Update on Hepatitis C SSHA Conference 2015 Daniel Bradshaw Locum Consultant GUM/HIV Brighton and Sussex University Hospitals NHS Trust

Overview Epidemiology Natural history of HCV Acute HCV in HIV-positive MSM Diagnostic tests for HCV Treatments – old and new Treatment as prevention

Global anti-HCV prevalence 230K PLW HCV in UK; around 8K HCV/HIV coinfected

Easterbrook et al IAS 2015

Natural history of HCV 20 % spontaneous clearance HCV acquisition 80 % chronic infection 20% develop cirrhosis after 20 yr Add refs – see my intro to MD; indication for liver transplant in UK 1-4% per year risk of hepatocellular cancer Freeman et al Hepatol. 2001

Public Health England website 2015; vertical 2-8%. Increased in HIV Public Health England website 2015; vertical 2-8% ? Increased in HIV. Mention prevalence in PWID in UK, Scotland, Europe. Universal screening of blood donors in 1991 – risk is 1 in 2 million

Transmission of HCV infection Route of Exposure HCV HIV HCV transmission compared to HIV Parenteral (needlestick) 1.5-3% 0.3% > x10 Permucosal (sexual) 0.1-0.3% 1-5% < x10 Vertical 2-5% 20-30% < x6-10 So lest move on to look at those at risk for acute HCV . Certainly the predminant route of transmission for HCV is via parenteral exposure i.e. blood to blood contact traditioanlly through bllod transfusions, injecting drug use , unsafe mediacl injections. Epithelial target cell not right target unlike hiv

HCV transmission: HIV-negative, HCV-discordant heterosexual couples Study Type of study Study population N Duration follow-up Incidence /1000 person years (cases) Kao 2000 Prospective Taiwanese 112 46 m 0.23 (1) Vandelli 2004 Italian 776 120 m 0.37 (3) Tahan 2005 Turkish 216 36 m None Terrault 2013 Cross-sectional American 500 180 m 0.72 (3) Despite this sexual transmission has generally been traditionally associated with very low risk – such that guidelines do not recommend condoms in hetersexual relationships . Overall risk is <1% per year Here a number of cohort studies following discordant couples with very low rates of new infections – a yearly transmission risk of < 1% Nb 180m is the median time (15 years) of the reported monogamous relationship Terrault – low transmission risk 1 per 190,000 sex contacts; excluding HIV infected couples and where percutaneous risk identified in both partners. 500 couples No condom guideline  1 transmission per 190,000 episodes of sex

HCV seroprevalence in high–risk STI groups suggests sexual risk is present Risk group Anti-HCV Associated factors FSWs 6% Number of partners, other STIs, sex with trauma, non-use of condoms STI clinic 4% Risk for IDU > sexual factors. In non IDU : number of partners, high-risk sexual contacts, HIV+ MSM In non IDU : HIV+, number of partners, sexual practices In fact HCV seroprevalence data in highrisk sexual groups would suggest there is an incraesed risk This is a USA study – all available seroprevalence figures combined Retrospective data. Seroprevalence Oz 1-2% Terrault Hepatology 2002

Characteristics of the study population, by hepatitis C virus (HCV) serostatus in EUROSIDA cohort Characteristics of the study population, by hepatitis C virus (HCV) serostatus at recruitment into the EuroSIDA cohort. 6000 patients All HIV-positive 33% overall were HCV+ 7% acquiring HIV via MSM contact were HCV+ (Ab or RNA) 78% acquiring HIV via IDU were HCV+ Rockstroh et al 2005

Acute HCV in HIV-positive MSM

Acute HCV in the Swiss HIV Cohort Study Wandeler et al CID 2012

Countries reporting acute HCV in HIV+ MSM Apers 2015 Browne 2004 Gotz 2005 Vogel 2005 Gambotti 2005 EHSSS 2009 Wandeler 2012 Nishijima 2013 Sanchez 2013 Orsetti 2013 Luetkemeyer 2006 Sun 2012 Chan 2015 Evolving since London Public Health Agency of Canada, Hep C & STI, surveillance and epi section. Epidemiology of acute hepatitis C infection in Canada: results from the enhanced hepatitis strain surveillance system (EHSSS) 2009. Characteristics – 30s/40s, MSM, HIV+, well controlled, mostly deny IDU New – Taiwan, Japan Matthews 2007

Potential factors for increasing permucosal transmission in HIV+ MSM Behavioural 1. Serosorting1 2. Mucosal trauma2,3,4 3. Mucosally-administered recreational drugs2,3,4 Biological 1. HIV5,6 2. STIs2,3,4,7 Chronic hCV – increased HCV shedding in semen if HIV+ Lattimore et al 2011 Danta et al 2007 Schmidt et al 2011 MMWR Morb Mortal Wkly 2011 Briat et al 2005 Sherman et al 2005 Van de Laar et al 2007

Detection of HCV in semen Check alignments of words etc and colours Bradshaw et al JID 2015

