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Co-infections: Hepatitis C 1 What is Hepatitis? ‘hepat’ = liver ‘itis’ = inflammation Viral hepatitis…. A B C D E Faeco-oral, never chronic Blood, sexually transmitted, can be chronic Blood, sexually transmitted, often chronic Only with B, usually chronic Faeco-oral, rarely chronic VACCINE PREVENTABLE What is hepatitis C (HCV) ? • Known as ‘non A non-B’ hepatitis before 1989 • ‘Non-A non-B’ transfusion-related hepatitis • RNA virus that infects liver cells causing inflammation and, if untreated, liver scarring fibrosis • Since 1991 all UK blood transfusions have been screened Hepatitis A & B • Hepatitis A: is caught from infected water or food and although it can be serious, it only lasts for a short time. • It is advisable to get vaccinated before travelling to areas such as Asia, the Middle-East, Africa or Eastern Europe (check with GP/travel clinic) • Hepatitis B: is not caught from infected water or food but from infected blood or other body fluids. It often becomes an ongoing disease that could lead to liver cancer. How is HCV transmitted? • Most infectious fluid is blood Predominantly through injecting drug use Blood products, unclean surgical/injecting equipment Non-injecting drug equipment such as straws, diluents Piercing, tattooing (cleans needles AND ink!) • Or through sex Blood > sexual fluids; LOW levels in semen – MSM with rough sex practices particular risk Risk for heterosexual partners of HCV+, 0.07% a year1 • Mother to child but NOT via saliva or breast milk [1 Terrault NA et al. Hepatology 2013. [2] Bradshaw et al. Current Opinion 2013. [3] Wandeler G et al. CID 2012. Who is at higher risk of acquiring HCV? • People undergoing medical procedures in settings where infection control is poor • People who inject drugs (PWID) > people who ‘snort’ drugs • People with tattoos & piercings • Sexual partners of people living with HCV • HIV positive people (particularly men who have sex with men) • Infants of HCV+ mothers How widespread is HCV globally? (2014) Globally: How do HCV & HIV overlap? HIV 40 million HCV 10 million 175 million What is the impact of HIV on HCV? • More rapid liver fibrosis (scarring of the liver leading to Cirrhosis) • Worse at lower CD4 • Effective HIV treatment may negate this • HCV more infectious (PLWHA typically have higher HCV viral load in blood and semen) • Lower response rates to interferon-based treatment Liver-related death is a frequent cause of non-AIDS death in HIV positive people Deaths (%) D:A:D Study: Causes of death in n=49,734 HIV-infected patients followed 1999–2011 AIDS Liver-related disease Weber R, et al. AIDS 2012. Washington USA. Oral presentation THAB0304. Cardio -vascular or other heart disease Non-AIDS malignancies Other HCV Treatment- Old and New • Interferon/ Ribavirin was standard treatment for years • Lots of new drugs available now (DAA = direct acting antivirals) • But VERY EXPENSIVE so access is currently limited • Approaching 100% success rates for many groups, including those who are more difficult to treat e.g HIV+ Fatty liver/cirrhosis Older age Diabetes HCV/HIV SVR24 with Pegylated Interferon and Ribavirin- Poor Response Rates 100 Genotype 1 SVR 14–38% Genotype 3 SVR 44–73% SVR (%) 75 Monoinfection APRICOT ACTG RIBAVIC Laguno et al. PRESCO 50 25 0 G1 Genotype G2/3 Adapted from: Fried et al, NEJM 2002;347:975-982, Torriani et al, NEJM 2004;351:438-50, Chung R, et al, NEJM 2004;351:451-9 Carrat F, et al, JAMA 2004;292:2839-42, Laguno et al, AIDS 2004;18:F27-F36, Nunez et al, JAIDS 2007;45:439-44 5’UTR Core E1 E2 p7 How do I know which kind of DAA? NS2 NS3 ....previr (PI) ....asvir NS4B (NS5A) NS5A Protease Ribavirin NS3 Protease Inhibitors Telaprevir Boceprevir Simeprevir Asunaprevir Paritaprevir Grazoprevir 3’UTR NS5B Polymerase NS5A