.20 Mills AM, Nelson M, Jayaweera D, Ruxrungtham K, Cassetti I, Girard PM, Workman C, Dierynck I, Sekar V, Abeele CV, Lavreys L. Once-daily darunavir/ritonavir vs. lopinavir/ritonavir in treatment-naive, HIV-1-infected patients: 96-week analysis. AIDS 2009 Aug. 24; 23(13):1679-88 Puthanakit T, van der Lugt J, Bunupuradah T, Ananworanich J, Gorowara M, Phasomsap C, Jupimai T, Boonrak P, Pancharoen C, Burger D, Ruxrungtham K. Pharmacokinetics and 48 week efficacy of low-dose lopinavir/ritonavir in HIV-infected children. J Antimicrob Chemother 2009 Nov. 64(5):1080-6

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Puthanakit T, Kerr S, Ananworanich J, Bunupuradah T, Boonrak P, Sirisanthana V. Pattern and predictors of immunologic recovery in human immunodeficiency virus-infected children receiving non-nucleoside reverse transcriptase inhibitor-based highly active antiretroviral therapy. Pediatr Infect Dis J 2009 Jun.; 28(6):488-92

Chang JJ, Sirivichayakul S, Avihingsanon A, Thompson AJ, Revill P, Iser D, Slavin J, Buranapraditkun S, Marks P, Matthews G, Cooper DA, Kent SJ, Cameron PU, Sasadeusz J, Desmond P, Locarnini S, Dore GJ, Ruxrungtham K, Lewin SR. Impaired quality of the HBV-specific T-cell response in HIV-1-HBV co-infection. J Virol 2009; 83(15):7649-58

Bunupuradah T, van der Lugt J, Kosalaraksa P, Engchanil C, Boonrak P, Puthanakit T, Mengthaisong T, Mahanontharit A, Lumbiganon P, Tompkins E, Burger D, Ruxrungtham K, Ananworanich J; HIVNAT 017 Study Team. Safety and efficacy of a double boosted protease inhibitor combination, saquinavir and lopinavir/ritonavir, in pretreated children at 96 weeks. Antivir Ther 2009; 14(2):241-8

Li AH, Phanuphak N, Sahasrabuddhe VV, Chaithongwongwatthana S, Vermund SH, Jenkins CA, Shepherd BE, Teeratakulpisarn N, van der LugtJ, Avihingsanon A, Ruxrungtham K, Shikuma C, Phanuphak P, Ananworanich J. Anal squamous intraepithelial lesions among HIV-positive and HIVnegative men who have sex with men in Thailand. Sex Transm Infect 2009 Jun. 11

van der Lugt J, Gorowara M, Avihingsanon A, Burger D, Ananworanich J, Sringam K, Kerr S, Wit F, Lange J and Ruxrungtham K. Reducing the boosting dose of ritonavir does not affect saquinavir levels in HIV-infected individuals. AIDS 2009; 23(9):11761179

Bunupuradah T, Puthanakit T, Pancharoen C, Butterworth O, Phanuphak P, Ananworanich J. Henoch-SchĂśnlein purpura and thrombocytopenia after planned antiretroviral treatment interruption in a Thai girl with HIV infection. Int J Infect Dis 2009 Jan.; 13(1):e31-3

Crane M, Oliver B, Matthews G, Avihingsanon A, Ubolyam S, Markovska V, Chang J, Dore GJ, Price P, Visvanathan K, French M, Ruxrungtham K and Lewin SR. Immunopathogenesis of hepatic flare in HIVHepatitis B Virus (HBV) co-infected individuals following initiation of HBV-active antiretroviral therapy. J Infect Dis 2009 Apr. 1; 199(7):974-981

NĂźesch R, Gayet-Ageron A, Chetchotisakd P, Prasithsirikul W, Kiertiburanakul S, Munsakul W, Raksakulkarn P, Tansuphasawasdikul S, Chautrakarn S, Ruxrungtham K, Hirschel B, Ananworanich J. and the STACCATO study group. The Impact of Combination Antiretroviral Therapy and its Interruption on Anxiety, Stress, Depression and Quality of Life in Thai Patients. Open AIDS Journal 2009; 3:38-45

Avihingsanon A, Van der Lugt J, Kerr SJ, Gorowara M, Chanmano S, Ohata P, Lange J, Cooper DA, Phanuphak P, Burger DM, Ruxrungtham K. A Low Dose of Ritonavir-Boosted Atazanavir (200/100 mg) Provides Adequate Pharmacokinetics Parameters in Thai HIV-1 Infected Adults. Clin Pharmacol Ther 2009; 85(4):402-8 Lewin SR, Ribeiro R, Avihingsanon A, Bowden S, Matthews G, Marks P, Locarnini SA, Ruxrungtham K, Perelson AS, Dore GJ. Viral dynamics of hepatitis B virus (HBV) in HIV-1-HBV co-infected individuals: similar anti-HBV efficacy of lamivudine, tenofovir or combination therapy Hepatology 2009; 49:1113-1121 Walmsley S, Avihingsanon A, Slim J, Ward D, Ruxrungtham K, Brunetta J, Bredeek UF, Jayaweera D, Guittari CJ, Larson P, Schutz M, Raffi F. Gemini: a non-inferiority study of saquinavir/ritonavir vs lopinavir/ ritonavir as initial HIV-1 therapy in adults. J Acquir Immune Defic Syndr 2009 Apr. 1; 50(4):367-74

Calmy A, Nguyen A, Montecucco F, Gayet-Ageron A, Burger F, Mach F, Carr A, Ubolyam S, Hirschel B and Ananworanich J for STACCATO study team. HIV activates markers of cardiovascular risk in a randomized scheduled-treatment interruption trial (STACCATO). AIDS 2009; 23(8):929-39 Puthanakit T, van der Lugt J, Bunupuradah T, Ananworanich J, Gorowara M, Phasomsap C, Jupimai T, Boonrak P,Pancharoen C, Burger D, Ruxrungtham K. Pharmacokinetics and 48 week efficacy of low-dose lopinavir/ritonavir in HIV infected children. J Antimicrob Chemother 2009 Nov.; 64(5):1080-6 Land S, Cunningham P, Zhou J, Frost K, Katzenstein D, Kantor R, Chen YM, Oka S, DeLong A, Sayer D, Smith J, Dax EM, Law M; TAQAS Laboratory Network. TREAT Asia Quality Assessment Scheme (TAQAS) to standardize the outcome of HIV genotypic resistance testing in a group of Asian laboratories. J Virol Methods 2009; 159:185-193


Puthanakit T, Chokephaibulkit K, Suntarattiwong P, Gorowara M, Vanprapar N, Leawsrisuk P, Suwanlerk T, Boonrak P, Ruxrungtham K. Therapeutic drug monitoring of lopinavir in HIV-infected children receiving generic lopinavir/ritonavir adult tablets. Pediatr Infect Dis J ( in press- Jan. 2010)

Kerr S and Phanuphak P. An Asian perspective on HIV/ AIDS. Asian Biomedicine 2009; 3(1): 9-14

Kerr SJ, Avihingsanon A, Pucharoen O, Chetchotisakd P, Ubolyam S, Ruxrungtham K, Cooper DA, Phanuphak P and Duncombe C. Assessing adherence in Thai patients taking HAART. Int J STD AIDS (In Press)

Hemachandra A and Duncombe C. New antiviral therapy and its role in HIV treatment in Asia. Asian Biomedicine. 2009; 3(1): 63-71.

Gibb DM, Green H, Compagnucci A, Klein N, Lallemant M, Lyall H, Nadal D, Ananworanich J, Babiker A, Bunupuradah T, Darbyshire J, De Rossi A. Response to Planned Treatment Interruptions in HIVinfection varies across Childhood in the PENTA 11 Trial. AIDS (In Press) Van Tieu H, Ananworanich J, Avihingsanon A, Apateerapong W, Sirivichayakul S, Klongutkara S, Boonchokchai B, Siangphoe U, Hammer S, Manosuthi W. Immunologic Markers as Predictors of Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome in HIV and TB Co-infected Persons in Thailand. AIDS Research and Human Retroviruses (In Press) Manosuthi W, Van Tieu H, Tantanathip P, Mankatitham W, Lueangniyomkul A, Ananworanich J, Anchalee Avihingsanon A, Siangphoe U, Klongugkara S, Thawornwan U, Suntisuklappon B, Sungkanuparph S, for the N2R Study Team. Clinical Case Definition and Manifestations of Paradoxical Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome. AIDS (In Press) van der Lugt J, Lange J, Avihingsanon A, Ananworanich J, Sealoo S, Burger D, Gorowara M, Phanuphak P, Ruxrungtham R. Plasma concentrations of generic lopinavir/ritonavir in HIV-1 infected individuals. Antiviral Therapy (In Press) Manosuthi W, Sungkanuparph S, Tantanathip P, Mankatitham W, Lueangniyomkul A, Thongyen S, Eampokarap B, Uttayamakul S, Suwanvattana P, Kaewsaard S, Ruxrungtham K; for the N2R Study Team. Body Weight Cutoff for Daily Dosage of Efavirenz and 60-week Efficacy of Efavirenz-based Regimen in Co-infected HIV and Tuberculosis Patients Receiving Rifampin. Antimicrob Agents Chemother 2009 Aug.10 REVIEW ARTICLES

Van der Lugt J and Avihingsanon A. Clinical pharmacology and pharmacokinetics of antiretrovirals in Asia. Asian Biomedicine 2009; 3(1): 53-62

Avihingsanon A, Hemachandra A & van der Lugt J. Antiretroviral therapy for HIV-associated tuberculosis. Asian Biomedicine. 2009; 3(1): 73-87. Puthanakit T and Bunupuradah T. Early versus deferred antiretroviral therapy in children in low and middle income countries. Current Opinion in HIV and AIDS (In press Jan. 2010) Sohn AH and Ananworanich J. Highly active antiretroviral therapy for children with treatment failure. HIV Therapy 2009; 3(5): 485-99 Duncombe C, Avihingsanon A, Hemachandra A, van der Lugt J, Ananworanich J, Ohata J, Puthanakit T, Bunupuradah T, Ruxrungtham K. The 12th Bangkok International Symposium on HIV Medicine. HIV Therapy 2009; 3(3): 225-8 Duncombe C, Ananworanich J, Phanuphak N, Vermund SH. Evidence-based Strategies for Preventing HIV Transmission and the Thailand Perspective. Asian Biomedicine 2009; 3(1):39-52 Bunupuradah T, Aurpibul L, Ananworanich J, Puthanakit T. The effectiveness of highly active antiretroviral therapy among HIV-infected children in Asian countries. Asian Biomedicine 2009; 3(1):89-100 Alter G, Ananworanich J, Pantophlet R, Rybicki EP, Buonaguro L. Report on the AIDS Vaccine 2008 Conference. Human Vaccine. 2009; Mar 8:5(3). Ruxrungtham K. HIV Immunology and Clinical Implications. In: Fundamental Global HIV Medicine. Mayo Clinic (In press) 2009

