Direct-Acting Antivirals with Excellent Efficacy and Favourable Safety, Represent a Unique Opportunity to Achieve HCV Elimination

The French and European Approach Towards Hepatitis C Virus Elimination

HEPDART 2017

USA

December 3rd, 2017

Tarik Asselah (MD, PhD) Professor of Medicine Hepatology, Chief INSERM UMR 1149, Hôpital Beaujon, Clichy, France. Disclosures

• Employee of Paris Public University Hospitals (AP-H P, Beaujon’s Hospital) and University of Paris

• Principal investigator for research grants : Funds paid to Hospital (AP-HP)

• Consultant, expert and speaker for: Abbvie, Bristol-Myers Squibb, Gilead, Janssen, Merck Sharp Dohme, Roche.

• Grants from : ANR, CNRS , INSERM , University of Paris, ANRS

2 The French and European Approach Towards Hepatitis C Virus Elimination

The goal of this lecture will be to present the situation of HCV in Europe and in France.

Direct-acting antivirals with excellent efficacy and favourable safety, represent a unique opportunity to achieve HCV elimination.

We will discuss the European & French approach towards Hepatitis Programs and to identify models to achieve Elimination.

The French and European Approach Towards Hepatitis C Virus Elimination

1 Great Drugs (Direct-acting antivirals)

2 Epidemiology : Europe & France

3 HCV management : Europe & France

4 Remaining Challenges

5 Take home messages Direct-acting antivirals : a Revolution

5’NTR Structural proteins Nonstructural proteins 3’NTR

Metalloprotease Envelope Serine protease RNA Capsid glycoproteins RNA helicase Cofactors polymerase

C E1 E2 NS1 NS2 NS3 NS4A NS4B NS5A NS5B

Protease Inhibitors NS5A Inhibitors Polymerase Inhibitors « …previr » « ….asvir » « …..buvir »

Telaprevir Daclatasvir Nucs Non-Nucs Boceprevir Ledipasvir Simeprevir Velpatasvir (GS-5816) Sofosbuvir Dasabuvir Paritaprevir Ombitasvir MK 3682 GS-9669 Glecaprevir Pibrentasvir ACH-3422 MK-8876 Grazoprevir Elbasvir ALS-335 Voxilaprevir MK-8408 Sovaprevir Samatasvir ACH-2684 Odalasvir (ACH-3102) Asselah et al. Liver Int 2016; 36; S1:47-57. O H3CO O H H H H3C O F F O N N NH H CH3 N O O O O N N N O N N H C NH O 3 N N N N N N O O HN P O N H O H O H O O HN O SOF O CH3 LDV H3CO VEL OCH3 VOX HO F

SOF/LDV SOF/VEL SOF + RBV ± RBV SOF/VEL/VOX ± RBV 12–24 weeks 8†–24 12 weeks 12 weeks weeks

Jan 2014 May 2014 Sept 2014 Nov 2014 Jan 2015 July 2016 July 2017

SOF + SMV SOF + DCV GRZ/EBV OMV/PTV/RTV ± RBV ± RBV ± RBV GLE/PIB ± DSV ± RBV 12–24 12–24 12–16 8–12 weeks 12–24 weeks weeks weeks weeks

PTV GLE SMV DCV GRZ

EBV PIB OMV DSV PIB

Asselah, Marcellin & Schinazi. Liver Int 2018, in press. Priorities for Direct-acting antivirals

SVR > 95% Top Priorities Safety

Tolerability Pangenotypic:

High barrier to resistance

Short duration; Low pill burden

Minimal drug–drug interactions

Access/cost

Schinazi & Asselah. From HCV to HBV cure. Liver Int. 2017;37 S1:73-80. Priorities for Direct-acting antivirals

SVR > 95% Top Priorities Safety

Tolerability High barrier to resistance

Short duration; Low pill burden Secondary Minimal drug–drug interactions Priorities

Pan-genotypic

Access/cost

Schinazi & Asselah. From HCV to HBV cure. Liver Int. 2017;37 S1:73-80. SOF/VEL (Epclusa®) for 12 weeks is highly effective across all genotypes (ASTRAL-1, ASTRAL-2 and ASTRAL-3)

