Prevention strategies for HIV/HCV co infection

1. Prevention strategies for HIV/HCV co infection Isabelle Andrieux-Meyer, MD Médecins Sans Frontières IAS Kuala Lumpur, July 2nd 2013.

2. Prevention strategies for HIV/HCV co infection • Epidemiological burden of HCV/HIV co-infection • Access to HCV screening • Right to care and Vulnerable groups • Management of co-morbidities • Treatment is prevention

3. Epidemiological burden of HIV/HCV coinfection Worldwide between 150 and 170 million people live with hepatitis C infection. (WHO 2012) The majority of them are not aware of their infection. ( Lavanchy Liver Intl 2009) Between 4 and 5 million people living with HIV are currently co-infected with HCV .( Easterbrook Sem Liv Dis 2012) While HIV can be controlled by antiretroviral therapy, co-infected people die from HCV related complications, like liver cirrhosis or liver cancer.( Nelson Lancet 2011). Chronic HCV infection is independently associated with a 50% increase in mortality among patients with a diagnosis of AIDS. ( Branch CID 2012)

4. New HCV /HIV epidemiological data. Center for Disease Analysis 2013 (1)

5. New HCV /HIV epidemiological data. Center for Disease Analysis 2013 (2)

6. Access to reliable epidemiological data: a game –changer! • We expect • WHO to organize and coordinate sentinel epidemiological HBV and HCV surveillance systems for resource limited settings. • Country health authorities need access to reliable data in order to measure the magnitude of the domestic and regional disease burden and prioritize the response accordingly. • This means access to reliable rapid diagnostic tests • And a political will to confront the real burden of the HCV pandemic

7. Prevention strategies for HIV/HCV co infection Epidemiological burden of HCV/HIV co-infection HCV screening: for whom? Right to care and Vulnerable groups Management of co-morbidities Treatment is prevention

8. Primary prevention /HCV transmission • Blood to blood contact. • Transmission in developed countries: • 90% chronic HCV infection were infected through transfusion of unscreened blood ( Alter JAMA 1990) • Or sharing contaminated needles or other drug injection equipment ( Villano SA, Drug and Alcohol Dependance 2009).HCV seroprevalence among drug users ( IDU) : 60% (Nelson PK, Lancet 2011) • Less commonly HCV is transmitted by sexual contact with an infected person, including MSM, or birth to an infected mother.( Wandeler G CID 2013) • In developing countries: • the primary sources of HCV infection are unsterilized injection equipment and infusion of inadequately screened blood and blood product .

9. Two different Scenarii Generalized HCV epidemic: in the general population (Africa) Concentrated epidemic: prisons, Injection Drug Users (IDU)

10. Some MSF figures • HCV prevalence in blood donors 2012: Centre African Republic: 7.1%, DRC: 8.5%, Nigeria: 7.2% ( MSF Operational Center Amsterdam) • Manipur India: prospective cohort analysis among 468 people infected with HIV, 50.6% are co infected with HCV.(MSF Operational Center Amsterdam) • HCV screening in Ukraine: 74% of prisoners in MDRTB project are HCV positive. ( MSF Operational center Brussels)

12. Access to HCV testing: game -changer Globally, 59% of the world’s population has no access to hepatitis C diagnosis. These findings correlate with the wealth of the country: Dx using serology is available in 53% of lower middle income countries, and 11% of low income countries( WHA report 2010). MSF RDT (rapid diagnostic test) procurement: HCV Scan (EYlaboratories) sensibility: 100%, specificity: 93.7% ( WHO 2001) HCV Spot (MP Medicals) Average price 1-4 EUR per test. New line OraQuick(Orasure, USA): Best and most up to date performance but 10-12x more expensive than other RDTs.( sensibility: 99.2%, specificity: 99.8% ( Lee 2010) ( MSF HCV landscape analysis 2013) => Limited evidence on the accuracy of HCV RDTs in HIV/HCV coinfection. ( Shivkumar Ann Intern Med 2012)( Smith J Itl Dis 2011)

13. HCV confirmation test: Detection of HCV RNA • Anti-HCV antibodies indicate exposure to the virus, but cannot determine if infection is present or if the infection has cleared spontaneously. • All persons with positive anti-HCV antibody test must undergo additional testing for the presence of the HCV itself to determine whether current infection is present and whether there is an indication for treatment • HCV PCR is the most common method to detect viral RNA. It is also used to quantify the virus for treatment monitoring purpose. Usually: Abbott, Roche, Siemens quantitative VL. • HCV PCR is hardly accessible and costs >=100 USD per test. • We need affordable : • POC HCV Viral load : pipeline Wave 80, Alere, Cepheid, IQuum, Daktari. • Flexible PCR platforms ( Multitest: HBV-HIV-HCV) like Sacace generic open platform test, or Qiagen. ( MSF HCV landscape analysis)

15. Genotyping & Fibrosis evaluation (1) The required length of peg-IFN-ribavirin treatment, the current standard of care, and the expected outcome from treatment, is dependent on the HCV genotype. Tests, using a range of different technologies: Abbott , Roche, Siemens tests Sacace: generic open platform test (real time PCR) Pipeline point-of-care test: Wave80 New oral drugs will allow for simplification , if we have access to pan-genotypic treatment then genotyping may not be needed Liver fibrosis can be assessed at field level using Transient elastography: Fibroscan, or serum biomarkers like APRI( Lin ZH. Hepatol 2011).