31


Presentations at conferences and meetings 32

In 2009, hiv-nat staff gave a total of twenty eight presentations at international conferences and meetings; three at the 16th Conference on Retroviruses and Opportunistic Infections (croi) in Montreal, Canada; six at the ias Conference on hiv Pathogenesis, Treatment and Prevention in Capetown, South Africa; and seven at the 1st International Workshop on hiv Pediatrics in Capetown, South Africa. 16th Conference on Retroviruses and Opportunistic Infections (CROI 2009). Montreal, Canada. February 8-11, 2009 Puls R, Hemachandra A, Sirivichayakul S, Kerr S, Thantiworasit P, Cooper D, Emery S, Kelleher A, Ruxrungtham K and the Australia Thai HIV Vaccine Consortium. A Randomised Phase I/IIa Trial of a Clade A/E DNA Prime, Recombinant Fowlpox Virus Boost HIV-1 Vaccine in a Low Risk Thai Population Puthanakit T, Jourdain G, Suntarattiwong P, Chokephaibulkit K, Siangphoe U, Sirisanthana V, Kosalaraksa P, Petdachai W, Hansudewechakul R, Ananworanich J on behalf of the HIV-NAT 086 study team. Efficacy data on double ritonavir-boosted protease Inhibitor-based HAART regimens in 137 children who had experienced virological failure on NNRTI-based treatment van der Lugt J, Gorowara M, Avingsanon A, Sringam K, Wit F, Intasan J, Ananworanich J, Phanuphak P, Burger D, Ruxrungtham K. A Boosting-Dose of 50 milligram of Ritonavir Generates Adequate Saquinavir Plasma Concentrations in Thai HIV-infected Patients 10th International Workshop on Clinical Pharmacology of HIV Therapy, April 15-17, 2009 Amsterdam, Netherlands van der Lugt J, Lange J, Avihingsanon A, Ananworanich J, Sealoo S, Burger D, Gorowara M, Phanuphak P, Ruxrungtham K. Bioavailability of generic lopinavir/ ritonavir in HIV-1 infected individuals [Abstract P-01] van der Lugt J, Iulio J di, Ananworanich J, Autar S, Ubolyam S, Siangphoe U, Jupimai T, Chetchotisakd P, Burger D, Ruxrungtham K, Hirschel B and the Staccato Thailand Study Group. Allelic variants of the CYP3A4 and 5, ABCB1 and SLCO1B1 Genes in a Thai HIV-infected Population on Saquinavir Based Antiretroviral Regimen

Gorowara M, Puthanakit T, Chokephaibulkit K, Suntarattiwong P, Vanprapar N, Leawsrisuk P, Suwanlerk T, Boonrak P, Ruxrungtham K. Therapeutic drug monitoring of lopinavir in HIV-infected children receiving generic lopinavir/ritonavir adult tablets van der Lugt J, Dekker LH, Heus SM, Burger D, Mootsikapun P, Kerr S, Gorowara M, Ruxrungtham K, Duncombe C. Pharmacokinetics of Low Dose Ritonavir in Combination with Different Protease Inhibitors in Thai HIV-1 infected Patients 7th International Workshop on HIV Cells of Macrophage/ Dendritic Lineage and Other Reservoirs. April 19-21, 2009, Colombaro di Corte Franca, Italy Valcour V, Shiramizu B, Ananworanich J, Shikuma C. HIV DNA in circulating CD14+ cells correlates to dementia in HAART-naive subjects 1st International Workshop on HIV Pediatrics, July 17-18, 2009, Cape Town, SOUTH AFRICA Kosalaraksa P, Bunupuradah T, Saphonn V, Puthanakit T, Wiangnon S, Luesomboon W, Lumbiganon P, Sopa B, Boonrak P, Chuenyam T,Cooper D, Ruxrungtham K and PREDICT study team. Prevalence and causes of anemia in HIV-infected children with moderate immune suppression in Thailand and Cambodia. Poster presentation Van der Lugt J, Saphonn V, Kosalaraksa P, Hansudewechakul R, Wongsawat J, Kanjanavanit S, Kerr S, Chuenyam T,Pruksakaew K, Ruxrungtham K, Puthanakit T on behalf of the PREDICT study group. Neurodevelopment and Behavioral Functioning in Antiretroviral-na誰ve Thai and Cambodian Children. Poster presentation


Bunupuradah B , Puthanakit T , Kosalaraksa P, Hansudewechakul R ,Kanjanavanit S Ngampiyasakul C , Wongsawat J , Luesomboon W, Saphonn V , Ananworanich J and on behalf of the PREDICT study group. Association of HIV immune suppression and quality of life among Thai and Cambodian antiretroviral therapy na誰ve HIV infected children. Poster presentation. Kanjanavanit S , Puthanakit T , Kosalaraksa P, Hansudewechakul R, Ngampiyaskul C, Wongsawat J , Luesomboon W, Saphonn V , Ananworanich J, Ruxrungtham K and on behalf of the PREDICT study group. High prevalence of lipid abnormalities among HIV-infected children with mild to moderate immunosuppression in Thailand and Cambodia. Oral presentation. Ananworanich J, Bunupuradah T, Ngampiyasakul C, Luesomboon W, Ubolyam S, Klangsinsirikul P, Gelman RS, Pattanapanyasat K, Saphonn V, Shearer WT, on behalf of the PREDICT study group. Peripheral blood T cell distributions in Thai and Cambodian children with HIV infection [Electronic Poster CDA 029]* Wongsawat J, Puthanakit T, Kanjanavanit S, Hansudewechakul R, Ngampiyasakul C, Kerr S, Ubolyam S, SuwanlerkT, Saphonn V, Ananworanich J. Sensitivity and Specificity of CD4 cell count to determine when to initiate ART according to the 2008 WHO guidelines [Abstract 1712]* Bunupuradah T, Lumbiganon P, Puthanakit T, Ananworanich J, Mengthaisong T, Boonrak P, Phanuphak P, Burger D, Pancharoen C, Kosalaraksa P. Simplifying antiretroviral treatment in virally suppressed children by switching from double boosted protease inhibitors to lopinavir/ritonavir monotherapy [Abstract 1449]* * These papers were also presented at the 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention

5th IAS Conference on HIV Pathogenesis, Treatment and Prevention. July 19-23 2009. Capetown, South Africa. Manosuthi W, Hong Van Tieu, Mankatitham W, Lueangniyomkul A, Ananworanich J, Avihingsanon A, Siangphoe U, Klongugkaraa S, Thawornwan U, Suntisuklappon B, Sungkanuparph S, for the N2R Study Team. Clinical Case Definition and Manifestations of Paradoxical Tuberculosis (TB) Immune Reconstitution Inflammatory Syndrome (IRIS)

Avihingsanon A, Van der Lugt J, Singphore U, Gorowara M, Phusadee K, Chanmano S, Boyd M, Phanuphak P, Burger D and Ruxrungtham K. Pharmacokinetics Safety and 24 weeks Efficacy of Ritonavir-Boosted Indinavir (600/100 mg BID) in HIV/ TB co-infected Thai patients receiving rifampin Khongphatthanayothin M, Avihingsanon A, Teeratakulpisarn N, Phanuphak N, Buajoom R and Phanuphak P. INH prophylaxis for TST-positive HIV clients at the Thai Red Cross AIDS Research Centre Avihingsanon A, Matthews GV, Lewin SR, Bowden S, Dore GJ and Ruxrungtham K. Tenofovir based HAART is associated with high rate of HBV DNA suppression, HBeAg, and HBs Ag seroconversion in Thai HIV/HBV coinfected patients Wongsawat J, Puthanakit T, Kanjanavanit S, Hansudewechakul R, Ngampiyasakul C, Kerr S, Ubolyam S, Suwanlerk T, Saphonn V, Ananworanich J. Sensitivity and Specificity of CD4 cell count to determine when to initiate ART according to the 2008 WHO guidelines. [Poster number WEPEB265] Falster K, Choi JY, Donovan B, Duncombe C, Mulhall B, Sowden D, Zhou J and Law M. on behalf of the Australian HIV Observational Database and the TREAT Asia HIV Observational Database. Mortality from AIDS and non-AIDS causes during combination antiretroviral treatment in high and low income settings in the Asia Pacific region. [Abstract number TUPEB099] 25th Anniversary International Conference for Pharmacoepidemiology and Therapeutic Risk Management. International Society for Pharmacoepidemiology (ISPE). Rhode Island, USA. August 16-19, 2009.

Kerr SJ, Sayer GP, Whicker SD, Rowett DS and Mant A. Survival analysis of Australian Vererans using COX-2 selective of non-selective NSAIDS. Pharmacoepidemiology and Drug Safety, 2009; 18: S206 Australiasian Society for HIV Medicine Conference, Brisbane September 9-11, 2009. Dazo C, Pussadee K, Srasuebkul P, Ananworanich J, Kerr S, Duncombe C, Puls RL, Emery S, Cooper DA for the Altair Study Group. Estimating glomerular filtration in patients from the ALTAIR study: comparison of Cockcroft-Gault and modification of diet in renal disease formulae

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34

International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 12th Annual European Congress. Paris, France. 24-27th October, 2009 Layton MR and Kerr SJ. Patient-healthcare provider communication: impact of patient satisfaction on the quality of health service 12th European AIDS Conference/EACS held in Cologne, Germany November 11-14, 2009. Avihingsanon A, Kerr S, , Komolmit P, Napissanant N, Mathews G, Dore G, Lewin S, Ruxrungtham K. Efficacy of tenofovir plus emtricitabine compared to emtricitabine based HAART in HIV/HBV Coinfected antiretroviral na誰ve individuals in Thailand: A Randomized Controlled Trial. Oral presentation AIDS Vaccine 2009, Paris, France 19-22 October 2009 Hemachandra A, Puls RL, Kerr SJ, Saengthong N, Pussadee K, Emery S, Phanuphak P & Ruxrungtham R. Wilingness to participate in a preventive HIV vaccine phase I/IIa trial in Bangkok, Thailand. [Abstract Number 162589] Sirivichayakul S, Felber BK, Pavlakis P, Buranapraditkun S, Thantiworasit P, Pitakpolrat P, Korber B, Ruxrungtham K. Pre-clinical immunogenicity of mosaic Asian HIV-1 DNA vaccine in mice HIV Immunology: From Infection to Immune Control, March 21-28 2009, Keystone Resort, Keystone, Colorado, USA Hempel U, Buranapraditkun S, Chatkulkawin P, Allgaier RL, Thantivorasi P, Pitakpolrat P, Battis LC, Lorenzen S, Sirivichayakul S, Hildebrand WH, Leitner T, Korber B, Goulder P, Matthews P, Altfeld M, Yu X, Brander C, Walker BD, Phanuphak P, Allen TM, Ruxrungtham K. Determining correlates of immune control in HIV-1 clade AE infection in the Thai population


35


HIV-NAT Research Laboratory

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hiv-nat research laboratory is a devision of aids, u.s., National Institutes of

