1. Hepatitis B and C virus Coinfection in the TREAT Asia HIV Observational Database Zhou J 1, Zhang FJ 2, Lim PL 3, Dore GJ 1, Chen YMA 4 on behalf of The TREAT Asia HIV Observational Database 1. National Centre in HIV Epidemiology and Clinical Research The University of New South Wales, Sydney, Australia 2. Ditan Hospital, Beijing, China 3. Tan Tock Seng Hospital, Singapore 4. AIDS Prevention and Research Centre and Institute of Public Health National Yang-Ming University, Taipei, Taiwan

2. BackgroundBackground ●Funded by amfAR ●A cooperative network of clinicians throughout the Asia-Pacific that aims to expand capacity for the broader introduction of HIV/AIDS treatments in the region ● ●First collaborative study by the TREAT Asia network ● ●A multi-centre, observational cohort of patients with HIV

3. Existing TAHOD sites New TAHOD sites Potential TAHOD sites 15 TAHOD sites at June 2006

4. IntroductionIntroduction WHO and UNAIDS estimate, worldwide 40 million living with HIV (2005) 370 million with chronic HBV infection 130 million with chronic HCV infection HAART leads to marked reduction of mortality and morbidity in patients with HIV HIV patients coinfected HBV and/or HCV Impact of coinfection on HIV disease progression and survival remains uncertain Much poorer liver disease outcome

5. ObjectiveObjective Prevalence of HBV and HCV coinfection in TAHOD Response to antiretroviral treatment CD4 count at 180 days after treatment initiation Time to undetectable HIV viral load (<400 copies/mL) Time to elevated liver enzyme (ALT) Overall survival after entry to TAHOD

6. MethodsMethods Definition of coinfection HBV coinfection: HBsAg positive HCV coinfection: anti-HCV antibody positive Patients who ever tested positive for HBV or HCV were regarded as coinfected for the duration of the study Statistical analyses Mean CD4 change from starting treatment – multiple linear regression models Time to undetectable HIV RNA, time to elevated ALT from starting treatment and survival from TAHOD entry – Cox proportional hazards models

7. Testing for hepatitis coinfection ● ● Testing for coinfection varies across TAHOD sites ● ● 90% ● ● Patients more likely to have an HBsAg test ● ● Higher baseline CD4 count ● ● Lower baseline HIV viral load ● ● Patients more likely to have an HCV test ● ● Reporting injecting drug use ● ● Higher baseline CD4 count ● ● Patients tested for EITHER HBsAg OR HCV antibody were included in the following analysis

8. Hepatitis coinfection in TAHOD ● ● 2979 patients in TAHOD as at September 2005 ● ● HBsAg positive – 171 / 1641 (10.4%) - Older age and reporting homosexual contact ● ● HCV antibody positive – 153 / 1469 (10.4%) - Reporting injecting drug use and blood products ● ● Initial antiretroviral treatment combination Stavudine + lamivudine + nevirapine Zidovudine + lamivudine + efavirenz - Regardless of hepatitis status

9. Mean CD4 change at 180 days after treatment initiation

10. Time to undetectable HIV viral load

11. Survival after entry to TAHOD

12. Time to elevated abnormal liver function test

13. ConclusionConclusion Prevalence of hepatitis coinfection in TAHOD ~10% Responses of antiretroviral treatment Mean CD4 recovery - Similar in HBV coinfected patients - Poorer in HCV coinfected patients (albeit not statistically significant) Time to undetectable HIV viral load - Similar in HCV and/or HBV coinfected patients No independent effect of coinfection on survival IDU and hepatitis testing Hepatitis coinfection associated with more hepatotoxicity

14. DiscussionDiscussion Limitations Hepatitis and liver enzyme tests limited in TAHOD patients Limited power due to short follow up Interpretation Coinfected patients do benefit from antiretroviral treatment Some evidence of increased hepatotoxicity Need to monitor liver function and other adverse events