2 relapses 11 2 LTFU 1 D/C relapses 1 death 1 D/C 2 D/C SVR12 (%) SVR12

1015/ 323/ 237/ 264/ 116/ 34/ 41/ 1035 328 238 277 116 35 41

• 2% of patients experienced one or more SAE; no SAEs were considered study drug related • 2 patients discontinued treatment due to AEs

Agarwal K, et al. EASL 2016; Poster #SAT-195; AE: adverse event; D/C: discontinuation; LTFU: lost to follow-up; SAE: serious adverse event Jacobson I, et al. EASL 2016; Poster #SAT-168 SOF/VEL (Epclusa®) for 12 weeks is highly effective in patients with advanced fibrosis and cirrhosis (ASTRAL 1, 2 & 3)

98 99 96 100

80 (%)

490/ 278/ 212/ Patients Patients with SVR 20 501 281 220

0 Overall Advanced Cirrhosis fibrosis

Asselah T, et al. Liver Int 2017;doi: 10.1111/liv.13534 Glecaprevir/Pibrentasvir (Maviret) in Patients with HCV GT1, 2, 4-6 Infection with or without Compensated Cirrhosis

MAVIRET for 8 Weeks in MAVIRET for 12 Weeks in TN/TE NC Patients: TN/TE CC Patients: ENDURANCE-1 and SURVEYOR-2 EXPEDITION-1

98 99 98 100 100 99 99 100 100 100 100 100 93

60 383 193 177 387 197 186 SVR12 (%) SVR12 40

20n 596 348 193 43 2 10 145 89 31 16 2 7 N 606 351 197 46 2 10 146 90 31 16 2 7 0 Overall GT1 GT2 GT4 GT5 GT6 Overall GT1 GT2 GT4 GT5 GT6 BT 1 1 Relapse 2 2 1 1 Non-VF* 7 2 2 3

All analyses are using the ITT population. TN, treatment-naïve; TE, treatment-experienced with IFN or pegIFN ± RBV, or SOF + RBV ± pegIFN; NC, non-cirrhotic; CC, compensated cirrhotic; ITT, intent-to-treat; BT, breakthrough; VF, virologic failure. *Includes patients who discontinued due to adverse events, lost to follow-up, or withdrew. MAVIRET Summary of Product Characteristics; Accessed August 2017. . Asselah T, et al. Clin Gastroenterol Hepatol. 2017 Glecaprevir/Pibrentasvir (Maviret) in Patients with HCV GT3 Infection with or without Compensated Cirrhosis

MAVIRET for 8 or 12 Weeks in MAVIRET for 12 Weeks in TN CC TN NC Patients: Patients, or 16 Weeks in TE NC/CC ENDURANCE-3 Patients: SURVEYOR-2 Part 3 95 95 97 98 100 100 96

80 80

60 60

40 40 SVR12 (%) SVR12 (%) 20n 149 222 111 20n 39 66 N N 0 157 233 115 0 40 69 MAVIRET1 MAVIRET2 DCV 3+ SOF TNTN CCCC TETE, NC/CC NC/CC 8 weeks 12 weeks 12 weeks 12 weeks 16 weeks BT 1 1 BT 1 Relapse 5 3 1 Relapse 2 Non-VF* 2 7 3 Non-VF* 1

All analyses are using the ITT population. TN, treatment-naïve; TE, treatment-experienced with IFN or pegIFN ± RBV, or SOF + RBV ± pegIFN; BT, breakthrough; CC, compensated cirrhosis; NC, noncirrhotic; DCV, daclatasvir; ESRD, end-stage renal disease; SOF, sofosbuvir; TE, treatment experienced; TN, treatment naive; VF, virologic failure. *Includes patients who discontinued due to adverse events, lost to follow-up, or withdrew. MAVIRET Summary of Product Characteristics; Accessed August 2017. Elbasvir/Grazoprevir (Zepatier): Efficacy in Different Patient Populations Phase 3 studies vs placebo 99 10 100 96 96 94 97 94 % 0 , 80