Health-approved laboratory. It provides services to all hiv-nat clinical trials, especially studies funded by daids such as esprit (cpcra), stalwart (cpcra), start (cpcra) and predict (cipra). The hiv-nat research laboratory is enrolled in the National Health Security Organization Program for Bangkok, Thailand. In 2005, HIV-NAT Research Laboratory was assessed by DAIDS and was approved in January 2006. HIV-NAT Research Laboratory was reassessed annually in February 2007, 2008 and 2009. Many Laboratory Quality management and standards were developed according to DAIDS guidelines and as per the College of American Pathologists (CAP). HIV-NAT Research Laboratory was successfully accredited by The College of American Pathologists in April 2009. The HIV-NAT Research Laboratory is located on the 7th floor of the Research Building at Chulalongkorn University Hospital called Aor Por Ror Building which is 50 meters from the HIV-NAT main building. HIV-NAT lab serves as the central laboratory for the HIV-NAT study. The HIV-NAT laboratory facility comprises approximately 250 square metres of space. The laboratory has the capacity to perform diagnostic immuno-assays, cell phenotyping by flow cytometry, HIVRNA, DNA PCR, hepatitis and syphilis serology and molecular testing, haematology, chemistry and pharmacokinetics. The laboratory provides serum HIV and diagnostic serology testing for HIV, HBV and HCV, PCR for HIV proviral DNA, chlamydia, gonorrhea, and molecular quantitation of HIV by Cobas Ampliprep Amplicore (Roche), bDNA (Siemens). The laboratory also provides 2-, 3- and 4-color flow cytometry for T-cell phenotype analysis for adult and paediatric studies. Pharmacokinetics: HIV-NAT Research Laboratory has been conducting pharmacokinetic and therapeutic drug monitoring studies. HIV-NAT PK laboratory has provided services for other clinicians doing TDM for patient management. The TDM service is available for efavirenz, nevirapine and all protease inhibitors including Darunavir plus Tenofovir and Raltegravir. Our research studies focus on issues relevant to the Asian setting such as dose reduction of several ARVs and assess the quality of many generic products. Last year, the dose reduction of ritonavir, boosted atazanavir and lopinavir in children was studied. Another study will assess the bioavailability of generic lopinavir tablets which is ongoing and the results will be used by the Thai FDA. Many studies are in the pipeline and we will continue to gather more assays for future use. One of our future plans is to study anti-TB drugs such as Rifabutin. Our pharmacokinetic laboratory participates in an international quality control program and has met the standards required to conduct clinical work and high quality research which has been accredited by The College of American Pathologists in April 2009. Laboratory Network HIV-NAT laboratoryâ&#x20AC;&#x2122;s research has expanded its lab network for the following studies: Stalwart, START, and PREDICT (CIPRA) and HIV STAR. The communication between lab networks is done by laboratory teleconference every 2 months and requires site visit to conduct Laboratory Quality Monitoring which is done every year (full annual assessment)

Quality Management of Laboratory Network In January and February 2009, DAIDS conducted an Annual Laboratory assessment. The overall assessment of all sites indicated that everyone was compliant with GCLP practice and recommendations for improvement were provided to each site so they could reach the same level of international standard.


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HIV-NAT Laboratory Quality Manager conducted the PREDICT annual laboratory Quality management on the following dates: HIV-NAT: November 2009 Konkani: August 2009 Queen: July 2009 Bamras: October 2009 Chiangrai: November 2009 Nakornping: August 2009 Prapokklao: June 2009 HIV-NAT laboratory Manager also conducted the PREDICT annual laboratory Quality management at the National Laboratory Public Health, Pnompenh Cambodia on March, May, September, November 2009. Regular laboratory teleconferences with PREDICT lab coordinators are implemented every 2 months to discuss the problems related to laboratory issues that may affect the results of the PREDICT study. Also, we tracked their Proficiency Performance and outstanding Investigation Reports. CIPRA Laboratories under the CIPRA program received valuable tips from DAIDS on how to improve quality management system and how to reach level of international standards.

Staff Laboratory Director: Prof. Kiat Ruxrungtham Laboratory Manager: Sasiwimol Ubolyam Laboratory Quality Manager: Apicha Mahanontharit Total number of staff is 14: 7 Laboratory Medical Technologists, 1 Scientist, 1 Pharmacologist, 1 Senior Laboratory assistant, 2 laboratory assistants and 1 lab Clerk and 1 part time Medical Technologist AuditorS Phillip Cunningham, Senior Operations Manager, St.Vincentâ&#x20AC;&#x2122;s hospital, Australia Mike Ussery, Division of AIDS, NIH, USA Neal Wetherall, Division of AIDS, NIH, USA


THE VACCINE AND CELLULAR IMMUNOLOGY LABORATORY

Chulalongkorn University Medical Research Centre (CHULA-MRC)

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Research projects 1 Mosaic HIV-1 Clade A/E/B humanized gag, pol and nef DNA vaccinE: R&D Following previous report that our mosaic HIV DNA constructs (in pCMVkan) which are representative of several HIV sequences (156 CRF01_AE and 72 Asian HIV subtype B) have been shown to induce broader immune responses against various clades. We then compared the immunogenicity of mosaic HIV DNA constructs again by intradermal (ID) and needle-free injector (NF) using 100 and 50 µg, respectively, of the 3 mosaic-gag mixtures. The vaccinations were performed on days 0, 14 and 28. An additional group received 5-million pfu vaccinia-AE boost on day 42. All mice showed anti-p24 antibody responses of at least 1 : 10,000. For ELISpot assay, with the AE-peptide pool stimulation, the responses (median spots (range)) were 430 (291-643) and 953 (641-1206) SFC/million splenocytes for ID and NF groups, respectively. Whereas with the B-peptide pool stimulation, the responses were 560 (411-776) and 1151 (711-1352) for the ID and NF groups, respectively. The NF group showed statistically higher cellular immune responses testing with either peptide pools (p = 0.0043 for AE & B, Mann-Whitney test). The prime/boost strategy using AE vaccinia virus gave much better responses of 1756(1062-2293) when stimulated with the AE-pool (p = 0.0087) but no increase in B-peptide responses (930 spots (679-1270)). 2 HLA typing and epitope mapping relative to HIV vaccine design This project is in collaboration with Professor Bruce Walker and Todd M. Allen, Partners AIDS Research Center, Massachusetts General Hospital, Boston, MA, USA, funded by the NIH (NIAID Contract No. N01-AI-30024). The purpose of this project is to study cells (T and B cells) involved in immune responses to HIV-1 in order to better understand the mechanisms of the responses and to enhance vaccine design and development. The study aims to enrol 250 anti-retroviral naïve, HIV-infected and 150 HIV sero-negative individuals. The samples will be collected for HLA typing, sequencing for HIV-1 gag/env/nef genes and cell-mediated immune responses, especially CD4+ and CD8+ T cells, to the virus. Forty novel CTL epitopes have been identified based on ELISpot and HLA typing data. Mapping of CD4 T cell epitopes has been initiated in 15 subjects. CD4 T cell lines were shipped to Boston for fine mapping. Over 40 promising CD4 T cell responses were identified. Gag and Nef sequences, both full-length and partial are completed from 95 subjects. Currently we are working on two publications. The first one is “a comprehensive analysis of CD8 and CD4 responses in the Thai population” and the second one is “the fine mapping of a novel immunodominant C0102 –YI-9 epitope escaping in the Thai population”. The abstract generated from this project was presented at Keystone, Colorado, USA (Abstract 1). 3 HIV Resistance CTL Epitope Mapping This project is to study HIV reverse transcriptase (RT) and protease (Pr) epitopes that can induce the CTL responses in antiretroviral (ARV) -naïve and ARV-experienced Thai patients. This project is supported by the National Center for Genetic Engineering and Biotechnology (BIOTEC) grant. The Purpose of this study is to study the frequency and magnitude of CTL responses against HIV-1 CRF01_AE pol protein, (both wild type and mutant proteins) in antiretroviral (ARV) -naïve, ARV treatment success and ARV treatment failure (with drug resistant virus) individuals. Up to September 2008, 94 HIV-infected volunteers have been enrolled, 39 ARV naïve and 55 ARV experienced. A panel of truncated peptides of PR and RT, both WT and mutant (MT), were used to test HIV specific T cell responses by ELISpot assay. Ten novel CTL epitopes have been identified based on ELISpot and HLA typing data.


PUBLICATIONS 1 Land S, Cunningham P, Zhou J, Frost K, Katzenstein D, Kantor R, Chen YM, Oka S, DeLong A, Sayer D, Smith J, Dax EM, Law M; TAQAS Laboratory Network. TREAT Asia Quality Assessment Scheme (TAQAS) to standardize the outcome of HIV genotypic resistance testing in a group of Asian laboratories. J Virol Methods 2009; 159: 185-193 2 Chang JJ, Sirivichayakul S, Avihingsanon A, Thompson AJ, Revill P, Iser D, Slavin J, Buranapraditkun S, Marks P, Matthews G, Cooper DA, Kent SJ, Cameron PU, Sasadeusz J, Desmond P, Locarnini S, Dore GJ, Ruxrungtham K, Lewin SR. Impaired quality of the HBV-specific T-cell response in HIV-1-HBV co-infection. J Virol 2009; 83: 7649-7658 3 Bunupuradah T, Suntarattiwong P, Li A, Sirivichayakul S, Pancharoen C, Boonrak P, Puthanakit T, Kerr SJ, Ruxrungtham K, Chotpitayasunondh T, Hirschel B, Ananworanich J; the HIV-NAT 013 Study Team. Antiretroviral treatment outcome following genotyping in Thai children who failed dual nucleoside reverse transcriptase inhibitors. Int J Infect Dis 2009 ABSTRACT AIDS Vaccine 2009, October 19-22, Paris, France Pre-clinical immunogenicity of mosaic Asian AE/B HIV-1 DNA vaccine in mice Sirivichayakul S 1, Felber BK 2, Kulkarni V 2, Pavlakis GN 3, Buranapraditkun S 1, Thantiworasit P 1, Pitakpolrat P 1, Allen T 4, Leitner T 5,Korber B 5, Ruxrungtham K 1 1 Vaccine and Cellular Immunology (VCI) Laboratory, Chulalongkorn Medical Research Center (Chula MRC), Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand | 2 Human Retrovirus Pathogenesis Section and 3 Human Retrovirus Section, National Cancer Institute at Frederick, MD, USA and 4 Partners AIDS Research Center, Harvard Medical School, MA, USA and 5 LANL, New Mexico, USA

BACKGROUND To cover the genetic diversity of HIV-1 among Asian countries, three mosaic HIV-1 DNA vaccines encompassing the gag gene derived from HIV-1 CRF01_AE and Asian HIV-1 subtype B were constructed and tested for immunogenicity in Balb/c mice. Methods: Full-length gag sequences of 1.5 kb derived from 156 CRF01_AE and 72 Asian HIV-1 subtype B were computerized to generate 3 representative mosaic Asian HIV-1 gag genes. The mosaic gag genes were RNA-optimized and cloned into pCMVkan expression vector. Mice were immunized by intradermal (ID) and needlefree injector (NF) using 100 and 50 Âľg, respectively, of the 3 mosaic-gag mixtures. The vaccinations were performed on days 0, 14 and 28. An additional group received 5-million pfu vaccinia-AE boost on day 42. Mice were sacrificed on day 35 (DNA alone) and day 49 (DNA prime/vaccinia boost) and the immunogenicity was assessed by anti-p24 antibody and IFN-gamma ELISpot assays. Both HIV-1 AE- and B-peptide pools were used separately to stimulate splenocytes. RESULTS All mice showed anti-p24 antibody responses of at least 1 : 10,000. For ELISpot assay, with the AE-peptide pool stimulation, the responses (median spots (range)) were 430 (291-643) and 953 (641-1206) for ID and NF groups, respectively. Whereas with the B-peptide pool stimulation, the responses were 560 (411-776) and 1151 (711-1352) for the ID and NF groups, respectively. The NF group showed statistically higher cellular immune responses testing either peptide pools (p = 0.0043 for AE & B, Mann-Whitney test). The prime/boost strategy using AE vaccinia virus gave much better responses of 1756(1062-2293) when stimulated with the AE-pool (p = 0.0087) but no increase in B-peptide responses (930 spots (679-1270)). Conclusion: Our results suggest that the mosaic Asian HIV-1 DNA vaccine was immunogenic and could induce both humoral- and cell-mediated immune responses with appropriate immunization modification, i.e., using NF and prime/boost strategies.