15. The TREAT Asia HIV Observational Database The National Centre in HIV Epidemiology and Clinical Research 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. TREAT Asia and TAHOD are funded by a grant from the American Foundation for AIDS Research. CV Mean*, V Saphonn*, National Center for HIV/AIDS, Dermatology & STDs, Phnom Penh, Cambodia; F Zhang*, H Zhao and N Han, Beijing Ditan Hospital, Beijing, China; P Li* and MP Lee, Queen Elizabeth Hospital, Hong Kong, China; N Kumarasamy* and JA Cecelia, YRG Centre for AIDS Research and Education, Chennai, India; S Pujari*† and K Joshi, HIV Project, Ruby Hall Clinic, Pune, India; TP Merati* and F Yuliana, Faculty of Medicine Udayana University & Sanglah Hospital, Bali, Indonesia; S Oka* and M Honda, International Medical Centre of Japan, Tokyo, Japan; C KC Lee* and J Pang, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia; A Kamarulzaman* and C Sim, University of Malaya, Kuala Lumpur, Malaysia; R Ditangco* and R Capistrano, Research Institute for Tropical Medicine, Manila, Philippine; YMA Chen*, WW Wong and YR Chang, Taipei Veterans General Hospital and AIDS Prevention and Research Centre, National Yang-Ming University, Taipei, Taiwan; PL Lim*, CC Lee and LC Koh, Tan Tock Seng Hospital, Singapore; P Phanuphak*, and M Khongphattanayothing, HIV-NAT/The Thai Red Cross AIDS Research Centre, Bangkok, Thailand; A Vibhagool*, S Kiertiburanakul, and B Piyavong, Ramathibodi Hospital, Bangkok, Thailand; T Sirianthana* and W Kotarat, Research Institute for Health Sciences, Chiangmai, Thailand; J Chuah*, Gold Coast Sexual Health Clinic, Miami, Queensland, Australia; K Frost* and S Wong, American Foundation for AIDS Research, New York, USA; DA Cooper*, MG Law*, K Petoumenos and J Zhou*, National Centre in HIV Epidemiology and Clinical Research, The University of New South Wales, Sydney, Australia. * Steering Committee member. † Current Steering Committee chair.

16. Exposure category – Mar. 2006

17. Ethnicity – Mar. 2006

18. Patient follow up (Mar. 05 – Mar. 06) All TAHOD sites (Mar. 2005 - Mar. 2006)No.% A. New patients 81125.7 B. Died 12 month before 632.0 C. Died in the last 12 months 250.8 D. No follow up since entry to TAHOD 1294.1 E. Seen in the last 12 months 183558.2 F. Seen 12 months before 2909.2 Total3153100.0 Follow up rate = 82% ● ● Patient with follow up is defined as seen in the last 12 months (between 30 September 2005 to 30 September 2006) ● ● Patients died were considered as complete follow up ● ● Follow up rate = (B+C+E) / (B+C+D+E+F) * 100%

19. Follow up by site (Mar. 05 – Mar. 06)

20. Patient demographics – Mar. 2006 Male71% AgeMean (SD): 39.0 (9.98) (years, at recruitment) Median (IQR): 38 (32~44) CD4 countMean (SD): 319.3 (225.6) (cells/µL, at recruitment) Median (IQR): 290 (156~431) HIV viral loadMean (SD): 2.76 (1.36) (log 10 copies/mL, at recruitment) Median (IQR): 1.90 (1.69~3.90) Prior AIDS defining illness37 % Antiretroviral treatmentHAART: 77% (at recruitment) Mono/double: 2% Not treated: 21%

21. Publications from TAHOD The TREAT Asia HIV Observational Database: Baseline and Retrospective Data. J Acquir Immune Defic Syndr 2005;38(2):174-179. Predicting short-term disease progression among HIV-infected patients in Asia and the Pacific region: preliminary results from the TREAT Asia HIV Observational Database. HIV Med 2005;2005(6):1-8. Experience with the use of a first-line regimen of stavudine, lamivudine and nevirapine among TAHOD patients, HIV Medicine, in press. Highly active antiretroviral treatment containing efavirenz or nevirapine and related toxicity in the TREAT Asia HIV Observational Database, JAIDS, in press. AIDS defining illness diagnosed within 90 days after starting HAART among TAHOD patients, submitted to Int’l J STD & AIDS, under review.