Transcript Powerpoint

Scaling up screening , diagnostic
and treatments for HCV using the
HIV programs
Isabelle Andrieux-Meyer, MD
Médecins Sans Frontières
Access Campaign
International Aids Conference
Melbourne, July 22nd 2014
[email protected]
www.aids2014.org
Declaration of interest
• No conflict of interest
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Scaling up screening and diagnostics for HCV
using the HIV programs
- Access to reliable epidemiological data
- Access to HCV screening & diagnostic
- Who is the most at risk?
- Access to HCV treatments in 2014 in
LMIC?
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Global Prevalence of Hepatitis C
New HCV /HIV epidemiological data.
Center for Disease Analysis 2013
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Access to HCV screening: a game
changer
• Globally, 59% of the world’s population has no access to
hepatitis C diagnosis. Dx using serology is available in 53% of
lower middle income countries, and 11% of low income
countries ( WHA report 2010).
• HCV Scan (EY laboratories) sensibility: 100%, specificity:
93.7% ( WHO 2001) or HCV Spot (MP Medicals) : average
price 1-4 eur per test
• MSF recommends OraQuick (Orasure, USA): Best and most
up to date performance but 10-12x more expensive than other
RDTs.( 14 euros/test) (sensibility: 99.2%, specificity: 99.8% ( Lee
2010) Can be done on whole blood (e.g finger prick) or oral fluid.
( MSF HCV landscape analysis 2014)
• Limited evidence on the accuracy of HCV RDTs in HIV/HCV
coinfection. ( Shivkumar Ann Intern Med 2012)( Smith J Itl Dis 2011)
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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 .
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MSF UNITAID HIV-HCV grant
HCV public health problem, prevalence HCV –HIV co-infection
• 52.3% HCV-HIV co-infected patients in NE
India
• 67.2% in IDU in Iran
• 10.3% in Nairobi, Kenya
• 15.7% in Mozambique
• 29% in North Myanmar
• 53.3% among IDU in Ukraine
(Devi KS,I nis,2005)
( Seyed Alinaghi S, Acta Med Iran 2011)
(Muriuki BM, BMC Research notes 2013)
( Rodrigues, 2008)
( MSF OCA 2014, unpublished data)
( MSF OCB, unpublished data)
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Who is the most at risk?preliminary
investigation
• India: transgender people, people using drugs (IDU)
• Myanmar: Migrants, IDU
• Ukraine: prisoners, complex HIV patients , MDRTB,
TB patients, men who have sex with men ( MSM)
• Iran: Commercial sex workers (CSW) and partners,
IDU
• Mozambique &Kenya: IDU, CSW?, blood recipient,
invasive medical dental surgical procedure, tattoos,
health care workers, prisoners, mobile populations (
migrant workers, miners)
• Need to investigate patterns of transmission at country
level , collect epidemiological datas
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HCV confirmation test: Detection of
HCV RNA
• 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 2014)
Prohibitive Costs: Georgia: serology+ PCR RNA HCV+
genotype=USD135
Nigeria, India: package=500 USD
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3. Genotyping & Fibrosis evaluation
• The required length of peg-IFN-ribavirin treatment, or
oral treatments, 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) ( WHO HCV Guidelines 2014).
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Treatment should be simple, highly effective, pan-genotypic, potent, at
affordable cost, easy to take ( MSF HCV landscape analysis 2014)
Drug /combination
Overall Results
Sofosbuvir (SOF)
ribavirin ( RBV)
GT2, phase III 12weeks SVR12: 93%
SOF RBV
GT3 , phase III 24 weeks SVR12: 85%
SOF RBV
GT1 phase III 24 weeks SVR12: 76%
Peg-IFN +SOF+RBV
GT1 phase III 12 weeks SVR12: 90%
SOF + LDV(ledipasvir)
GT1 phase III 12 weeks SVR12 97.7%
SOF+LDV
GT1 phase III 8 weeks SVR12: 94%
SOF+ LDV+GS 9669
GT1 phase II 6 weeks SVR12 95% ( N=20)
SOF+LDV+GS 9451
GT1 phase II 6 weeks SVR12 100% ( N= 20)
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Drug/combination
Overall
resultsEASL 2014
3. Update
Sofosbuvir+ GS 5816
12 weeks
SOF 400mg+GS5816 100mg
N= 77
GT1: SVR12 28/28 :100%
GT2: 10/10 : 100%
GT3: 25/27 : 93%
GT4: 7/7
GT5: -Gt6: 5/5
(Everson EASL 2014)
Sofosbuvir+ledipasvir
HIV+HCV, N=50
SOF 400mg+GS5816 25mg
N=77
GT1 : SVR12: 26/27 : 96%
GT2: 10/11 : 91%
GT3: 25/27: 93%
GT4: 6/7
GT5: 1/1
Gt6: 4/4
GT1 no ART: SVR12: 10/10
GT1 on ART: SVR4: 21/21
( Osinusi A.EASL 2014)
Sofosbuvir ledipasvir
400/90 mg
Electron 2 ( EASL 2014 oral6)
GT3 12 weeks SOF+LDP+RBV : SVR12: 19/19 ( 100%)
GT3 12 weeks SOF+LDP: SVR12: 16/26 ( 64%)
Sofosbuvir ledipasvir
Electron 2 ( EASL 2014 oral6)
GT1 prior failure peg IFN +RBV: SOF+LDP+RBV: SVR12: 19/19
GT1 decompensated cirrhosis or Child B: SOF+LDP no RBV:
SVR12: 13/20 well tolerated
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The best components should be studied in combination and selected for market impact
(MSF HCV landscape analysis 2014)
Drug /combination
Overall results
SOF+simeprevir
SOF+simeprevir + RBV
GT 1phase II 12 weeks SVR12 100% (n=14)
SVR12 100% (n=12
SOF+Daclatasvir (DCV) GT1 phase II 12 or 24 weeks SVR12 100% ( n=14)
SOF+DCV+RBV
SVR12 95% ( n=15)
SOF +DCV
GT1 Naïve SVR12 98%
GT1 Experienced SVR12 98%
SOF+DCV
GT2 SVR12 92% (n=26)
SOF+DCV
GT3 SVR12 89% (n=18)
DCV+ asunepravir+
BMS 791325
GT1 phase II -12 or 24 weeks SVR12 94%
DCV 30mg+
simeprevir (SMV)+/RBV
GT1 SVR12= 75-85% in treatment naïve
SVR 12 = 65-95% in prior null responders
ABT 450/ +-ABT 267+ABT333+-RBV
phase III, GT1, tt naïve, 12 weeks:
3 DAA+ RBV : SVR12: 99.5%,3 DAA: SVR12: 99%
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Sovaldi : 84 000 USD for 12 weeks USA, 56 000 euros for 12 weeks in France
France, 1700 dollars in Egypt.