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ABSTRACT HIV Immunology: From Infection to Immune Control, March 21-28 2009, Keystone Resort, Keystone, Colorado, USA Determining correlates of immune control in HIV-1 clade AE infection in the Thai population Ursula Hempel 1, Supranee Buranapraditkun 2, Pornsupa Chatkulkawin 2, Rachel L. Allgaier 1, Pattarawat Thantivorasit 2, Patrawadee Pitakpolrat 2, Laura C. Battis 1, Sven-Iver Lorenzen 2, Sunee Sirivichayakul 2, William H. Hildebrand 3, Thomas Leitner 4, Bette Korber 4, Philip Goulder 5,6, Philippa Matthews 5, Marcus Altfeld 1, Xu Yu 1, Christian Brander 1, Bruce D. Walker 1, Praphan Phanuphak 2, Todd M. Allen 1, Kiat Ruxrungtham 2 1 Ragon Institute of Harvard and MIT (formerly Partners AIDS Research Center) Boston, MA, USA | 2 Vaccine and Cellular Immunology Laboratory, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand | 3 Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, USA | 4 Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM, USA | 5 Department of Paediatrics, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom | 6 HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa

To date little is known about clade CRF01_AE HIV infection which dominates in South and Southeast Asia. Since a successful HIV vaccine will likely need to be clade specific, it is important to identify correlates of immune control in clade AE infection. We have screened a cohort of 250 chronically HIV infected (HAART na誰ve) patients in Bangkok, Thailand. Epidemiological data, viral load and CD4 cell count were collected, and genome wide IFN-g ELISpot responses were determined in 188 clade AE infected subjects. The strongest and most frequent CD8 responses targeted Nef, Pol and Gag (particularly p24). While total CD8 responses did not show an effect on viral load, Gag-specific responses, in particular p24, did correlate with immune control, while responses against Pol, Nef, and Env exhibited no effect. HLA alleles -A2402, -A3001, -A2410, -B1302, -B2704/06, and -Cw0801 also correlated with viral control and CD4 count preservation, however only -B1302 reached statistical significance (p=0.0287). We have now mapped 16 novel optimal CD8 epitopes across the viral genome and are in the process of fine mapping additional epitopes. These data begin to provide important insights and tools to determine the correlates of immune control in clade AE infection. This study was supported by NIH Contract N01-A1-30024.


Education and Development Program hiv-nat’s medical, laboratory, biostatistics and study coordinator staff have

provided several trainings for doctors, nurses and medical technologists ranging from hiv and opportunistic infections, clinical trial registries, laboratory to biostatistics courses. Our staffs’ knowledge and skills are highly sought by universities, professional organizations, hospitals, governmental organizations and other ngo’s. Our doctors provide refresher courses to nurses at hospitals and university hospitals throughout Thailand as well as up-to-date information on hiv for doctors both regionally and nationally. Our laboratory staffs offer training regionally and nationally, and monitor the laboratories for qc/qa. Our biostatistician has provided lectures targeting young investigators at large, well-known organizations such as Treat Asia. hiv-nat physicians also mentor Thai and International doctors and phd candidates. SEARCH Regional HIV/AIDS Training Bangkok, Thailand January 11-21, 2008 The 8th National Conference on Thailand towards Center of Excellence in Clinical Trials “Healthy and powerful infrastructures for clinical researches in Thailand” August 14-15, 2008 SEARCH Regional HIV/AIDS Training for Vietnamese physicians Bangkok, Thailand September 9-23, 2008 Thai Red Cross AIDS Research Centre Training Course May 30-June 6, 2008 Thai Red Cross AIDS Research Centre Training Course September 1-19, 2008 International Bangkok Conference, Thailand 14 January, 2009 HIV/AIDS Training on Adult HIV Treatment for TREAT Asia, Bangkok, Thailand January 21, 2009 Standard Course in Clinical Trials at the Chulalongkorn University, Chulalongkorn Memorial Hospital, Bangkok, Thailand March 30 - April 1, 2009 SEARCH Regional HIV/AIDS Training for Vietnamese physicians, Bangkok, Thailand April 20-30, 2009

5th HIV Drug Resistance Workshop: Basic Principles & Clinical Implications May 11-12, 2009 National AIDS Meeting 2009 May 27-29, 2009 TREAT Asia Resistance Data Management and Biostatistics Training Workshop June 24-25, 2009 SEARCH Regional HIV/AIDS Training for Bangladesh physicians, Bangkok, Thailand June 26-July 3, 2009 Annual Study coordinators and CRAs Training 2009 August 1, 2009 Chulalongkorn Faculty of Nursing HIV Training 2009 August 17-18, 2009 The 9th Thailand Towards Excellence in Clinical Trials Forum 2009: Time to Act at the Chulalongkorn University, Chulalongkorn Memorial Hospital, Bangkok, Thailand August 20 - 21, 2009 HIV[e]Education Computer Based Learning Course Workshop, Bangkok, Thailand September 3-4, 2009 Update in HIV Management 2009 (sponsored by Abbott) September 19, 2009

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SEARCH Regional HIV/AIDS Training Bangkok, Thailand January 11-21, 2008 The 8th National Conference on Thailand towards Center of Excellence in Clinical Trials “Healthy and powerful infrastructures for clinical researches in Thailand” August 14-15, 2008 SEARCH Regional HIV/AIDS Training for Vietnamese physicians Bangkok, Thailand September 9-23, 2008 Thai Red Cross AIDS Research Centre Training Course May 30-June 6, 2008 Thai Red Cross AIDS Research Centre Training Course September 1-19, 2008 International Bangkok Conference, Thailand 14 January, 2009 HIV/AIDS Training on Adult HIV Treatment for TREAT Asia, Bangkok, Thailand January 21, 2009 Standard Course in Clinical Trials at the Chulalongkorn University, Chulalongkorn Memorial Hospital, Bangkok, Thailand March 30 - April 1, 2009 SEARCH Regional HIV/AIDS Training for Vietnamese physicians, Bangkok, Thailand April 20-30, 2009 5th HIV Drug Resistance Workshop: Basic Principles & Clinical Implications May 11-12, 2009

The 9th Thailand Towards Excellence in Clinical Trials Forum 2009: Time to Act at the Chulalongkorn University, Chulalongkorn Memorial Hospital, Bangkok, Thailand August 20 - 21, 2009 HIV[e]Education Computer Based Learning Course Workshop, Bangkok, Thailand September 3-4, 2009 Update in HIV Management 2009 (sponsored by Abbott) September 19, 2009 Capacity Building for the Ethical Review Committee of Health Sciences September 19-22, 2009 TREAT Asia Network Meeting 2009 October 11, 2009 Staff Training in Laboratory Quality Assurance Laboratory quality improvement training was provided sometime during 2009.

Assessment of impact of training effort by summary of laboratory performance 1 Assessment of knowledge and skills in standards for Test, Quality Control and Verification of Performance Specifications by audit findings related item of Verification of Performance Specifications from Annual DAIDS Laboratory Assessment and Annual PREDICT Laboratory Assessment by HIV-NAT Laboratory Manager and Quality Manager The findings from the audit showed that after a year of training, there was a gradual reduction of violations.

National AIDS Meeting 2009 May 27-29, 2009 TREAT Asia Resistance Data Management and Biostatistics Training Workshop June 24-25, 2009 SEARCH Regional HIV/AIDS Training for Bangladesh physicians, Bangkok, Thailand June 26-July 3, 2009 Annual Study coordinators and CRAs Training 2009 August 1, 2009 Chulalongkorn Faculty of Nursing HIV Training 2009 August 17-18, 2009

2 Assessment of knowledge and increased skill of in-house laboratory equipment calibration by audit findings related item of Equipment from Annual DAIDS Laboratory Assessment and Annual PREDICT Laboratory Assessment by HIV-NAT Laboratory Manager and Quality Manager • The findings from the audit showed that after a year of training, there was a gradual reduction of violations. • Sites can develop in- house calibration for critical equipments such as Balance, Water bath, Centrifuge, Autopipette and Thermometer. These equipments need to be calibrated and maintained according to DAIDS guideline. We also set up a network among


PREDICT study sites to accommodate calibration and reduce the burden cost of equipment calibration. • In house Laboratory Equipment Calibration Skills increased (By Questionnaires) Balance and Standard weight Water bath Thermometer Autopipette Centrifuge

100% 80% 92% 83% 86%

3 Assessment of Compliance with GCLP standards There are no major Incompliance GCLP standards that was reported by DAIDS Laboratory assessment for the year 2009 for every site and the Annual PREDICT Laboratory Assessment by HIV-NAT Laboratory Manager and Quality Manager. In addition, HIV-NAT Research Laboratory which is the laboratory Center for training grant management has fulfill GCLP standards and was accredited by The College of American Pathologist (CAP) on April 2009 4 Assessment of Lower rate of Proficiency Testing Failure 5 Assessment of Submitting Investigation report (corrective action) of PT failure in a timely manner. In general, all trainings were successful and the outcome measurements indicated that everyone was serious in rectifying the problems. In addition, continuous training for Laboratory Quality Assurance is the main reason why Clinical Laboratories participating in International Clinical trials are successful. HIV-NAT Research Laboratory Manager has provided a lecture on, “Common Pitfalls in GLP” for the Workshop in Standard Course for Clinical trials, Faculty of Medicine Chulalongkorn University on March 2009. HIV-NAT Research Laboratory Manager has provided GCLP training for participants from Bangladesh as part of the SEARCH Regional HIV/AIDS training which was held on April 2009. HIV-NAT Research Laboratory Manager has provided GCLP principle training for Vietnamese participants as part of the SEARCH Regional HIV/AIDS training which was held on September 2008.

