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TREAT Asia cohort studies:Asia-Pacific region of the

IeDEA collaboration

Matthew Law

Kirby Institute, UNSW Australia

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TREAT Asia cohort studies TREAT Asia and IeDEA

TREAT Asia HIV Observational Database (TAHOD) TREAT Asia Studies Evaluating Resistance (TASER)

TREAT Asia Paediatric HIV Observational Database (TApHOD)

TAHOD Low Intensity Transfer (TAHOD LITE)

Conclusions

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TREAT Asia cohort studies TREAT Asia and IeDEA

TREAT Asia HIV Observational Database (TAHOD) TREAT Asia Studies Evaluating Resistance (TASER)

TREAT Asia Paediatric HIV Observational Database (TApHOD)

TAHOD Low Intensity Transfer (TAHOD LITE)

Conclusions

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TREAT Asia

Therapeutics Research, Education and AIDS Training in Asia

Supported by the Foundation for AIDS Research

Network of clinicians at sites around the Asia-Pacific region

TREAT Asia office in Bangkok Biostatistical centre at Kirby Institute, UNSW, Sydney, Australia

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TREAT Asia network

Pediatric sites (16)

Adult sites (21)

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2nd TREAT Asia Network Annual Meeting12-14 September 2002

Bangkok

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Region 5: Asia and Australia• Australia• Cambodia• China• Hong Kong• India• Indonesia• Japan• Malaysia• Philippines• Singapore• South Korea• Taiwan• Thailand• Vietnam

Region 10: East Africa • Kenya• Tanzania• Uganda

Region 11: Southern Africa • Botswana• Lesotho• Malawi• Mozambique• South Africa• Zambia• Zimbabwe

Region 9: Central Africa • Burundi• Cameroon• Rwanda

Region 2: Caribbean, Central and South America• Argentina• Brazil• Chile• Haiti• Honduras• Mexico• Peru

Region 1: North America • Canada• United States

Region 8: West Africa• Benin

• Burkina Faso• Côte d’Ivoire• Gambia• Ghana

• Guinea-Bissau• Mali• Nigeria• Senegal• Togo

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TREAT Asia cohort studies TREAT Asia and IeDEA

TREAT Asia HIV Observational Database (TAHOD) TREAT Asia Studies Evaluating Resistance (TASER)

TREAT Asia Paediatric HIV Observational Database (TApHOD)

TAHOD Low Intensity Transfer (TAHOD LITE)

Conclusions

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TAHOD/TASER

TAHOD recruits a subset of patients at sites Designed to assess treatment outcomes and risk factors From 2003, all data entirely observational 6468 patients recruited, 4496 in active follow-up

TASER recruited patients starting first or second ART Designed to assess resistance patterns Mandated viral load assessment annually – resistance testing in those failing 2025 patients recruited 1253 in active follow-up

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TAHOD/TASER

Combined TAHOD/TASER dataset 8493 patients recruited, 5749 in active follow-up quite detailed data, good follow-up good resource for treatment outcomes and risk factors

Not a surveillance mechanism subsample of patients seen at sites relatively small patient numbers

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CD4% and absolute CD4 counts in Asia

Absolute CD4 counts lower in Asian populations for a given CD4%

Uncertain significance

Achhra AC, et al. JAIDS & CR 2010;1:1-4.

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Risk of AIDS or death by CD4 count strata

CD4 count thresholds appear similar

<50 50-100 100-200 200-350 350-500 >5000

5

10

15

20

25

30

35

40

45

TAHOD (Asian)

AHOD (white)

Latest CD4+ counts, lagged by 3 months

Inci

denc

e ra

te p

er 1

00 p

erso

n ye

ars

Achhra AC, et al. JIAPAC 2011;10(3):160-70.

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Survival by PCP prophylaxis and CD4 count

Lim PL et al. JIAS 2012;15:1

67% of patients with CD4<200 receiving PCP prophylaxis

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Factors associated with virologic failure

      Multivariate  No of patients No of failures OR 95% CI p *Global pTotal 1173 120        

TDR     0.033

No TDR 1122 112 1  

TDR with susceptible ART 21 1 0.62 (0.08 to 4.68) 0.647  

TDR with suboptimal ART 30 7 3.12 (1.31 to 7.43) 0.010  

Pre-treatment CD4 (counts/uL)

    0.012

<=50 368 46 1  

51-100 183 19 0.88 (0.49 to 1.57) 0.662  

101-200 288 32 1.02 (0.62 to 1.68) 0.930  

201+ 305 18 0.41 (0.22 to 0.74) 0.003  

Missing 29 5        

~Adherence     <0.001

>=95% ~ 71 1  

<95% ~ 18 9.37 (5.00 to 17.6) <.001  

Missing ~ 31        

Phanuphak P, et al. JAIDS 2014;66:74-9.

