Prevention strategies for HIV/HCV co infection

www.ias2013.org Kuala Lumpur, Malaysia , 30 June - 3 July 2013

Prevention strategies for HIV/HCV co infection

Isabelle Andrieux-Meyer, MDMédecins Sans Frontières

IAS Kuala Lumpur, July 2nd 2013.



• Epidemiological burden of HCV/HIV co-infection

• Access to HCV screening• Right to care and Vulnerable groups• Management of co-morbidities• Treatment is prevention


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)


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


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


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




• HCV screening: for whom?• Right to care and Vulnerable groups• Management of co-morbidities• Treatment is prevention


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 .


Two different Scenarii

Generalized HCV epidemic: in the general population (Africa)

Concentrated epidemic: prisons, Injection Drug Users (IDU)


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)


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 (EY laboratories) 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)


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)


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).


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.


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.


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


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


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


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.


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

Agent Daily dose (mg)

Overall dose for 12 weeks (g)

Production estimate(usd/g)

Predicted cost (usd)

Ribavirin 1000-1200 84-100 0.25-0.75 21-63 for 1000mg, 25-76 for 1200mg

Daclatasvir 60 5 2-6 10-30

Sofosbuvir 400 34 2-4 68-136

Faldaprevir 120 10 10-21 100-210

Simeprevir 150 13 10-21 130-270


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!


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

Prevention strategies for HIV/HCV co infection

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