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Gilead Access program : 60 countries belong to the lowest tiered pricing category, price
negotiations for sofosbuvir ‘s price start at 300 - 350 USD per bottle of 28 tablets 900 –
1000 USD for 12 weeks . ( Gilead PR, February 2014)
(there is also a compassionate use program)
If you need to buy peginterferon: Merck: negotiate the Egyptian price: 40 USD per vial,
including ribavirin!
If you need to buy ribavirin to combine to sofosbuvir: Zydus: minimal quantity 750,000
caps, price per caps: 0.30 USD.
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Best price!
• ribavirine zydus price: 0.30 usd per caps.
1 caps= 200mg, daily dose average 1000 mg if <75 kg = 5 caps
so 12 weeks tt will cost : 126 usd
24 weeks tt will cost 252 usd
best price :
• 12 weeks sofosbuvir + ribavirine = 1000 +
126 = 1126 usd
12 weeks sofosbuvir+ ribavirine + pegifn =
1000+126+500 = 1626 usd
24 weeks sofosbuvir + ribavirine = 2000 +
252 = 2252 usd
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COST PER PERSON, FOR 12 WEEK COURSE OF HCV DAA
Agent
Daily Dose
(mg)
Overall dose for
12wks (g)
Production cost
estimate ($/g)
Predicted cost
($)
Ribavirin
1200
101
0.34*
50**
Daclatasvir
60
5
4.0
20
Sofosbuvir
400
34
3.0
102
MK-8742
50
4
11.0
44
MK-5172
100
8
8.9
71
Ledipasvir
90
8
11.6
93
* current mid-point cost of API from 3 Chinese suppliers
**shows cost for 1200mg daily dose; $41 for 1000mg daily dose of ribavirin
Courtesy Andrew Hill. Poster LBPE12. IAC 2014.
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BUNDLE OF CARE COSTS- A. HILL-
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Interventions to overcome access
barriers to HCV treatment
• Access to reliable epidemiological data , investigation of the
patterns of transmission.
• Access to reliable and affordable diagnostics ( WHO prequalified, rapid diagnostic tests, multi-analytic PCR platforms ,
Point of Care HCV viral load).
• Access to care without discrimination, including people who
use drugs.
• Demonstration projects: performance & feasibility at large
scale, simplification, task shifting, training, including
screening-prevention-harm reduction-treatment in different
epidemiological contexts.
• Free generic competition
• Goal: diagnostic –treatment package< 500 USD per cure.
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Remerciements
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IAC team:J. Rockstroh, S. Moroz, A. Madden, T. Swan, S. Baghani, L. Golob,
G. Dore.
WHO team: S.Wiktor, P. Easternbrook, N.Obara, N. Ford, G.Hirnschall, A.
Harmanci, C.Penn, A. Ball.
HCV Guidelines Development Group:
B.Smith; Y.Falck-Ytter, R.Birgin;
S.Bowden; V.Chulanov; W.Doss; N.Durier; S.Eholie; J.González; C.Gore; M.ElSayed; K.Ishii; S. M. Wasim; M.Lemoine; A.Lok; E.Kassa Lulu; M.Mizokami;
D.Ocheret; F.Okoth; J.Parry; N.Méndez-Sánchez; S.Kumar Sarin; U.Sharma;
B.Stalenkrantz;T.Swan; L.Taylor; X.Wang , J. Doyle; D.Goldberg; M.Hellard;
S.Hutchinson; L.Longworth; N.Martin; R.Morgan; E.Thomson; E.Tsochatzis;
Y.Yazdapanah.
MSF team : M. Balasegaram, R. Malpani, J. Cohn, T. Roberts, Y. Hu, J. Keenan,
J. Arkinshall, C.Perrin, P. Cawthorn, L. Menghaney, S. Gupka, A. Bozadjian, C.
Perrin,A. Loarec, M. de Souza, D. Maman, D. Donchuk, K. Herboczek , S.
Balkan, M. Berthelot, J. Goiri, C. Jamet, M. Serafini, P du Cros, MSF Egypt,
MSF Ukraine, MSF India, MSF Myanmar, MSF Iran, MSF Pakistan, MSF China,
MSF Kenya, MSF Mozambique, MSF Chad/Mali.
Liverpool University: A.Hill. Bristol University & LSHTM: P.Vickerman,
N.Martin. UNITAID team: Ph.Duneton, B.Waning,K.Timmermans.Ph.Douste
Blazy.
Geneva University Hospital team: M.Rougemont, T.Lecomte, D.Scullier, S.De
Lucia, D.Schrumpf, B. Browers, F. Negro, A. Calmy, L.Kaiser
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