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Resistance patterns

More resistance in recently infected than chronic: 6.1% vs 4.0% (p=0.065)

Kiertiburanakul S, et al. PLoS One 2013;8(6):e62057.

Chronic infectionRecent infection

Percentage

NNRTINRTI

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Factors associated with suboptimal adherence

More frequent adherence assessment associated with improved adherence

Jiamsakul A, et al. JIAS 2014;17(1):18911.

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Trends in CD4 count at ART initiation

Kiertiburanakul S, et al. JIAS 2014;17:18804.

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Time trends in ART at initiation

Boettiger D, et al. PloS One 2014 in press.

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TREAT Asia cohort studies TREAT Asia and IeDEA

TREAT Asia HIV Observational Database (TAHOD) TREAT Asia Studies Evaluating Resistance (TASER)

TREAT Asia Paediatric HIV Observational Database (TApHOD)

TAHOD Low Intensity Transfer (TAHOD LITE)

Conclusions

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TApHOD TApHOD recruits all children seen at sites

More representative than TAHOD Commenced 2008 5227 children recruited, 3504 in active follow-up

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Time to CD4≥25% after cART initiation

Handsudewechakul, R et al. JAIDS 2010;55(4):503-9.

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Weight and height for age scores from cART

Handsudewechakul, R et al. JAIDS 2010;55(4):503-9.

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Severe anaemia in first 6 months of HAART

Bunupuradah, T et al. Int J Infect Dis 2013;17:e806-e810.

Ever received AZT > 3-fold risk of severe anaemia (Hb<7.5 g/dL)

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Weight for age predicts survival

Kariminia A et al. JAIDS 2014 in press.

<-3SD >-3 to <2 SD >-2SD0

2

4

6

8

10

12

Weight for age Z-score

Rela

tive

risk

After adjustment for time updated CD4%

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Rates of all OIs in TApHOD

Mono/duo HAART

Prasitsuebsai W et al. PIDJ 2014;33:747-52.

Pre ART First 6 months

After 6 months

First 6 months

After 6 months

0102030405060708090

100

Rate

per

100

pyr

s

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TREAT Asia cohort studies TREAT Asia and IeDEA

TREAT Asia HIV Observational Database (TAHOD) TREAT Asia Studies Evaluating Resistance (TASER)

TREAT Asia Paediatric HIV Observational Database (TApHOD)

TAHOD Low Intensity Transfer (TAHOD LITE)

Conclusions

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TAHOD LITE Aim is to create a larger, but simpler, database

Include all patients seen at sites

Data to be included Demographics ART, CD4, HIV viral load Lost to follow-up, transferred clinics, survival

Eight sites currently will participate Anticipate ~50,000 patients who have started ART Data management and analysis at the Kirby Institute

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TAHOD LITE Creates something close to a surveillance mechanism

More representative sampling frame Much bigger patient numbers

Can answer more reliably questions like Trends in ART at initiation Trends in CD4 at initiation Rates of lost to follow-up

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TREAT Asia cohort studies TREAT Asia and IeDEA

TREAT Asia HIV Observational Database (TAHOD) TREAT Asia Studies Evaluating Resistance (TASER)

TREAT Asia Paediatric HIV Observational Database (TApHOD)

TAHOD Low Intensity Transfer (TAHOD LITE)

Conclusions

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Conclusions

Are databases like TAHOD still relevant and useful?

What are treatment outcomes as HIV-positive children age through adolescence and into adulthood?

What are long-term ART outcomes in Asia? are rates of CVD, cancer, liver and kidney disease similar to those seen in developed countries?

Will earlier and wider treatment across the region effect outcomes negatively?

poor adherence? Viral failure and resistance?