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The Bangkok International Symposium on HIV Medicine 44

The Bangkok International Symposium on hiv Medicine is a key component of, the Netherlands, Australia, Thailand Research Collaborationâ&#x20AC;&#x2122;s (hiv-nat) commitment to training and education. It has been convened by hiv-nat each January for the past 13 years and at the Queen Sirikit National Convention Centre in Bangkok since 1999.

The 13th Symposium will be conducted at: The Queen Sirikit National Convention Centre January 20-22, 2010 The objectives of the three day symposium are to provide physicians, health care workers and members of the HIV-infected and affected community from Thailand and countries in the region with a comprehensive review of the management of HIV infection and opportunistic infections, the latest updates on research into HIV treatments and vaccines and efforts to improve access to therapy. World class international and local speakers present plenary sessions and facilitate interactive workshops. In 2009, more than 700 participants from eleven countries (Thailand, Laos, Myanmar, Vietnam, Cambodia, Indonesia, India, Singapore, Taiwan, China and Korea) attended the symposium. The Bangkok Symposium on HIV Medicine is the largest meeting of its kind in Asia.


HIV-NAT PERSONNEL

Medical Department

Left to right Hathairat Kanganaboonmalert Wasana Prasitsuebsai Thanyawee Puthanakit Kiat Ruxrungtham Anchalee Avihingsano Nadia Kancheva Landolt Reshmie Ramautarsing Somporn Chantbuddiwet Pirapon June Ohata

Praphan Phanuphak, Jintanat Ananworanich, Chris Duncombe & Torsak Bunupuradah

Clinical Trials Nursing Department

Left to right Augchara Suwannawut Tawan Mengthaisong Suchat Thamsala Bussara Krasaeboot Chayapa Phasomsap Supalak Klungklang Wanida Thiansanguanku Walaiporn Wongngam

Clinical Trials Nursing Department

Left to right Chuleeporn Khongpetch Jaruwan Sarachat Siriporn Saeloo Supaporn Pengsuma Thanaporn Mansawat Nounpen Saengthong Nithima Panyanithisakul

Apirudee Panthong

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Clinical Trials Coordination Department

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Left to right Thidarat Jupimai Kanchana Pruksakaew Kanitta Phusadee Tulathip Suwanlerk

Laboratory Department

Front row (L-R) Sasiwimol Ubolyam Tanyathip Jaimulwong Back row (L-R) Thitirat Detchaiyasak Ponlakrit Khamrin Phantipa Onsam-ang Patcharin Eamyoung Naphassanant Laopraynak Apicha Mahanontharit

Laboratory Department

Left to right Bunruan Sopa Umaporn Chobkarching Phonethipsavanh Nouanthong Thitiporn Somjit Patcharee Pararit Kannika Khlungklang Channuwat Bouko


Pharmacy Department 47

Left to right Parinya Sutheerasak Threepol Sattong Plengsri Lertarom Ratree Longcharoen Niti Wongthai Anuntaya Uanithirat Sarapol Tongphan

Chulalak Sriheara

IT and Data Management Department

Front row (L-R): Chavalun Ruengpanyathip Wanchai Thongsee Orathai Chaiya Ormrudee Rit-im and Chowalit Phadungphon Back row (L-R): Boonjit Deeaeim Wichai Changyencham Theeradej Boonmangam Ekkasit Todsanit

Statistical Department

Left to right Tanakorn Apornpong Pitch Boonrak Jiratchaya Wongsabut

Stephen Kerr


Clinical Trials Monitoring Department

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Left to right Primwichaya Intakan Sirikul Chanmano Praneet Pinklow Kobkeaw Laohajinda Sineenart Chautrakarn Jintana Intasan & Peeraporn Kaew-on

Quality Management & Regulatory Department

Left to right Chatsuda Auchieng Kanokon Sirichumpa

Gunyanee Sattong

Department of Financial Services

Left to right Umaporn Methanggool Chornarin Thangjitthanom Kesdao Nanthapisal Duangmanee Seedam


Department of Administration and Human Resources

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Left to right Yodying Kittimakorn Sommai Sattong Ruksina Chumchure Jeerakan Janhom Natthapa Pitayanon Adisak Jamrasrak

SEARCH PERSONNEL SEARCH Project

Left to right Sudrak Lakhonpon Suriya Kongkuan Pairoa Praihirunkit Varaporn Pothipala Thep Chalermchai Somprartthana Ratanamanee Duanghathai Suttichom Nitiya Chomchey Jintanat Ananworanich Nittaya Phanuphak Sangla Najai


TRC-ARC PERSONNEL Special Task Force Team

Left to right Jureeporn Jantarapakde Khonchaya Kunacheeva Nittaya Phanuphak Rosalin Kriengsinyat Chintana Chaturawit Somsong Teeratakulpisarn Warabhorn Pima Chayaporn Tasai Waraporn Sirisakyot

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Special Task Force Team

Left to right Jureeporn Jantarapakde Khonchaya Kunacheeva Nittaya Phanuphak Rosalin Kriengsinyat Chintana Chaturawit Somsong Teeratakulpisarn Warabhorn Pima Chayaporn Tasai Waraporn Sirisakyot

Thai Red Cross AIDS Research Center Administrative Department

Front row (L-R) Vijitra Pradubkaew, Nion Kusalinkul, Supawadee Wongnornoi, Somchart ThaKaeng & Patinya Suriwong Back row (L-R) Sukanya Kaivikaikosol, Ruethairat Pruksasri, Sumitra Techapalokul, Taweesup Deesua, Songsri Wiriyawong, Sunanta Intarasuk & Mongkol Mukkapun Missing: Kalayaporn Panthawong, Thanachai Ludkrood, Anannet Thienhorm, Adisak Chaipunna, Charnwit Pakam, Rudda Pannun, Siripen Areeprayunkit, Orawan Panichob, Somchai Wuthiworakul & Somjai Kokapant


PARTNERSHIPS

MOPH Ministry of Public Health (MOPH) Thailand provides policy direction through membership of the HIV-NAT international advisory board, approval for the importation of study materials and assistance with the provision of study medications. The Foundation for AIDS Research (amfAR) Establishment of the amfAR Office in Bangkok, Thailand The amfAR office in Thailand was established with the successful completion of the application to the Ministry of Labor in April of 2006. As reported in the application, this office is intended to support the regional efforts of the TREAT Asia (Therapeutics Research, Education and AIDS Training in Asia) program (http://www.amfar.org/ treatasia). The program was launched in July 2001 and is intended to provide support for the safe and effective delivery of HIV treatments in Asia. The program is currently supporting projects in 16 economic regions around Asia including Cambodia, China, India, Indonesia, Hong Kong, Japan, Laos, Malaysia, Papua New Guinea, the Philippines, Singapore, South Korea, Taiwan, Thailand, Viet Nam and Australia. The projects focus on four primary objectives: research, education and training, public policy and communications, and strengthening civil society through treatment education and treatment literacy. The program currently employs 19 staff members. TAHOD: The TREAT Asia HIV Observational Database (TAHOD) is a collaborative observational cohort study, which involves 19 participating sites in the Asia and Pacific region including HIV-NAT/Thai Red Cross (Bangkok), Ramathibodi Hospital (Bangkok) and Chiang Mai University - Research Institute for Health Science (Chiang Mai). The primary objectives of the TREAT Asia HIV Observational Database are to: 1 Develop capacity in HIV clinical data collection in countries of the Asia Pacific region 2 Assist in evaluation of new HIV treatments for the Asia-Pacific region 3 Monitor anti-retroviral and prophylactic treatment as related to demographics and markers of HIV disease stage 4 Monitor toxicity to anti-retroviral therapy 5 Examine HIV natural history, including the relationship between access to antiretroviral therapy and disease progression The project was established in 2003 and has, as of the latest data transfer (March 2009), enrolled 4,400 patients into prospective follow-up. The program is supported in part by a grant from the US National Institutes of Health and the Ministry of Foreign Affairs of the Netherlands. TASER: The TREAT Asia Studies to Evaluate Resistance (TASER) for HIV-1 Genotypic Anti-Retroviral Drug Testing TASER is a comprehensive program to evaluate HIV drug resistance within TREAT Asia clinical centers and to build capacity for HIV genotypic antiretroviral (ARV) resistance testing (genotyping), surveillance of transmission of ARV resistant HIV, and monitoring the development ARV resistant HIV in persons taking ARV therapy. Currently, there are 16 participating sites in 5 countries in the Asia region, including HIV-NAT/Thai Red Cross (Bangkok), Ramathibodi Hospital (Bangkok), Siriraj Hospital (Bangkok), Chiang Rai University and Chiang Mai University. Standardization of genotyping through the TREAT Asia Quality Assessment Scheme (TAQAS) forms an integral part of this program.

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TAQAS: the TREAT Asia Quality Assurance Scheme TAQAS is designed to build capacity for and establish external quality assurance for HIV drug-resistance testing. Proficiency panels include HIV samples derived from HIV-1 subtype B and non-B isolates endemic in the South, East, and Southeast Asia. TAQAS laboratories support HIVDR testing for the TASER clinical studies. In April 2006, TAQAS was first implemented in 9 Southeast Asian laboratories. Now, there are 24 participating sites from 15 countries in the Asia-Pacific region, Africa and America, including 4 laboratories in Thailand: Chulalongkorn University (Bangkok), Ramathibodi Hospital (Bangkok), Siriraj Hospital (Bangkok) and Chiang Mai University (Chiang Mai). HIV-1 subtype B and non-B isolates endemic in the South, East, and Southeast Asia. TAQAS laboratories support HIVDR testing for the TASER clinical studies. In April 2006, TAQAS was first implemented in 9 Southeast Asian laboratories. Now, there are 24 participating sites from 15 countries in the Asia-Pacific region, Africa and America, including 4 laboratories in Thailand: Chulalongkorn University (Bangkok), Ramathibodi Hospital (Bangkok), Siriraj Hospital (Bangkok) and Chiang Mai University (Chiang Mai). TApHOD: The TREAT Asia Pediatric HIV Observational Database TApHOD is a collaborative observational cohort study, which involves 12 participating sites 5 countries in the Asia and Pacific region including HIV-NAT/Thai Red Cross (Bangkok), Siriraj Hospital (Bangkok), Chiang Mai University - Research Institute for Health Science (Chiang Mai), Chiang Rai Regional Hospital (Chiang Rai), and Khon Kaen University (Khon Kaen).The primary objectives of the TREAT Asia Pediatric HIV Observational Database are to: 1 Develop capacity in HIV clinical data collection in countries of the Asia Pacific region 2 Assist in evaluation of new pediatric HIV treatments for the Asia-Pacific region 3 Monitor anti-retroviral and prophylactic treatment as related to demographics and markers of HIV disease stage 4 Monitor toxicity to anti-retroviral therapy. 5 Examine HIV natural history in children, including the relationship between access to antiretroviral therapy and disease progression The project was established in 2006 and has, as of the latest data transfer (March 2009), enrolled 2,535 patients into prospective follow-up. The program is supported in part by a grant from the U.S. National Institutes of Health, U.S. National Institute of Child Health and Human Development and the Austrian AIDS Life Association. Education and Training Education Program for Building Research Capacity TREAT Asia implemented a research capacity-building education program with support from the Australian Agency for International Development (AusAID) in 2008. The program will include research capacity site assessments, in-country trainings on good clinical research practices, and provision of technical assistance awards in Cambodia, China, Indonesia, Papua New Guinea, the Philippines and Vietnam. Training programs will utilize experts from the TREAT Asia network, as well as from the National Centre in Epidemiology and Clinical Research (NCHECR) at the University of New South Wales in Sydney, and other international academic centers. Policy and Communications The TREAT Asia Report includes reviews of current research activities in the TREAT Asia network and elsewherein Asia and the Pacific. The Report has featured interviews with leading figures in AIDS treatment, research, and policy. It is produced on a quarterly basis as part of TREAT Asiaâ&#x20AC;&#x2122;s communications activities. Strengthening Civil Society To strengthen civil society and community involvement in HIV/AIDS programs in the Asia-Pacific region, TREAT Asia supports activities to provide HIV treatment literacy training, develop community advocacy, and coordinate a network of men-who-havesex-with-men (MSM) organizations.