Overall mFASa 60 Treatment- SVR12 rates from experienced 40

the Phase 3 clinical SVR12 Achieving trial program 20 299 115 189 100 210 97 104 103 104 Patients Patients 312 116 198 106 217 0 Stage 4-5 OAT/PWID Comorbidity - IBLD ± HIV HIV ± HIV ± HIV CKD ± HIV Genotypes 1,4,6 1 1,4,6 1,4 1,4,6 1,4,6 1,4,6 Treatment Experience TN TN/PR-PTF TN TN/PR-PTF TN PR-PTF PR-PTF 16 Weeks 12 Weeks EBR/GZR Without RBV EBR/GZR + RBV amFAS excludes patients who failed for reasons unrelated to study medication. EBR/GZR = elbasvir/grazoprevir; SVR12 = sustained virologic response 12 weeks after the cessation of treatment; CKD = chronic kidney disease; OAT = opioid agonist therapy; PWID = people who inject drugs; IBLD = inherited blood disorders; TN = treatment naive; HIV = human immunodeficiency virus; TE = treatment experienced; RBV = ribavirin; PR = peginterferon + ribavirin; PTF = prior-treatment failure; mFAS= modified full analysis set. 1. Roth D et al. Lancet. 2015;386:1537–1545. 2. Dore GJ et al. EASL 2016, SAT-163. 3. Hezode C et al. EASL 2016, SAT-128. 4. Zeuzem S et al. Ann intern Med. 2015;163:1–13. 5. Rockstroh JK et al. Lancet HIV. 2015;2:e319–e327. 6. Kwo P et al. Gastroenterology. 2017;152:164–175. Tools for HCV screening

• Enzyme immunoassays (EIAs) – Anti-HCV antibodies – HCV core antigen

• Point-of-care (POC) tests – Rapid diagnostic tests (RDTs) – Molecular tests

• Dried blood spot (DBS) The French and European Approach Towards Hepatitis C Virus Elimination

1 Great Drugs (Direct-acting antivirals)

2 Epidemiology : Europe & France

3 HCV management : Europe & France

4 Remaining Challenges

5 Take home messages Estimated 70 Million Persons Living With HCV

Prevalence (Viremic) 0% to < 0.6% 0.6% to < 0.8% 0.8% to < 1.3% 1.3% to < 2.9% 2.9% to < 6.7%

Polaris Observatory HCV Collaborators. Lancet Gastroenterol Hepatol. 2017;2:161-176. Policies for HCV elimination Total Viremic Infections by Country (2015)

Angelos Hatzakis PHC 2017 Virus Diversity : The prevalence of the 6 different HCV genotypes varies across countries in Europe

Italy Czech Republic Germany Poland

France Russia GT 1a GT 1b GT 1 other GT 2 UK Romania GT 3 GT 4 GT 5 GT 6 Portugal Hungary

Spain Croatia • Gower E, et al. J Hepatol 2014;61:S45–57 • GT: genotype Patient’s Diversity, Prevalence of comorbidities Patient’s Diversity, Prevalence of comorbidities Alcohol: A Major Medical Need Alcohol Consumption in France Worldwide : Diagnosis and treatment rates

Estimated chronic HCV prevalence, diagnosis rate and treatment rate in 2013

6 France 5 Germany

Austria 4 England

Sweden 3 Czech Republic

Treatment rate (%) rate Treatment Egypt Spain 2 Canada Turkey Switzerland 1 Belgium Australia Portugal Denmark Brazil 0 0 20 40 60 80 100 Diagnosis rate (%) Dore GJ, et al. J Viral Hepat 2014;21(Suppl 1):1–4 Note: size of bubble depicts viraemic HCV prevalence Worldwide : Diagnosis and treatment rates

Estimated chronic HCV prevalence, diagnosis rate and treatment rate in 2013

6 France 5 Germany

Austria 4 England

Sweden 3 Czech Republic

Lancet Gastroenterol Hepatol 2017; 2: 325-336 Europe : Diagnosis and treatment rates (2015)

Lancet Gastroenterol Hepatol 2017; 2: 325-336 Number of patients with HCV infection in France: Estimation by risk group (2011)

IVDU 23 % DU, non IV 2 % Blood transfusion before ‘92 31 %

migrants 27 % Rest of the population 17 % Total population

* : données INSEE sur la population d’immigrés légaux

C Pioche, Bull Epidémiol Hebd. 2016;(13-14):224-9. Focus on HCV infections in France in 2015

Viremia prevalence : 0.29% (0.14-0.34) 200000

150000 New infections 26% 5,500 Non Diagnosed 100000 190,000 10% de la 90% SVR 74% Diagnosed 140,800 prévalence 50000

19,400 17,500 0 Infections Total Nouvellement Guéries virémiques Diagnostiquées traitées