16. Prevention strategies for HIV/HCV co infection Epidemiological burden of HCV/HIV co-infection Access to HCV screening Right to care and Vulnerable groups Management of co-morbidities Treatment is prevention

17. Universal access to care, right to care and vulnerable groups (1) (Asian Network of People who Use Drugs 2011 report) • Decriminalization of IDU and stop discrimination / access to care. (Global Commission on drug policy 2013) • Access to Universal harm reduction programs : including adequate medical equipment, dead end syringes, cotton, water, needle exchange programs, safe injection places, oral substitution therapy programs, and peer education. • Education about infection control in medical settings, prisons.

18. Universal access to care, right to care and vulnerable groups (2) • Safe blood transfusions and medical dental practices, respect of universal hygiene precautions, HBV immunization. • Targeted screening adapted to epidemiological profile: HIV cohorts for HBV and HCV, annual risk assessment for vulnerable groups, including MSM.

19. Prevention strategies for HIV/HCV co infection Epidemiological burden of HCV/HIV co-infection Access to HCV screening Right to care and Vulnerable groups Management of co-morbidities Treatment is prevention

20. Management of co-morbidities • HBV immunization • Diabetes, insulino resistance, iron overload, alcohol, cannabis, tobacco, depression • Nutrition, physical activity • Early HIV treatment (<500CD4/mm3) • Treat TB or MDRTB first • Hepatic disease due to other viruses or alcohol • Avoid recontamination

22. Prevention strategies for HIV/HCV co infection Epidemiological burden of HCV/HIV co-infection Access to HCV screening Right to care and Vulnerable groups Management of co-morbidities Treatment is prevention

23. Treatment is prevention (1) • More data are needed for people living with HIV-HCV co-infection, and advanced liver disease. • Simplified diagnosis procedures and 2nd generation DAA treatment regimen will substantially increase impact and feasibility of treatment , and treatment as prevention ( Gane E, NEJM 2013, Poordad F, NEJM 2013) • Desirable drug characteristics for resource limited settings: • Pan genotype • Enhanced efficacy (likely >90% all genotypes) • Once/twice-daily oral-only dosing • Reduced toxicity • High barrier to resistance • Shortened treatment duration (~12 weeks) • Compatibility with liver advanced disease • Performance for treatment experienced people

24. Treatment is prevention (2) Several pharmaceutical companies develop molecules, some are in a position to develop their own FDC. We need phase III trial results to confirm the positive preliminary results, the following drugs are particularly interesting for RLS Gilead: SOFOSBUVIR based ( SOF-GS 5885-RBV) Sofosbuvir: FDA registration submitted April 10th 2013 for GT1 ( IFN sparing) and for GT2 and 3 all oral. Sofosbuvir-Ledipasvir : Plan to submit 2014 BMS: Daclatasvir –asunaprevir based combination Abbott: ABT 450/r + ABT-267 + ABT-333 + RBV Janssens: Simeprevir

25. Treatment is prevention (3) • Simplified treatment may lead to: • Higher uptake/adherence/completion • Integration, decentralization and scaling –up of HIV-HCV services, including vulnerable groups like injection drug users. • If the package of diagnosis and treatment can be largely available at affordable cost : < 500 usd.

26. Cost per person, for 12 weeks course of HCV DAA ( A. Hill IAS 2013. Abstract TULBPE16)

27. Conclusion: 170 million people living with HCV are left behind, 2 to 4 millions are co infected with HIV. • There is a revolution in HCV diagnostics and treatments. • Access to HCV screening and care is a matter of prioritization and political will. • Civil societies, patients groups, care givers, are key players. • Decriminalization and Universal access to care for the most vulnerable groups are urgently needed. • Increasing the demand and decreasing the price of key diagnosis and treatments for HCV will be possible by creating : • Operations • Price competition • New market dynamics • New treatment paradigms. It’s time for action!

28. Acknowledgments • MSF Hepatitis access team: T.Roberts, J.Cohn, M.Balasegaram, B.Milani, A.Rehman, K.Athersuch, N.Ernoult, L.Menghaney,P.Cawthorne, J.Arkinstall, A.Lee, J.Keenan, J.Rius. • S.Hargreaves, H.Razavi, A.Hill, N.Martin, U, Asian Network of People who use Drugs. • All participants to Treatment Action Group- Open Society Foundation -MSF September 2012 Meeting: A.Kamaralzuman, A.Volny-Anne, A.Fontanet, A.Momen, C.Perez, C. Forette, D.Wolfe, D.Osheret, D.Sylvestre, D.Donchuk, E.Tellis, E.Dos Santos Pinheiro, E.Torrele,F.Josephson, G.Esmat,G.Raguin, G.Khwairakpam, H.Bygrave, J.Arkinstall, JM Pawlotsky, K.Kaplan, K.Elouardighi, L.Ayada, L.Martelli, L.Castera, L.Gangte, L.Maistat, L.Mendao, M. Gastellu-Etchegorry, M.Luigi, M.Thursz, M.Serafini, N.Cantau, N.Durier, N.Luhmann, P.Sabelashvili, P.Cawthorne, P.Londeix, P.Du Cros, P.Easterbrook, P.Clayden, R.Stuikyte, R.Njouom, R.Wood, S.Kirollos, S.Eholié, S.Delaunay, S.Wiktor, S.Balkan, T.Ahmin, T.Yepthomi, T.Swan, W.Doss, Y.Yazdapanah, J.Rius, S.Lynch, S.Shettle, A.Lee, J.Keenan, L.McCullagh. • IAS : Alexandra Calmy, Marina Klein, Sharon Walmsley, Beatriz Grinsztejn • MSF landscape analysis report available at : http://www.msfaccess.org/content/diagnosis-and-treatment-hepatitis-c-technical-landscape