Regional Coordinating Secretariat for the Purple Sky Network of MSM Programs in the Greater Mekong Sub-region TREAT Asia serves as the Regional Coordination Secretariat (RCS) for the Purple Sky Network, a network of organizations working on HIV issues related to Men-Whohave- Sex-with-Men in the Greater Mekong Sub-region (GMS). The purpose of the RCS is to provide support, facilitate network communications and activities, monitor progress and represent the network in the international arena. Global Fund to fight AIDS, Tuberculosis and Malaria This program started in 2006 with the aim to use the Global Fund money to buy antiretroviral therapy and monitoring assays for monitoring CD4 and viral load for patients post clinical trials. HARRT has been shown to effectively reduce HIV related illnesses and mortalities. It does improve our patientsâ&#x20AC;&#x2122; quality of lives significantly. Besides providing ARV therapy to patients, we also collect long term data from each patient participating in the study. ARV drugs, CD4 and viral load tests are supported by Global Fund. Currently, 522 adults and 84 children receive free ARV drugs. 1078 adults and 193 children receive free CD4 and viral load tests.Because of the outstanding outcome of this yearâ&#x20AC;&#x2122;s program, we are currently proposing to Global Fund to continue the program via the rolling continuation channel. Service Praphan Phanuphak is a member of the Governing Council of the International AIDS Society (IAS), representing the Asia-Pacific Region, a member of WHO HIV Treatment Guidelines and WHO HIV Resistance Network Committees. He is also a member of the HIV Governance Group of the International Federation of Red Cross Red Crescent Societies (IFRC). He is the member of Thailand National AIDS Committee and the Vice-Chair of Thailand Country Coordinating Mechanism (CCM) of Global Fund for AIDS, Tuberculosis and Malaria. He is the Vice-Chair of Thailand 2010 HIV Treatment Guidelines. Kiat Ruxrungtham is a member of the expert panel working group of the Thai Ministry of Public Heath HIV/AIDS management guidelines, a member of the expert panel working group on antiretroviral therapy practice policy guidelines, a member of the National AIDS Committee chaired by the Prime Minister, the Thai Royal College of Physicians, Chair, the HIV/AIDS biomedical research working committee, the AIDS research fund, Ministry of University Affairs, a member of the working committee on implementing antiretroviral therapy into the universal health care system, the AIDS Division, Ministry of Public Heath, Secretary of the Thai AIDS Society and chair of the Academic Sub-commitee on HIV Treatment and Care of the National AIDS Program, National Health Security Office (NHSO). Chris Duncombe is the editor of the 2009 update of the WHO guidelines for the use of antiretroviral Therapy in resource limited settings. Jintanat Ananworanich is a member of the writing committee for the Thai Ministry of Public Health pediatric antiretroviral treatment guidelines and the HIV subcommittee of the American Academy of Allergy, Asthma and Immunology. She serves as an independent expert for review of PMTCT and pediatric guidelines for the World Health South East Asia Region. She serves on the DSMB for the Southeast Asia Influenza Clinical Research Network and the steering committees for the Pediatric European Network for Treatment of AIDS and Treat Asia. She is an organizing committee member of the 2009 and 2010 International Workshop on HIV Pediatrics. She serves on the Scientific Assessment Panel of the HIV Research Trust Award. She is deputy editor for AIDS Research and Therapy, editor for Open Virology Journal and reviewer for various journals such as Lancet and AIDS. Anchalee Avihingsanon is a member of the expert panel working group of the Thai Ministry of Public Heath HIV/AIDS management guidelines, a member of the expert panel working group on antiretroviral therapy practice policy guidelines, a member of

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the Thai Royal College of Physicians, an external reviewer for P Qualify Ph.D Examination, a member of the working committee on implementing antiretroviral therapy into the universal health care system, the AIDS Division, Ministry of Public Heath. She is also a lecturer for local hospitals and international training courses in HIV, all opportunistic infections and complications. 54

Thanyawee Puthanakit is a member of the expert panel working group of the Thai Ministry of Public Heath HIV/AIDS on antiretroviral therapy practice policy guideline, a member of the WHO technical reference group Pediatric HIV/ART care, a member of the Treat Asia Steering Committee.

The Thai Red Cross AIDS Research Centre (TRC-ARC) In 2009, there have been many ongoing and newly established activities in the Thai Red Cross AIDS Research Centre (TRC-ARC), the mother organization of HIV-NAT. Thai Red Cross Anonymous Clinic Thai Red Cross Anonymous Clinic has gradually accomplished its goal to reduce stigma of the clinic. More clients, both HIV-negative and HIV-positive, come in now for a wide range of services such as STD clinic, cervical and anal Pap smear clinic, assisted conception clinic for discordant couples and health check-up clinic. MSM sexual health clinic With support from the American Foundation for AIDS Research (amfAR), MSM Sexual Health Clinic has been set up at the Thai Red Cross Anonymous Clinic since April 2008. The number of MSM clients attending the service has been increased rapidly this year which led the TRC-ARC to officially establish its “Men’s Health Clinic” this year. The opening of the Clinic in June 2009 was a huge success with many organizations working with MSM and mass media attending the press release event. There were 4,167 MSM clients who attended the Clinic during April 2008 – July 2009. Of these, 880 (21%) received anal Pap smear and 157 (18%) had abnormal cytology results from ASC-US and above. Around 70% of MSM clients who received anal Pap smear were HIV-positive MSM. Rate of the abnormal cytology results among HIV-positive MSM was around 2.5 times higher than HIV-negative MSM. Among 4,167 MSM clients who attended the Clinic, 1,603 (38.5%) had known positive HIV status, 1,242 (29.8%) had known recent negative HIV status and 1,322 (31.7%) had unknown status. Of those with unknown status, 1,283 (97%) accepted anti-HIV testing and 314 (24.5%) were found to be HIV positive. Every client received individual risk assessment and risk reduction counseling and a total of 16,000 condoms and 4,000 lubricants were distributed without charge. The outreach peer educator has been conducting outreach activities weekly at various entertainment venues in 6 main MSM entertainment areas in Bangkok during night time. The MSMPOL (Popular Opinion Leader) camps have been held to create a new generation of MSM-POLs with knowledge and skills in MSM sexual health issues. Sperm Wash in HIV serodiscordant couples For serodiscordant couples (HIV-infected males), sperm wash is an alternative technique to have their own children while protecting the female partners from HIV infection. The Thai Red Cross Anonymous Clinic has set up a sperm wash and intrauterine insemination (IUI) service since August 2006. During August 2006 and September 2009, 106 serodiscordant couples were registered for the service and 99 (93.4%) passed psychosocial screening. Among these, 87 came for semen analysis and 64 (73.5%) had adequate sperm count (> 20 millions/ml). Seminal HIV-1 RNA was detectable in 16.4 % (12/73) with HIV-1 RNA range of 45-213,000 copies/ml (Log 1.65-5.32). Semen HIV-1 RNA was not correlated with plasma HIV-1 RNA (R 2 = .305). Among 87 eligible men, 81 came for sperm wash and IUI. All washed sperm specimens had HIV-RNA < 50 copies/ml. There were 204 cycles of sperm wash with 182


IUI attempts done in these 81 couples. Fifteen out of 81 (22.64%) couples became pregnant and the IUI success rate was 9.3% per cycle. The median trial before successful insemination was 2 cycles (1-6). Four (33.3%) pregnant women had spontaneous abortion, 1 had abortion twice. Successful pregnancy was not correlated with CD4, viral load or antiretroviral treatment. All pregnant women were anti-HIV negative after the first trimester of their pregnancy. Latent and active tuberculosis screening studies Latent TB screening has now been incorporated as one of the routine services at the Thai Red Cross Anonymous Clinic. Adherence rate to INH Prophylaxis Therapy (IPT) is high and follow-up effort to assess the development of active TB in the following years is ongoing. PMTCT and MTCT-Plus TRC-ARC along with a panel of experts from the University Hospitals, the Department of Health, and the Thailand-US CDC Collaboration launched new TRC-ARC PMTCT Guidelines in 2008 with the modification of recommended antiretroviral regimens for pregnant women in each CD4 cell count strata. Boosted lopinavir or efavirenz-based regimen is now recommended for those with CD4 cell count >350 cells/mm3 while NVP-based regimen is still the recommended regimen for those with low CD4 cell count. Efforts have been made to propose the Guidelines to the national and international audiences. MTCT-Plus program, the life-long care and treatment program for women beyond delivery and their family members supported by funding through Columbia University and TRC-ARC public donation, has continued to provide cares to its participants. Thailand has been very successful for having high enrollment rate of male partners and very low rate of HIV infection in infants as compared to many other MTCT-Plus sites in Africa. More than 600 adult patients are now on antiretroviral therapy in this program with more than 95% adherence. Current model has now seriously incorporated routine screening for cardiovascular risk factors including metabolic complications from antiretroviral treatment, nutritional problems and cervical cancer. Thai-Australian Collaboration in HIV Nutrition (TACHIN) Under the collaboration with the Albion Street Centre in Sydney and the Institute of Nutrition, Mahidol University, the Thai-Australian Collaboration in HIV Nutrition (TACHIN) was established in April 2005 and funded by a grant from AusAID. TACHIN is currently staffed by 1 research dietitian and 2 nurse nutritionists with its mission to improve the quality of life of HIV-infected adults and children through nutritional manipulations. The aim of improving the nutritional health of PLHIV was achieved by setting up and subsequently strengthening a variety of nutrition interventions through HIV services already established at the Thai Red Cross. The project developed interventions in five key areas of intervention. These included HIV nutrition advocacy, clinical nutrition care, community-based nutrition activities, care provider education and operational researches. TACHIN nutrition services have been provided at the Thai Red Cross Anonymous Clinic to more than 700 clients per year using referral system. TACHIN 001 study has been conducted in our nutrition clinic to study the role of dietary counseling and nutrition education in the ongoing care of people living with HIV in Thailand. TACHIN nutrition camps were carried out under the Italian Red Cross-funded â&#x20AC;&#x153;Let Food Be Your Medicineâ&#x20AC;? project since July 2008. During August 2008- April 2009, seven nutrition camps were held by middle-sized hospitals under this project in the Northern, Southern, Eastern, and Central parts of Thailand. The main objective is to empower participants in identifying nutrition problems and responding effectively to the issues. All camps with Nutrition Game Stations are acceptable as an effective and