Adapted from Razavi H et al, Lancet Gastroenterol Hepatol 2017:2, 325-36 Treatment of HCV infections in France (≈ 20,000 in 2017)

Nb of Patients Treated per months (based on 12 weeks duration per patients) Oct 2017 (Base GERS) The French and European Approach Towards Hepatitis C Virus Elimination

1 Great Drugs (Direct-acting antivirals)

2 Epidemiology : Europe & France

3 HCV management : Europe & France

4 Remaining Challenges

5 Take home messages Different screening strategies (it should be synergistic)

In populations at high risk of HCV – Prisons Risk-based testing – People with injection drugs (PWID) – Men who have sex with men (MSM) – Migrant populations

In regions/countries where the majority of patients Birth cohort testing belong to a well-defined age group

Systematic In countries with high endemicity and/or a goal of one-time testing complete elimination HCV candidates for Therapy

Public health Burden of threat disease threat

2. 3. 1. Treat high incidence Non-PWID screening and treatment Treat F3/F4 patients Prevent new infections, Elimination Prevent mortality contain the epidemic and morbidity

High incidence population Slow progression population Advanced population

Risk of onward Risk of mortality transmission and morbidity

F0 F1 F2 F3 F4

F: fibrosis stage; PWID: people who inject drugs Netherlands : National HCV/HIV treatment cascade 70% cured (n=939) / on treatment (n=49)

Treatment initiated Boerekamps et al, Clin Infect Dis 2017 (in press) Iceland : Elimination Plan

Several countries have implemented broad HCV elimination programmes

Aiming for elimination of domestic transmission of HCV by 2018 Iceland SVR rate 98% 600 554 518 500 473 464

TraP HepC 400

300

200 Major scale up of HCV testing

Number of of people Number 100 and treating • 56–70% of estimated total 0 Evaluated Treatment Completed SVR diagnosed so far initaiated treatment 45 did not complete: 1 pregnancy, 1 discontinuation due to side-effects, 43 non-compliant

Gottfredsson M, et al. AASLD 2017. abstract #1135 France : Indications for therapy : Recent evolution

• 2014 – F3-F4 (Fibrosis stage) (by any evaluation) – Extra-hepatic manifestations – HIV/HCV coinfected patients Individual Impact • 2015 (collective Impact) – F2 (Fibrosis stage) («severe» F2) • June 2016 – Transplants – Genotype 3 – At risk of contamination Collective Impact • January 2017 : Universal Treatment (& individual) AFEF Recommendations 2017 (French Association for the Study of the Liver)

• Universal access to DAAs

• Universal screening

• For all types of population including vulnerable ones

* Maladie hépatique compensée HCV Epidemiology : Modelization in France

175,000

Razavi H, Waked I, Sarrazin C, Myers RP, Idilman R, Calinas F, et al. J Viral Hepat 2014;21 Suppl 1:34-59. ANRS CO22 HEPATHER: Outcomes in patients treated with DAAs

2,156 patients (63% with cirrhosis at baseline) were followed-up for a median of 18 months Outcome incidence rates over the first 24 months after initiating DAA therapy*

Hepatocellular Carcinoma (HCC) Decompensation of cirrhosis (DC) P=0.0256 All P=0.0004 HCC incidence rates 30 36 30 † 30 Cirrhotic 33 decreased by 43% † 25 Non Cirrhotic after 12 months 20 38 20 † 34 15 33 15 † from initiation of 17 4 8 10 5 10 8 6 therapy (P=0.0256) 4 2 1 month period 6 1 month period 2 5 6 - 1 Rate per 1000 per Rate per 1000 6 - † Rate per 1000 per Rate per 1000 0 † 0 0 0 0 0 DC incidence rates 0–6 6–12 12–18 18–24 0–6 6–12 12–18 18–24 Months since initiation of therapy Months since initiation of therapy decreased by 77% after 6 months from initiation of therapy (P=0.0004) ANRS CO22 HEPATHER: Outcomes in patients treated with DAAs

2,156 patients (63% with cirrhosis at baseline) were followed-up for a median of 18 months Outcome incidence rates over the first 24 months after initiating DAA therapy*