Serosorting behaviour amongst MSM Prevalence, correlates and trends in seroadaptive behaviours among men who have sex with men from serial cross-sectional surveillance in San Francisco, 2004–2011 Jonathan M Snowden1, Lattimore 2011, london Lattimore et al STD 2011

Changing patterns of drug use in MSM 2005 2012 Crystal meth 0% 40% GBL/GHB 3.2% 27% Mephedrone 18% Ref via GUM/A&E/statutory drugs services 8% 63% Mention ASTRA study Daskalopoulou M et al.Sexual behaviour, recreational drug use and hepatitis C co-infection in HIV-diagnosed men who have sex with men in the United Kingdom: results from the ASTRA study. J Int AIDS Soc17(Suppl 3):19630, 2014. David Stuart 2013

Mechanism of sexual transmission of HCV in HIV-infected MSM High-risk practices Shared implements Sexual practices Drug practices Group Sex Sexual transmission of HCV Internet ‘Club drugs’ STI Permucosal NOT parenteral transmission

HCV reinfection in HIV-infected MSM 200 individuals of survival free from reinfection for patients previous treated for their HCV infection, shown in light gray, and individuals who spontaneously cleared their first HCV infection. As you can see, there is a trend to a higher reinfection rate among individuals treated but this did not reach significance. One startling point to take from this graph is that, as you can see, approximately 25% of individuals treated for HCV infection were reinfected within 2 years. 144 patients Martin AIDS 2013 Martin et al AIDS 2013

Incidence of HCV in HIV-positive MSM in Amsterdam HCV IR among 761 HIV+MSM (observed and fitted) HCV IR by age in 2008 Vanhommerig et al, JAIDS, 2014 2

Acute HCV in HIV-negative MSM 44 patients identified 35 of 44 patients had subsequent HIV testing within the department and remain negative Median time since last HIV test until now= 5.6 months (range 0.2- 40.4 months) 9 patients had no further HIV tests 20% were on PREP *************** McFaul et al J Viral Hep 2015

Diagnostic tests for HCV infection Anti-HCV antibody HCV antigen HCV RNA Antigen 30-45 days before Ab; Fibroscan assessment of liver fibrosis

When to test for HCV in HIV-positive MSM? 1) After very high risk (high risk sex with HCV+ partner) OR if liver enzymes abnormal HCV Ab and PCR Repeat PCR at 4 weeks. 2) After high risk (but normal liver enzymes) HCV Ab Repeat Ab at 12 weeks. 3) Repeat testing (Ab and PCR) at 3-6 monthly intervals if ongoing high risk 4) Annual HCV Ab testing if not high risk Ref the DS HCV testing survey – see boesecke rockstroh for REF BHIVA Guidelines on Viral Hepatitis 2013

HCV treatments

Reasons for treatment of HCV in HIV-infected individuals Transmission Stigma More rapid progression of liver disease Increase in HIV related comorbidities Increase in HAART toxicity

Multiple organ dysfunction in HCV/HIV coinfection

Cult Health Sex. 2008 Aug;10(6):601-10. doi: 10.1080/13691050802061673. An 'elephant in the room'? Stigma and hepatitis C transmission among HIV-positive 'serosorting' gay men. Owen G. Sex Health. 2013 Jul;10(3):268-74. doi: 10.1071/SH12179. Perceptions and deflections: associations between attitudes towards people with hepatitis C and testing for hepatitis C among Australian gay and bisexual men. Brener L1, Ellard J, Murphy D, Callander D. “An 'elephant in the room'?” Stigma and hepatitis C transmission among HIV-positive 'serosorting' gay men Owen G Cult Health Sex 2008

New anti-HCV therapies

HCV SVR rates between 1990 - 2014 Webster et al Lancet 2015 Figure 1 Changes in standard of care for HCV, and improvements in numbers of sustained virological responses Data from references 9–12. PI=protease inhibitor. Webster et al Lancet 2015 The Lancet 2015 385, 1124-1135DOI: (10.1016/S0140-6736(14)62401-6)

Cost in India, Egypt - chart

MODELLING PROJECTIONS: EDINBURGH Martin NK, et al. Hepatology 2013

Salazar-Vizcaya et al CROI 2015 CROI 2015 poster 675 rauch Behavioural and Treatment Interventions to Reduce HCV Transmissions in HIV+ MSM Author(s):  Luisa Salazar-Vizcaya1, Roger Kouyos2, Cindy Zahnd1, Manuel Battegay3, Katharine Darling4, Alexandra Calmy5, Pietro L. Vernazza6, Olivia Keiser1, Andri Rauch Salazar-Vizcaya et al CROI 2015

Two-mode social network diagrams of HIV+ MSM with acute HCV and venues used for sourcing sexual partners Melbourne Sydney Bradshaw et al AASLD 2013

Summary Epidemic of acute HCV in HIV+ MSM with mostly sexual acquisition High levels of reinfection in this cohort New HCV therapies equally effective in both HIV+ and HIV- individuals In the UK, new HCV therapies are currently only available to cirrhotic patients Reducing the epidemic will require increases in levels of testing, treatment and effective behavioural interventions

Acknowledgements Professor Mark Nelson

THANK YOU