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fun nutrition training module for HIV-affected families in Thailand and may well be applicable to other Asian countries. Factors for the success included great involvement of local people in the planning, excellent teamwork, and tailored nutrition messages for each region. 56

TACHIN healthy snack competition was held during April-July 2009. This event aimed to promote nutrition awareness as part of long-term care for people living with HIV through the promotion of nutritive foods. The recipes for the healthy snacks in each region of Thailand have been collected to develop a recipe book to be distributed to the communities in the near future. The Thai Nutrition Taskforce for HIV (TNT-HIV) is a national committee, appointed in 2008, which composed of Thai experts in HIV and nutrition from various organizations including the Thai Ministry of Public Health, Institution of Nutrition, Mahidol University and TACHIN. In 2009, TNT-HIV 001 study has been implemented to assess nutritional status among na誰ve HIV-infected patients and HIV-infected patients receiving highly active antiretroviral therapy. This study has enrolled 580 clients at the Thai Red AIDS Research Centre, Bamrasnaradura Infectious Disease Institute, Sanpathong, Suratthani, Khonkaen and Queen Savang Vadhana Wattana Memorial Hospital. In addition, TACHIN is ideally placed to share knowledge and experience in HIV nutrition across the region. The Laos-Thai-Australian collaboration in HIV Nutrition (Laos-TACHIN) project has been conducted in Champassak province since July 2008. Laos-TACHIN has focused on nutrition care and also more broadly on comprehensive care treatment for HIV disease. For HIV treatment and care, the Thai Red Cross AIDS Research Centre, which is a co-partner of TACHIN project with strong experience in HIV care in the region, has been the leader organization in building capacity of HIV service system and health care worker in Champassak province. In May 2009, the first Basic HIV Nutrition Training was provided to physicians, nurses and peer educators there by Laos-TACHIN. This is helpful for them to apply knowledge and experience shared by Thais into their clinical practice setting. Life Skills Development for the Prevention of HIV/AIDS and STIs among Youth in Slum Communities Youths in slum community were reached by outreach workers of the Thai Red Cross AIDS Research Centre. Many of them are out-of-school youths. Several workshops were organized to enhance life-skill and knowledge on the prevention of HIV/AIDS, sexually transmitted infections and reproductive health issues since youths especially in slum communities are one of the most vulnerable populations. Research Project for Capacity Building of Service Provision at Anonymous Clinic to Reduce Vulnerability of HIV Infection To ensure the quality of voluntary counseling and testing for HIV/AIDS, this project was initiated to monitor and evaluation services provided by the personnel of the anonymous clinic. The project also encourages the personnel of anonymous clinic to provide feedback of what skills they need to acquire. This project gathers the information from both clients and counselors to ensure the involvement of all parties and constructive ways of quality development. Life skill for HIV/AIDS and Drug Abuse Prevention in Juvenile Detention Centers The project is an intervention for the prevention of HIV/AIDS among youths detained in the Juvenile Detention Centers in Thailand. Several workshops based on life skill curriculum and participatory approach were used to enhance skills of youths so that they are equipped with knowledge that will help protect them from HIV/AIDS infection when they are released and continue their lives in the broad society. The development of HIV/AIDS Implementation Standard for Tambon Administration Organization Based on the theory that all local public health system will be supervised by the local administration, this project was initiated to develop guidelines for personnel in the


Tambon Administration Organization so that clear policies and implementation can be applied and share the same standard throughout the country. Wednesday’s day friend club A group of HIV-infected patients at the HIV clinic, Chulalongkorn University Hospital, Bangkok was formed under the believe that people with similar life experiences offer good psychological, moral, social and spiritual support for each other. The club provides extensive contact and resource information on treatments. Wednesday’s day friend club was formed in 1990 initially in Bangkok, but has expanded its coverage to the 76 provinces of Thailand currently with approximately 4, 000 members. The club goal is primarily to prevent the spread of HIV. Activities of club include personal counseling, public information campaigns, workshops and a newsletter called “Red Ribbon Newsletter”.

South East Asia Research Collaboration with Hawaii (SEARCH) SEARCH is a partnership that began in 2005 with a goal of accomplishing mutual objectives in HIV/AIDS research and training in the South East Asia region between 3 partners: The Thai Red Cross AIDS Research Centre (TRCARC) and HIV-NAT in Bangkok, The Hawaii AIDS Clinical Research Program of the John A. Burns School of Medicine, University of Hawaii (UH) at Manoa in Honolulu, and The Armed Forces Research Institute of Medical Sciences (AFRIMS) in Bangkok. SEARCH has 3 codirectors: Professor Praphan Phanuphak (TRCARC), Professor Cecilia Shikuma (UH), and COL. Jerome Kim (AFRIMS). SEARCH is directed by Dr. Jintanat Ananworanich as the Chief and Dr. Nittaya Phanuphak as the Deputy Chief. Clinical Studies SEARCH 001/001.1 Predictors of neuro-cognitive decline and survival in HIV-infected subjects This 144-week study follows the neurocognitive outcome and HIV DNA of Thais with and without HIV-associated dementia. Data at 48-week showed improved neurocognition after HAART. HIV DNA from monocytes correlated to cognitive performance irrespective of HIV RNA and CD4 lymphocyte. Subjects are seen at Phramongkutklao Hospital and at SEARCH. The study will complete in 2010. SEARCH 002 Establishing normal values for neuropsychological testing in Thais This study has enrolled 350 of 500 HIV negative Thais to establish normal values for neuropsychological testing panels. The public can request use of this data via the SEARCH website (www.searchthailand.org). Subjects are enrolled at Phramongkutklao Hospital and at SEARCH. The study will complete in 2011. SEARCH 003 Comparing the toxicity profile of d4T-based regimen as lead-in for the first 6 months versus AZT-based and TDF-based first line regimens. The study has completed enrollment of 150 patients whom will be followed for 72 weeks. There are sub-studies to evaluate mitochondrial toxicity, neurotoxicity and pharmacokinetics of nucleosides. Subjects are seen at the TRCARC and Queen Savang Vadhana Memorial Hospital. The study will complete in 2011. The study is funded by the US NIH (R01 AI074554-01A1 and R01 NS063932-01) SEARCH 007 HIV-1 Specific Immune Responses in Thai Individuals with HIV Dementia This study is enrolling 60 patients over 4 years to assess the HIV-1 specific CD4+ T helper cell and CD8+ CTL responses, and monocyte/macrophage dysregulation/ activation in individuals with and without HIV-associated dementia prior to and after

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HAART. Subjects are enrolled at Phramongkutklao Hospital and at SEARCH. The study is funded by the US NIH (R01 NS053359-01A1) and will complete in 2012. SEARCH 008 Cohort study of HIV-1 Incidence among clients of the Thai Red Cross AIDS Research Centre, Bangkok, Thailand This study has enrolled over 900 HIV negative subjects to assess HIV incidence, risk behavior and willingness to participate in prevention trials. The study is funded by the US Military HIV Research Program and will complete in 2010. SEARCH 010 Establish and characterize an acute HIV infection cohort in a Thai high risk population This study has enrolled 7/30 acutely infected subjects with acute HIV infection (HIV antibody negative, nucleic acid positive) whom will be followed for 2 years. Investigations of the immune response and HIV subtypes in the peripheral blood, gut and central nervous system are done. Subjects are offered mega HAART for the first 6 months followed by standard HAART. The study is funded by the US Military HIV Research Program and by the US NIH (R21MH086341) SEARCH 011 Peripheral Reservoir of HIV DNA in Monocytes Pivotal to Cognition in HIV This study is enrolling 60 subjects at Phramongkutklao Hospital and at SEARCH. It will determine the long-term relationship between cognition and HIV DNA in circulating monocytes and define the longitudinal relationships between HIV DNA in monocytes and cerebrospinal fluid biomarkers and MRS findings. The study is funded by US NIH (R01 AI075408-01) and will complete in 2013. Immunologic Markers as Predictors of TB-associated IRIS in HIV/TB Co-infected Thais This recently completed study found an IRIS incidence of 17.5% (22/126) among Thais with advanced HIV infection/TB. There appears to be an increased in interferon gamma response to PPD at time of IRIS. This study is a collaboration between SEARCH, Chulalongkorn University, Bamrasnaradura Institute & Columbia University. Improving the Diagnosis and Management of Latent TB in Thai Children This study is enrolling 166 children with history of TB contact to assess the sensitivity and specificity of the interferon-gamma release assays and tuberculin skin test in screening for latent TB in HIV-positive and â&#x20AC;&#x201C;negative children. The study is a collaboration between SEARCH, HIV-NAT, Queen Sirikit National Institute of Child Health and Columbia University. The study is funded by the REACH Initiative Award. Identifying Biomarkers to Detect Anal Intraepithelial Neoplasia among Thai Men who have Sex with Men This study is enrolling 120 subjects to identify biomarkers (HPV subtype, p16, MCM proteins, E6 and E7 mRNA) that can be used as adjunct tool to anal cytology in the detection of high risk anal intraepithelial neoplasia. The study is funded by amfAR. RECENT PUBLICATIONS 1 Arroyo MA, et al. Increased Prevalence of Non-CRF01_AE HIV-1 Strains among High-Risk Clients Attending the Thai Red Cross Anonymous Clinic in Bangkok, Thailand. AIDS Res Hum Retro (In Press) 2 Van Tieu H, et al.


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Immunologic Markers as Predictors of Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome in HIV and TB Co-infected Persons in Thailand. AIDS Res Hum Retro 2009 (Nov 3) 3 Manosuthi W, et al. Clinical Case Definition and Manifestations of Paradoxical Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome. AIDS 2009; 23(18):2467-71 4 Li AH, et al. Anal squamous intraepithelial lesions among HIV-positive and HIV-negative men who have sex with men in Thailand. Sex Trans Inf 2009; June 11 5 Valcour VG. et al. HIV DNA and Cognition in a Thai Longitudinal HAART Initiation Cohort: The SEARCH 001 Cohort Study. Neurology 2009; 72(11):992-8 6 Ananworanich J, et al. Incidence and Characterization of Acute HIV-1 Infection in a High-Risk Thai Population. JAIDS 2008; 49(2):151-5 7 Ratto-Kim S, et al. Expression of monocyte markers in HIV-1 infected individuals with or without HIV associated dementia and normal controls in Bangkok Thailand. J Neuroimmunol 2008; 195(1-2):100-7 8 Valcour VG, et al. Neuropsychological abnormalities in patients with dementia in CRF 01_AE HIV-1 infection. Neurology 2007; 68(7):525-7 TRAINING SEARCH coordinates training upon request including basic and advanced HIV training, and second line antiretroviral therapy for adults and children. SEARCH has coordinated training for PEPFAR Vietnam, WHO India, UNICEF China and amfAR TREAT Asia. SEARCH believes in a team-approach to HIV care and provides joint learning to physicians, nurses, peer educators and laboratory technicians. Such team approach training is provided yearly and is funded by the Gilead Foundation. SEARCH has been working towards building infrastructure for Neuro AIDS research in South East Asia by providing training and quality assurance in neuropsychological testing to nurses and neurologic examination to physicians. SEARCH holds the SEARCH Research Forum every year to encourage collaboration in Neuro AIDS studies.