Hepatocellular Carcinoma (HCC) Decompensation of cirrhosis (DC) P=0.0256 All P=0.0004 HCC incidence rates 30 36 30 † 30 Cirrhotic 33 decreased by 43% † 25 Non Cirrhotic after 12 months 20 38 20 † 34 15 33 15 † from initiation of 17 4 8 10 5 10 8 6 therapy (P=0.0256) 4 2 1 month period 6 1 month period 2 5 6 - 1 Rate per 1000 per Rate per 1000 6 - † Rate per 1000 per Rate per 1000 0 † 0 0 0 0 0 DC incidence rates 0–6 6–12 12–18 18–24 0–6 6–12 12–18 18–24 Months since initiation of therapy Months since initiation of therapy decreased by 77% after 6 months from Liver-related Death All Cause Death 10 10 initiation of therapy 10 (P=0.0004) 8 8 9* 8 10 6 6 5 4 Major HCV-related 4 † 1 4 10 10 5 1 4 1 outcomes decreased month period † 0 month period 2 1

6 - 2

6 - 0

Rate Rate per 1000 per 0 2 0 Rate per 1000 per Rate per 1000 after DAA-based † 0 0 0 0 0 0 0 therapy 0–6 6–12 12–18 18–24 0–6 6–12 12–18 18–24 Months since initiation of therapy Months since initiation of therapy *SOF + RBV (n=283); SOF + PEG-IFN + RBV (n=228); SOF + DCV ± RBV (n=1048) or SOF + SMV ± Carrat F, et al. EASL 2016; Poster #LBP505 RBV (n=597); †Number of events per period The French and European Approach Towards Hepatitis C Virus Elimination

1 Great Drugs (Direct-acting antivirals)

2 Epidemiology : Europe & France

3 HCV management : Europe & France

4 Remaining Challenges : Education, PWID, Migrants

5 Take home messages Control viral hepatitis by 2030 (WHO)

90% reduction in 80% of treatment- 65% reduction in new cases of chronic eligible people with chronic hepatitis B and C deaths hepatitis B and C hepatitis B and C treated

100

40 Percentage 20

0 New cases of chronic Treatment-eligible Hepatitis B and C deaths hepatitis B and C people with chronic hepatitis B and C

1. WHO. Global health sector strategy on viral hepatitis 2016-2021. June 2016. 2. WHO. SDG 3: Ensure healthy lives and promote wellbeing for all at all ages. Available at: http://www.who.int/sdg/targets/en/. WHO: World Health Organization ASCEND: Nonrandomized Phase IV Trial of HCV Treatment Outcomes by DAA Prescriber Type

• Pts (N = 600) from 13 urban, FQHCs in DC, all treated with LDV/SOF per FDA prescribing info; all providers given 3-hr training in AASLD/IDSA HCV guidance 100 89 87 84 86 80

SVR12 (%)SVR12 40

20 134/ 139/ 243/ 516/ n/N = 150 160 290 600 0 NP/PA Primary MD Specialist MD Overall

Kattakuzhy S, et al. Ann Intern Med. 2017;167:311-318. Therapeutic Patient Education: a Multidisciplinary Team (Beaujon’s Model)

Doctors

Psychologist Pharmacist

Hepatologist PATIENTS Nurses

Dietician Secretary Addiction specialists…

Boyer et al, Hepato-Gastro 2017 PWID face multiple challenges to accessing HCV treatment and care

Under-diagnosed1 Poor linkage to care2

600 100% 500 61% 387 49% of HCV-infected PWID 400 49% are undiagnosed 300 236 22% 191 in Europe 200 84 100 Number of patients Number 0 Assessed Referred to Attended Started IFN by nurse specialist appointment treatment

1. Wiessing L, et al. PLoS One 2014;9:e103345; 2. Alavi M, et al. Clin Infect Dis 2013;57:S62–9; 3. Dillon JF, et al. Hepatology, Medicine and Policy 2016;1:2 IFN: interferon PWID face multiple challenges to accessing HCV treatment and care

Under-diagnosed1 Poor linkage to care2

Patient-related barriers3 Physician and • Psychiatric co-morbidities 3 • Social difficulties system-related barriers • Negative relationships with medical and • Concerns over medication adherence and re-infection social services • Lack of collaboration between drug and HCV services • Stigmatisation • Distance of specialist HCV services