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Conclusions

TREAT Asia studies are region wide resource We have a dataset that might answer your questions

TAHOD/TASER Long–term treatment outcomes in adults

TApHOD Treatment use and outcomes in children

TAHOD LITE Time trends and treatment guidelines

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Plug

A Decade of Combination Antiretroviral Treatment in Asia: the TREAT Asia HIV Observational Database (TAHOD) Cohort

Nicolas Durier on behalf of TAHOD

WEPE070 – Wednesday 23 July 12.30-14.30

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TASER ACKNOWLEDGEMENTS

The TREAT Asia Studies to Evaluate Resistance is an initiative of TREAT Asia, a program of amfAR, The Foundation for AIDS Research, with major support provided by the Dutch Ministry of Foreign Affairs through a partnership with Stichting Aids Fonds, and with additional support from amfAR and the National Institute of Allergy and Infectious Diseases (NIAID) of the U.S. National Institutes of Health (NIH) and the National Cancer Institute (NCI) as part of the International Epidemiologic Databases to Evaluate AIDS (IeDEA) (grant no. U01AI069907). Queen Elizabeth Hospital and the Integrated Treatment Centre are supported by the Hong Kong Council for AIDS Trust Fund. The Kirby Institute is funded by the Australian Government Department of Health and Ageing, and is affiliated with the Faculty of Medicine, The University of New South Wales. The use of vircoTYPE™ HIV-1 is supported by Janssen Diagnostics BVBA.

• Members of the TASER study include:• PCK Li† and MP Lee, Queen Elizabeth Hospital and KH Wong, Integrated Treatment Centre, Hong Kong, China; • N Kumarasamy and S Saghayam, YRG Centre for AIDS Research and Education, Chennai, India;• S Pujari and K Joshi, Institute of Infectious Diseases, Pune, India; • TP Merati‡ and F Yuliana, Faculty of Medicine, Udayana University & Sanglah Hospital, Bali, Indonesia; • A Kamarulzaman and LY Ong, University Malaya Medical Center, Kuala Lumpur, Malaysia;• C KC Lee and B HL Sim, Hospital Sungai Buloh, Sungai Buloh, Malaysia; • M Mustafa and N Nordin, Hospital Raja Perempuan Zainab II, Kota Bharu, Malaysia;• R Ditangco and RO Bantique, Research Institute for Tropical Medicine, Manila, Philippines; • YMA Chen, YJ Chen and YT Lin, Taipei Veterans General Hospital and AIDS Prevention and Research Centre, National Yang-Ming

University, Taipei, Taiwan;• P Kantipong and P Kambua, Chiang Rai Regional Hospital, Chiang Rai, Thailand; • P Phanuphak and S Sirivichayakul, HIV-NAT/Thai Red Cross AIDS Research Centre, Bangkok, Thailand;• W Ratanasuwan and R Sriondee, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand;• T Sirisanthana and J Praparattanapan, Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand; • S Sungkanuparph, S Kiertiburanakul, and L Chumla, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand;• R Kantor, Brown University, Rhode Island, U.S.A.;• AH Sohn, N Durier and T Singtoroj, TREAT Asia, amfAR -- The Foundation for AIDS Research, Bangkok, Thailand; • DA Cooper, MG Law, and A Jiamsakul, The Kirby Institute, University of New South Wales, Sydney, Australia.•

† Steering Committee Chair, ‡ Co-Chair

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TAHOD ACKNOWLEDGEMENTS

• CV Mean, V Saphonn* and K Vohith, National Center for HIV/AIDS, Dermatology & STDs, Phnom Penh, Cambodia; FJ Zhang*, HX Zhao and N Han, Beijing Ditan Hospital, Capital Medical University, Beijing, China; PCK Li* and MP Lee, Queen Elizabeth Hospital, Hong Kong, China; N Kumarasamy*, S Saghayam and C Ezhilarasi, YRG Centre for AIDS Research and Education, Chennai, India; S Pujari*, K Joshi and A Makane, Institute of Infectious Diseases, Pune, India; TP Merati*, DN Wirawan and F Yuliana, Faculty of Medicine Udayana University & Sanglah Hospital, Bali, Indonesia;

• E Yunihastuti*, D Imran and A Widhani, Working Group on AIDS Faculty of Medicine, University of Indonesia/ Ciptomangunkusumo Hospital, Jakarta, Indonesia;

• S Oka*, J Tanuma and T Nishijima, National Center for Global Health and Medicine, Tokyo, Japan; JY Choi*, Na S, and JM Kim, Division of Infectious Diseases, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea;