Community Outreach Programs HIV-NAT, the Thai Red Cross AIDS Research Centre 2009 60

The hiv-nat pediatric team with three pediatricians, three nurses and one nurse assistant, three full time social workers (funded by the three charities), and two hiv-infected teenage peer educators has been taking care of almost 300 hiv-infected children and their families. hiv-nat has three charities with a mutual goal to provide care that encompasses all aspects of a childâ&#x20AC;&#x2122;s well being. Born to Live Charity The Born to Live Charity is founded by HIV-NAT and Father Sean Smith from the Missionaries of The Sacred Heart Development Centre in Adelaide, Australia. This program started in 2004 and has helped over 100 children with HIV and their families by supplementing family living cost, paying for school fees, school uniforms and books, helping with transportation costs to clinic visits, and paying for tests and medications for the children and their parents. The charity covers the cost for social workers to visit childrenâ&#x20AC;&#x2122;s homes and provide funds to hold camps for children and their families to have fun and to learn how to cope and live with HIV. In addition, every year a Born to Live ambassador is selected by voting by HIV-infected teens to visit members of the Born to Live Charity in Adelaide. For more information, please visit www.borntolive.org ART AIDS Fund (AAF) This charity is supported by Mr. Han Nefkens of the ART AIDS fund in the Netherlands. ART AIDS Fund in Thailand was started in August 2005 with a goal to provide an opportunity for children with HIV in Thailand to live a healthier and happier life. As of August 2009, ART AIDS has helped 111 children by providing funding for salvage antiretroviral therapy, laboratory testing and educational cost. These children are from HIV-NAT, Siriraj Hospital, Queen Sirikit National Institute of Child Health, Baan Gerda, Camilian Orphanage, and Chiangrai province. AAF also provides scholarships for children infected and affected by HIV and supports special educational funds for disabled children with HIV. AAF has an emergency medical fund that allows HIV-NAT to provide treatments that are not covered by the Government health care program and covered cost of hospitalization of children who need to be cared for at Chulalongkorn University Hospital. Starting in 2008, AAF also helps HIV-infected adults for medical care that they would otherwise not be able to access. Moreover, AAF also granted funds for two clinical research: one on hepatitis B revaccination in HIV-infected children after immune recovery and the other on HIV prevention program in Men who have sex with Men. For more information, please visit www.artaidsfund.org Living & Loving charity The fund is raised in the United Kingdom. The Living and Loving trustees are Dr. Andrew Hill, Dr. Sabine Kinloch and Ms. Olivia Tulloch. This program was started in 2006 with a goal to provide an opportunity for children with HIV in Thailand to live a healthier life by subsidizing their living cost and supporting them with HIV medications and HIV care. Currently Living & Loving charity is helping over 150 HIV families from HIV-NAT and Khon Kaen University Hospital. Living & Loving charity also has an emergency medical fund to provide life saving treatment that is not covered under the government health care program. In Khon Kaen, the Charity has a silk project that helps families of children with HIV improve their silk making skills. The charity helps them sell their silk products to ensure that they receive fair and good income for their products. For more information, please visit www.livingandloving.org


In addition, we have developed an integrated website called www.DekTank.org to link the activities of the 3 charities. Dek means children and Tank refers to Tower II at the Thai Red Cross AIDS Research Centre where the children come to hang out and chat with our social workers. This website also includes stories told by our youth volunteers and caregivers of children with HIV, and web board and chat room for youth. 61

Summary art camps and workshops 1 Meeting of Volunteer Youth Group (10 January 2009, Tower II, Thai Red Cross AIDS Research Center, Bangkok) Objectives: To enable youth living with HIV, peer volunteer group to exchange their experience in their work to promote and advocate peer support to help those affected by HIV/AIDS among interested peer groups 2 Youth Forum (21-22 February 2009, Chonburi Province) Objectives: To allow 28 Youth living with HIV and Peer Volunteer Group to meet and exchange their experience with youth volunteers who work on HIV/AIDS and Thai Youth Volunteer Network and to enhance cooperation and networking 3 Art for happiness camp 2 (31 March-3 April 2009, Rayong Province) Objectives: To continue developing children’s ability and potential by stimulating their imagination.

4 Preteen art camp II (21-24 April 2009, Saraburi Province) Objectives: Preteen To encourage exploration in various fields of art including drawing, photography, short film, music and performance. In addition, art is implemented as a process to heal children’s psychological and emotional trauma. The children learned art with ease and enjoyment, while not being judged (no right or wrong). Through their art works children will find their potential and realize that they are no different from other children; Youth volunteer Group To learn various arts, the same as in the preteen group. The relationship between the two groups (preteen and youth) will serve as a basis for group support. In the long term, the youth volunteer will help their friends and younger children to understand HIV/AIDS and to overcome the problem and/or difficult situation; The caretaker group To communicate and exchange the experience of HIV/AIDS. 5 How to take care of disabled children Workshop (14-15 May 2009, Camillian Home for disabilities people, Ladkrabang, Bangkok) Objectives: The participants understand the children’s disabilities and know how to communicate and promote their development and to strengthen the network among the NGO who work with disabled children, hospice, family and HIV-NAT


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6 Understanding about HIV/AIDS camp (17-19 July 2009, Samudsongkram province) Objectives: To provide the correct information to children with HIV and assist them in developing a positive attitude. 7 Mother group support (6 August 2009, Tower I, the Thai Red Cross AIDS Research Center, Bangkok) Objectives: To provide the correct information to mothers and fathers about mother to child transmission and to set up a group support. 8 Small group activities: Life skill (22 August 2009, Tower I, the Thai Red Cross AIDS Research Center, Bangkok) Objectives: To relay the correct HIV information to teenage groups and provide them with essential life skills. 9 CAB CAB is comprised of representatives from the affected population, community leaders, people from the wider community, activists, relevant HIV networks and organizations, and academics in society who have played active roles in the field of HIV medicine and civic movements. CAB meeting is provided once a month at TRCARC


International Advisory Board 2009

Members Mr. Phan Wannamethee (Chairman) The Secretary General The Thai Red Cross Society Bangkok, Thailand Dr. Tej Bunnag Assistant Secretary General The Thai Red Cross Society Bangkok, Thailand Prof. Emeritus Praphan Phanuphak Director of The Thai Red Cross AIDS Research Center Thai Red Cross Society Bangkok, Thailand Prof. David A Cooper Director of National Centre in HIV Epidemiology and Clinical Research The University of New South Wale Sydney, Australia Prof. Joep M A Lange Chief Scientific Adviser AMC-IATEC Department of International Medicine University of Amsterdam, the Netherlands Prof. Ploenchan Chetchotsakd Faculty of Medicine, Khonkaen University Khonkaen, Thailand Prof. Sean Emery National Centre in HIV Epidemiology and Clinical Research The University of New South Wale Sydney, Australia Dr. Michael Malison Director HIV/AIS Research Program Thailand MOPH-US CDC Collaboration, Ministry of Public Health Nonthaburi, Thailand Dr. Annette Sohn amfAR Vice President of Global Initiatives and Director, TREAT Asia Bangkok, Thailand Lt COL Robert M Paris Chief, Department of Retrovirology USAMC-AFRIMS Bangkok, Thailand Assoc. Prof. Adisorn Patradul Dean Faculty of Medicine, Chulalongkorn University Bangkok, Thailand Prof. Peter Speelman Board of the Center of Poverty-related Communicable Diseases, Department of Internal Medicine Academic Medical Centre-AMC University of Amsterdam, the Netherlands

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ACKNOWLEDGMENTS

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We would like to express our sincere gratitude and appreciation to the following Institutional Review Boards (IRBs), without whom these studies would not be possible: 1 The Institutional Review Board of the Faculty of Medicine Chulalongkorn University 2 The Ethical Review Committee for Research in Human Subjects Ministry of Public Health (MOPH) 3 Internal Ethics Committee Chiangrai Prachanukroh Hopital 4 The Siriraj Institutional Review Board (SIRB) 5 Institutional Review Board of Bamrasnaraduru Infectious Diseases Institute 6 Committee on Human Rights Related to Researches Involving Human Subjects Faculty of Medicine, Ramathibodi Hospital 7 Research and Ethic Committee Chonburi Regional Hospital 8 Research and Ethic Committee Queen Savang Vashana Memorial Hospital 9 Research and Ethic Committee Prapokklao Hospital 10 The Ethics Committee for Human Research Khon Kaen University 11 Ethics Committee For Researches Involving Human Subjects The Bangkok Metropolitan Administration 12 The Ministry of Health Institutional Review Board of Cambodia


SPONSORS

International Support Pharmaceutical/Industries Abbott Avexa Limited Boehringer Ingelheim Pharmaceuticals, Inc Bristol-Myers Squibb Chiron Corporation GlaxoSmithKline Gilead Sciences Janssen-Cilag Ltd Matrix Merck & Co., Inc NUMICO ROCHE Pharmaceutical Tibotec Pharmaceuticals Academic Organizations AMC Center for Poverty-related Communicable Diseases University of Amsterdam National Centre in HIV Epidemiology and Clinical Research (NCHECR) University of New South Wales (Sydney, Australia) Research Institute of Tuberculosis Tokyo Japan University Medical Centre Nijmegen Research Organizations Pediatric European Network for Treatment of AIDS Swiss HIV Cohort Study Funding Agencies Foundation for AIDS Research United States (amfAR) Global Fund to Fight AIDS, Tuberculosis, and Malaria

Charities Art AIDS Fund is supported by Mr. Han Nefkens from The Netherlands Born to Live Charity Living & Loving Charity Bristol-Myers Squibb provides life-time ATV for some patients. Gilead-Sciences provides Truvada for some patients. ROCHE Pharmaceutical provides life-time SQV for all patients from HIV-NAT 001.4, STACCATO, HIV-NAT 019, T-20 and GEMINI. Global Fund to Fight AIDS, Tuberculosis, and Malaria supports ARV and some CD4 and viral load testing. Domestic Support Governmental Agencies Commission of Higher Education Ministry of Education Governmental Pharmaceutical Organization Ministry of Public Health National Health Security Office National Research Council of Thailand Social Security Office Thai Research Fund Academic Organizations Chulalongkorn University The Royal College of Physician of Thailand Research Organizations HIV-NAT Knowledge Network Institute of Thailand Thai Red Cross AIDS Research Centre Family Health International

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HIV-NAT 2009 Annual Report  

HIV-NAT 2009 Annual Report