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

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

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)

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

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

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

Moderate fibrosis (LSM kPa) Severe fibrosis / cirrhosis (>12.3 kPa) Odds ratio95 % CIOdds ratio95% CI Age (per 5 years) – – 1.46 Body mass index (per 2 kg/m 2 ) – – 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 – – – – – – – – 11.7 Hepatitis B Surface Antigen – – 5.31 HIV Negative HIV + CD4 >500 cells/ul HIV+ CD4 200 – 500 cells/ul HIV+ CD4 <200 cells/ul – – – – – 5.68 Fibrosis, cirrhosis associated with traditional risk factors…

Moderate fibrosis (LSM kPa) Severe fibrosis / cirrhosis (>12.3 kPa) Odds ratio95 % CIOdds ratio95% CI Alcohol dependence None Harmful drinking Hazardous drinking/dependence – – – – 6.37 Insulin Resistance (HOMA-IR >2) – – 3.95 Steatosis None Mild Moderate – – – – 6.37 …but also strong associations with metabolic cofactors

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 kPa 47% experienced progression to severe fibrosis/cirrhosis

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

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

…but no variability by stage of liver disease

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

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 (0.83, 2.04) - Education Primary Secondary High School graduate ( ) 4.54 ( ) (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 (3.99, 20.6) 1.48 (0.62, 3.53) (2.57, 11.83) 1.18 (0.48, 2.92) Region of Residence Northeast Large cities Emerging epidemics (documented) Emerging epidemics (anecdotal) (0.09, 0.35) 0.24 (0.08, 0.73) 0.06 (0.02, 0.21) (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

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

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: NCT Hepatitis B vaccination HCV testing & Treatment

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