1. Wiessing L, et al. PLoS One 2014;9:e103345; 2. Alavi M, et al. Clin Infect Dis 2013;57:S62–9; 3. Dillon JF, et al. Hepatology, Medicine and Policy 2016;1:2 IFN: interferon IFN-Free DAA Therapy: Opioid Substitution Therapy vs No Opioid Substitution Therapy

No OST OS T 98 96 96 97 94 98 96 95 97 88 95 100 96 94 91

SVR12 (%) SVR12 40

20 4405 455/ 54/ 140/ 1822/ 66/ 966/ 49/ 299/ 269/ 424/ 7/ 543 40/ / n/N = 473 56 149 1882 70 984 51 316 296 437 8 /57 41 4598 0 0 OBV/PTV/RTV + OBV/PTV/RTV + LDV/SOF SOF/VEL[5] EBR/GZR[6,7] 12 Wks 8 Wks DSV + RBV[1,2] DSV ± RBV[3] + RBV[4]

SOF/VEL/VOX[8]

1. Feld JJ, et al. N Engl J Med. 2014;370:1594-1603.; 2. Puoti M, et al. AASLD 2014. Abstract 1938. 3. Grebely J, et al. EASL 2017. Abstract FRI-236.; 4. Grebely J, et al. Clin Infect Dis. 2016;63:1405-1411. 5. Grebely J, et al. Clin Infect Dis. 2016;63:1479-1481.; 6. Zeuzem S, et al. Ann Intern Med. 2015;163:1-13. 7. Dore GJ, et al. Ann Intern Med. 2016;165:625-634.; 8. Grebely J, et al. EASL 2017. Abstract FRI-235. . HCV re-infection rare

Re-infection rate in total population and among PWID (Canada)

2,5

) 1,88

- year 2,0 1,59 1,14

patients 1,5 (/100 1,0 0,48

0,5 Incidence rate Incidence 0,0 Population PWID Population PWID Spontaneous Cure after Clearance treatment (SVR)

Islam et al. AASLD 2016, A60 Integration of HCV screening in services used by PWID can improve testing rates

Clinics providing OST services may be an optimal facility for HCV testing Specialised addiction outpatient clinics,2 Multidisciplinary addiction facilities,1 Switzerland (n=1782) Amsterdam (n=497) 100 78% 66% 100 90% 50 rate (%) rate 50 testing HCV 0 rate (%) rate GP Addiction HCV testing testing HCV practice clinic 0 Addiction clinic GP practices,3 Zürich (n=387 OST)

100 91%

50 rate (%) rate HCV testing testing HCV 0 GP practice 1. Lundenburg E, et al. Eur J Gastroenterol Hepatol 2011;23:23–31; 2. Pelet A, et al. Am J Drug Alcohol Abuse 2007;33:665–74; 3. Senn O, et al. Addiction 2009;104:2033–8 OST: opioid substitution therapy Progress is needed to reduce HCV prevalence among migrants

In high-income, low-HCV prevalence countries, a substantial proportion of HCV cases are among migrants Barriers : Others PWID • Communication 28,156 HCV cases • Poor linkage to care MSM • Stigma Blood transfusion • Transient Migrants pre-1992 The Netherlands

Vriend HJ, et al. Epidemiol Infect 2013;141:1310–7; Sharma S, et al. J Hepatol 2015;63:515–22 The need to take care of all Humans, No patient left behind

Incidencerate(per100000)

Best WHO region Map key estimate Africa 31,0 America 6,4 Middle East 62,5 Europa a 61,8 South Est Asia 14,8 West Pacific 6,0 Total 23,7

Hutin J-F, Suisse, WHO, EASL 2017

Asselah et al. Eliminating Hepatitis C within Low Income Countries – the need to cure Genotypes 4, 5, 6. Journalof Hepatology, 2018 in press The French and European Approach Towards Hepatitis C Virus Elimination

1 Great Drugs (Direct-acting antivirals)

2 Epidemiology : Europe & France

3 HCV management : Europe & France

4 Remaining Challenges

5 Take home messages How to achieve HCV elimination

HCV elimination

TEST AND TREAT AWARENESS PREVENTION • HCV screening (universal) • Increase awareness • Harm reduction • Linkage to care : Treat • Fights barriers & • Infection control with optimal DAAs stigma • Blood safety • Advocacy

Asselah, Marcellin & Schinazi. Liver Int 2018, in press.