Replication Complex Inhibitors Daclatasvir Ledipasvir Ombitasvir Elbasvir GS-5816 *Representative list modified from CCO. *unlicensed NS5B NUC Inhibitors Sofosbuvir VX-135 IDX21437 ACH-3422 NS5B Non-NUC Inhibitors Dasabuvir Beclabuvir ....buvir (Pol) Drug-Drug Interactions between HCV drugs & ART Charts revised April 2015. NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor. www.hep-druginteractions.org (Accessed August 2015). Who needs treatment and treatment prioritization • IDEALLY recommended for all persons with chronic HCV infection (WHO, IAS-USA, EASL guidelines) • BUT increasingly treatments are prescribed (due to high cost and country guidelines) by prioritization How do EASL Guidelines Prioritise Need? Treatment ‘should be prioritized’ Treatment ‘justified’ •F3/F4 •F2 •Decomp. Cirrhosis •HIV or HBV coinfection •Liver transplant •Clinically significant extra-hepatic manifestation •Debilitating fatigue •(As of 2015) Individuals at risk of transmission (Grade B1) •‘Informed deferral can be considered’ F0/F1 EASL Guidelines, Journal of Hepatology, 2015 Acute HCV among HIV+ MSM Canada24: ~30 cases Prevalence chronic 19%: 11.200 HCV/HIV25 USA1,2: 55 cases Prevalence chronic HCV/HIV12–14 15 – 30%: 180.000 – 360.000 Europe: 1068 cases Prevalence chronic HCV/HIV14,15 25%: 185.500 - UK3,4 552 - Germany5,18, 28 157 - France6,7 126 Netherlands8,17 97 - Belgium20 69 - Swiss9 23 10 - Italy 21 - Denmark21 13 27 - Spain ~8 Lebanon22: 1 case Prevalence chronic HCV/HIV26 49%: 1.500 Australia11: 47 cases Prevalence chronic HCV/HIV16,19 < 1%: 1.000 1. Luetkemeyer JAIDS 2006; 2. Cox Gastroenterology 2008; 3. Giraudon Sex Transm Infect 2008; 4. Ruf Eurosurveill 2008; 5. Vogel CID 2009; 6. Gambotti Euro Surveill 2005; 7. Morin Eur J Gastro Hepat 2010; 8. Urbanus AIDS 2009; 9. Rauch CID 2005; 10. Gallotta 4th Works. HIV & Hep. Coinf. 2008; 11. Matthews CID 2009; 12. Sherman CID 2002; 13. Backus JAIDS 2005; 14. UNAIDS Report 2008; 15. Soriano JID 2008; 16. Matthews CID 2011; 17. Arends Neth J Med 2011; 18. Neukam HIV Med 2011; 19. Pfafferott PLoS One 2011; 20. Bottieau Euro Surveill 2010; 21. Barfod Scand JID 2011; 22. Dionne-Odom Lancet Infect Dis 2009; 23. Taylor Gastroenterology 2009; 24. Hull personal conversation 2011; 25. Remis 1st Canadian HCV Conference 2001; 26. UNGASS Country progress Report 2010; 27. Soriano personal conversation 2011; 28. Boesecke 18thCROI Boston 2011 abstract #113; 29. Sun Liver International 2011; 30. Lee J F, Med Assoc 2008. How/Why is HCV transmission continuing among MSM? • ‘Bare-backing’ • Rough sex causing bleeding • Other traumatic practices like piercing during sex, or saline scrotal inflation • Accidental or intended needle sharing • Sharing sex toys • Lack of testing for HCV • Sex with those with acute HCV/ seroconverters (ie with high viral loads) HCV: Where we are today with Unmet Treatment Need? • High burden of disease (80-130M with detectable virus) • Substantial uncertainty; need better surveillance • Increasing cause of death (700k deaths/year) • Highly effective Direct Acting Antiviral HCV therapy, but expensive and treatment rates extremely low • Need for informed prioritization strategies – mathematical modeling can help • 95% of HCV+ people were not receiving treatment in 2012 were not receiving HCV therapy Grebely & Dore, Journal of Antivir Ther , 2014 Conclusions • Liver disease is an important cause of morbidity and mortality in HIV positive people • Key issues = ART, HCV and lifestyle • HCV – – – – The era of DAA based therapy has arrived IFN-sparing and IFN-free therapy a reality Responses in HIV+ similar to HIVBeware DDIs • People with HIV are still a ‘Special Population’ despite similar response – as HCV aggressive, multi-system disease, urgent need of therapies • Need for improved cascade of care and access to therapies