1. Hepatitis C among people who inject drugs (PWID) in India: High burden but limited access to care Shruti H. Mehta, PhD MPH Professor, Johns Hopkins Bloomberg School of Public Health Department of Epidemiology Baltimore, MD July 21, 2014

2. Hepatitis C and injection drug use in India  Limited surveillance data  Estimated prevalence of HCV In the general population: 1- 2%  Predominantly HCV genotype 3 infection  Estimated 1.1 million PWID in India Aceijas 2007; Sievert 2011; Chakravarti 2005

3. Presentation outline & Data sources 1.Burden of HCV and liver disease among PWID in India 2.Access to care and treatment for HCV among PWID in India 3.Challenges / opportunities The India IDU Initiative – Cross-sectional sample of 14,481 PWID from 15 sites (~1000 per site) from Dec 2012 – Dec 2013 – Recruited using respondent-driven sampling (RDS) Diversity of HCV among PWID – 810 HIV-infected persons sampled across 15 sites from 2009 – Jan 2011 Chennai HIV, HCV and Eeral (liver disease) study[CHHEERS] – ~ 800 PWID sampled in Chennai – Detailed characterization of liver fibrosis Chennai (CHE)

4. Established epidemics Large cities Emerging epidemics (documented) Emerging epidemics (anecdotal) High burden of hepatitis C infection and HIV/HCV coinfection in India (n=14,481) Hepatitis C antibody prevalence HCV/HIV co-infection prevalence Solomon IAS 2014 (POSTER LBPE13); Solomon EASL 2014

5. Tamil Nadu Rajasthan Mizoram Manipur West Bengal Uttar Pradesh Punjab New Delhi Subtype 1a Subtype 1b Subtype 3a Subtype 3b Subtype 6n Predominance of genotype 3 HCV infection but variability by region Solomon CROI 2013

6. High burden of liver fibrosis / cirrhosis Chronic HCV HIV / HCV co-infection Mehta EASL 2014; Solomon et al AIDS 2009

7. Moderate fibrosis (LSM 8-12.3 kPa) Severe fibrosis / cirrhosis (>12.3 kPa) Odds ratio95 % CIOdds ratio95% CI Age (per 5 years) 1.050.92 – 1.191.241.06 – 1.46 Body mass index (per 2 kg/m 2 )1.131.01 – 1.261.151.02 – 1.32 Hepatitis C virus Negative HCV RNA<2.8 log 10 IU/ml HCV RNA 2.8 – 5 log 10 IU/ml HCV RNA 5 – 6 log 10 IU/ml HCV RNA > 6 log 10 IU/ml 1 0.63 0.43 2.66 2.21 0.28 – 1.43 0.05 – 3.55 1.26 – 5.64 1.34 – 3.65 1 2.03 3.14 6.69 6.49 0.88 – 4.67 0.69 – 14.3 2.92 – 15.4 3.58 – 11.7 Hepatitis B Surface Antigen+2.081.04 – 4.122.401.09 – 5.31 HIV Negative HIV + CD4 >500 cells/ul HIV+ CD4 200 – 500 cells/ul HIV+ CD4 <200 cells/ul 1 1.39 0.97 0.57 0.57 – 3.37 0.50 - 1.90 0.12 – 2.69 1 0.61 0.54 1.87 0.16 – 2.32 0.23 – 1.27 0.62 – 5.68 Fibrosis, cirrhosis associated with traditional risk factors…

8. Moderate fibrosis (LSM 8-12.3 kPa) Severe fibrosis / cirrhosis (>12.3 kPa) Odds ratio95 % CIOdds ratio95% CI Alcohol dependence None Harmful drinking Hazardous drinking/dependence 1 1.02 1.61 0.47 – 2.23 0.93 – 2.77 1 2.35 3.16 0.95 – 5.82 1.10 – 6.37 Insulin Resistance (HOMA-IR >2)1.681.06 – 2.642.331.38 – 3.95 Steatosis None Mild Moderate 1 1.55 2.96 1.01 – 2.40 1.47 – 5.96 1 1.53 2.65 0.92 – 2.54 1.10 – 6.37 …but also strong associations with metabolic cofactors