• CKC Lee*, BLH Sim and R David, Hospital Sungai Buloh, Kuala Lumpur, Malaysia; A Kamarulzaman* † and A Kajindran, University of Malaya Medical Centre, Kuala Lumpur, Malaysia; R Ditangco*, E Uy and R Bantique, Research Institute for Tropical Medicine, Manila, Philippines; YMA Chen*, WW Wong and LH Kuo, Taipei Veterans General Hospital and AIDS Prevention and Research Centre, National Yang-Ming University, Taipei, Taiwan; OT Ng*, A Chua , LS Lee, and A Loh, Tan Tock Seng Hospital, Singapore; P Phanuphak*, K Ruxrungtham and M Khongphattanayothin, HIV-NAT/Thai Red Cross AIDS Research Centre, Bangkok, Thailand; S Kiertiburanakul* ‡, S Sungkanuparph and N Sanmeema, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; R Chaiwarith*, T Sirisanthana and W Kotarathititum, Research Institute for Health Sciences, Chiang Mai, Thailand; P Kantipong and P Kambua, Chiang Rai Prachanukroh Hospital, Chiang Rai, Thailand;

• VK Nguyen*, VH Bui and TT Cao, National Hospital for Tropical Diseases, Hanoi, Vietnam;• TT Pham*, DD Cuong and HL Ha, Bach Mai Hospital, Hanoi, Vietnam;• AH Sohn*, N Durier* and B Petersen, TREAT Asia, amfAR - The Foundation for AIDS Research, Bangkok, Thailand;• DA Cooper, MG Law*, A Jiamsakul* and D Boettiger, The Kirby Institute, The University of New South Wales, Sydney, Australia.

* TAHOD Steering Committee member; † Steering Committee Chair; ‡ co-Chair.

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TApHOD ACKNOWLEDGEMENTS

CV Mean, V Saphonn*, S Sarun, National Centre for HIV/AIDS, Dermatology and STDs, Phnom Penh, Cambodia;

V Ung*†, M Pok, Y Kdan, B Chan, National Pediatric Hospital, Phnom Penh, Cambodia;

J Tucker, New Hope for Cambodian Children, Phnom Penh, Cambodia;

FJ Zhang, Beijing Ditan Hospital, Capital Medical University, Beijing, China;

N Kumarasamy*, S Saghayam, E Chandrasekaran, YRGCARE Medical Centre, CART CRS, Chennai, India;

DK Wati*, LPP Atmikasari, IY Malino, Sanglah Hospital, Udayana University, Bali, Indonesia;

N Kurniati*, and D Muktiarti, Cipto Mangunkusumo General Hospital, Jakarta, Indonesia;

SM Fong*, M Thien, M Lim, F Daut, Hospital Likas, Kota Kinabalu, Malaysia;

NK Nik Yusoff*, P Mohamad , Hospital Raja Perempuan Zainab II, Kelantan, Malaysia;

KA Razali*, TJ Mohamed, NF Abdul Rahman, NADR Mohammed, Pediatric Institute, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia;

R Nallusamy*, KC Chan, Penang Hospital, Penang, Malaysia;

V Sirisanthana*, P Oberdorfer, L Aurpibul, T Sudjaritruk, Research Institute for Health Sciences and Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand;

R Hansudewechakul*, S Denjanta, W Srisuk, A Kongphonoi, Chiangrai Prachanukroh Hospital, Chiang Rai, Thailand;

P Lumbiganon*, P Kosalaraksa, P Tharnprisan, T Udomphanit, Division of Infectious Diseases, Department of Pediatrics, Khon Kaen University, Khon Kaen, Thailand;

G Jourdain, PHPT-IRD UMI 174 (Institut de recherche pour le développement and Chiang Mai University), Chiang Mai, Thailand;

T Bunupuradah*, T Puthanakit, W Prasitsuebsai, W Chanthaweethip, HIV-NAT/Thai Red Cross AIDS Research Centre, Bangkok, Thailand;

K Chokephaibulkit*, K Lapphra, W Phongsamart, S Sricharoenchai, Siriraj Hospital, Mahidol University, Bangkok, Thailand;

KH Truong*‡, QT Du, CH Nguyen, Children’s Hospital 1, Ho Chi Minh City, Vietnam;

VC Do*, TM Ha, VT An, Children’s Hospital 2, Ho Chi Minh City, Vietnam;

LV Nguyen*, DKT Khu, AN Pham, LT Nguyen, National Hospital of Pediatrics, Hanoi, Vietnam;

ON Le, Worldwide Orphans Foundation, Ho Chi Minh City, Vietnam;

AH Sohn*, N Durier, C Sethaputra, TREAT Asia, amfAR -- The Foundation for AIDS Research, Bangkok, Thailand;

DA Cooper, MG Law*, A Kariminia, The Kirby Institute, UNSW Australia, Sydney, Australia;

*Steering Committee member; † Current Steering Committee Chair; ‡ co-Chair