9. Rapid HCV disease progression? No/mild fibrosis at baseline: Fibroscan <8 kPa 31% experienced progression to moderate fibrosis 12% experienced progression to severe fibrosis/cirrhosis Moderate fibrosis at baseline: Fibroscan 8-12.3 kPa 47% experienced progression to severe fibrosis/cirrhosis

10. The hepatitis C care continuum (aka CLIFF) n=5,777 Minimum Maximum Solomon IAS 2014 (POSTER LBPE13); Solomon EASL 2014

11. Variability by stage of drug use epidemic… Solomon IAS 2014 (POSTER LBPE13); Solomon EASL 2014

12. …but no variability by stage of liver disease

13. Barriers to HCV+ diagnosis 14,450 persons 13,178 (91%) NEVER tested for HCV 1,272 (9%) EVER tested for HCV 6721 (51%) NEVER heard of HCV 6,457 (49%) Heard of HCV 73% cited low risk perception 14% did not know where to get tested 73% cited low risk perception 14% did not know where to get tested 53% wanted to know their status 25% were referred by a physician 44% tested in private/NGO testing centers / 41% in government centers Testing more common in sites with established epidemics Solomon IAS 2014 (POSTER LBPE13); Solomon EASL 2014

14. Facilitators of HCV+ diagnosis Unadjusted Odds Ratio (95% CI) Adjusted Odds Ratio (95% CI) Age (per 10 year increase)1.21 (0.94, 1.57)1.14 (1.00, 1.29) Marital Status Never married Currently married 1 1.30 (0.83, 2.04) - Education Primary Secondary High School graduate 1 2.04 (1.32 - 3.13) 4.54 (2.71 - 7.63) 1 1.92 (1.24, 2.97) 4.01 (2.35, 6.84) Ever visited OST center2.95 (1.76, 4.93)1.87 (1.02, 3.41) Ever tested for HIV8.08 (5.15, 12.68)3.58 (2.40, 5.33) Knowledge of HIV status Positive and unaware Positive and aware Negative 1 9.06 (3.99, 20.6) 1.48 (0.62, 3.53) 1 5.51 (2.57, 11.83) 1.18 (0.48, 2.92) Region of Residence Northeast Large cities Emerging epidemics (documented) Emerging epidemics (anecdotal) 1 0.18 (0.09, 0.35) 0.24 (0.08, 0.73) 0.06 (0.02, 0.21) 1 0.28 (0.11, 0.75) 0.27 (0.16, 0.46) 0.11 (0.04, 0.28) Note: also examined gender, years of drug use, lifetime frequency of injection, needle sharing, utilization of other services (SNEP, TB treatment, etc.) Solomon IAS 2014 (POSTER LBPE13); Solomon EASL 2014

15. Challenges  Co-factors complicate disease progression & treatment response – Metabolic co-factors (e.g., steatosis, insulin resistance) – High burden of alcohol use  Subtype diversity – Access to HCV genotype testing important for management  Low levels of knowledge: start with HCV literacy  Limited access to care & testing locations  Cost

16. Opportunity: Integrate HCV testing & treatment with HIV and harm reduction services Services to be delivered HCT Antiretroviral therapy (ART) Testing for sexually transmitted infections Opiate substitution therapy (OST) Needle & syringe exchange (NSEP) Condom Promotion Information Education and Counseling Testing of Spouses Counseling for depression/substance abuse TB treatment (via DOT) ClinicalTrials.gov Identifier: NCT01686750 Hepatitis B vaccination HCV testing & Treatment

17. Acknowledgements  Funding sources – NIDA (DA12568, DA032059, DA026727) – OAR (I to I program) – ICMR  Johns Hopkins – Sunil Solomon – Gregory Lucas – David Celentano – Allison McFall – Mark Sulkowski – Dave Thomas  NACO, India  YRGCARE – Suniti Solomon – AK Srikrishnan – M Suresh Kumar – AK Ganesh – S Anand – P Balakrishnan – CK Vasudevan – Accounts – Data Team – Lab Team  Site staff & participants