friday, july 17 – saturday, july 18, 2015 sheraton wall ... july 17 – saturday, july 18, 2015 ....

Theme - HIV/Viral Hepatitis: Antiviral Therapy Development and Access

For more information and to register, visit: coinfectionmeeting.com

Friday, July 17 – Saturday, July 18, 2015 Sheraton Wall Centre, Vancouver, Canada

PHOTO BY JAMESZ_FLICKR

www.iasociety.org

Highlights from the Meeting

• Only international meeting that brings together all the stakeholders in HIV/Hepatitis Coinfection to work towards equitable access to Hepatitis therapy globally – Review latest science – Identify barriers – Learn from recent successes in low middle and

high income countries – Engage all partners in constructive solutions

HCV treatment revolution

2.2% have treatment (WHO 2014)

World Hepatitis Alliance

Change the mindset

• Challenge the prevailing mindset such that viral hepatitis joins HIV, malaria and tuberculosis as the most important infectious diseases

• Funders, government officials, NGOs, medical societies, foundations, man-in-the-street

• Advocacy is key - 240 million people who are

chronically infected with HBV (plus 130 million HCV), if only a fraction could be empowered to respond…

Improving the cascade of care

Diagnosis Access

Treated SVR

Modeled data for non-VA US population

Yehia PLoS One 2014

8

Cost of screening can be calculated in different populations

Müllhaupt B, Bruggmann P, Bihl F, et al. Modeling the health and economic burden of hepatitis C virus in Switzerland. PLoS ONE 2015; 10.

Example: Switzerland

Birth Cohort

General 40-44 years 50% of cases 75% of cases (1924-2013) (1969-1973) (1959-1978) (1949-1983)

Prevalence and diagnosis rates Anti-HCV prevalence 1.3% 2.3% 2.2% 2.1% HCV RNA prevalence 1.0% 1.8% 1.8% 1.6% Diagnosis Rate 40% 40% 40% 40% Number of tests required to identify 1 viremic case to treat (n) Anti-HCV 158 92 94 101 HCV RNA 1.3 1.3 1.3 1.3 Genotype 1 1 1 1 Associated costs to identify 1 viremic case, by test type (CHF) Anti-HCV 3,939 2,295 2,357 2,531 HCV RNA 226 226 226 226 Genotype 180 180 180 180 Total 4,345 2,701 2,763 2,937

The favorable safety profiles of new DAA combinations suggest that minimal laboratory monitoring will be necessary to assess safety during treatment. Diagnostics and monitoring could be limited to: - two HCV antigen tests to confirm chronic infection before treatment and clearance after treatment (detection limit HCV RNA >2000 IU/mL: US$34 for two tests - two full blood counts + clinical chemistry tests (ALT / creatinine): US$22 - genotyping if necessary: US$90 (not needed if treatment is pan-genotypic)

Simplified diagnostic testing for HCV

10

Treatment Rate by Country, 2013

Razavi H, Waked I, Sarrazin C, Myers RP, Idilman R, Calinas F, et al. The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm. J Viral Hepat 2014;21 Suppl 1:34-59.

Hatzakis A, Chulanov V, Gadano AC, Bergin C, Ben-Ari Z, Mossong J, et al. The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm – J Viral Hepat 2014. Submitted for publication 30 July 2014.

11

HCV Diagnosis Rate, Treatment Rate and Prevalence

Wedemeyer H, Dore GJ, Ward JW. Estimates on HCV disease burden worldwide - filling the gaps. J Viral Hepat 2015;22 Suppl 1:1-5.

12

HCV burden among PWID in LMICs

10 out of 16 million PWIDs have anti-HCV antibodies (Nelson, Lancet, 2011) more than 5% of the HCV+ are PWIDs globally

PWID-HCV+: 26% live in East/SouthEast Asia and 23.5% in Eastern Europe (Nelson, Lancet, 2011)

25.6% PWIDs

21.5% PWIDs

40.4% PWIDs

5.6% PWIDs

2.7% PWIDs

0.14 million

1.1 million

4.1 million

0.64 million

1.4 million

PWID Not PWID Number of adults with HCV antibodies % of PWIDs

Georgia

Ukraine

Russia

Myanmar

Indonesia

Vietnam

(adapted from Luhmann et al. IJDP. forthcoming)

2.7 million 9.2% PWIDs

2nd International HIV/Viral Hepatitis Co-infection Meeting IAS Vancouver 2015

13

Use of non-sterile equipment needs to be eliminated

Hutin YJ, Hauri AM, Armstrong GL. Use of injections in healthcare settings worldwide, 2000: literature review and regional estimates. BMJ 2003;327:1075.

Potential role of addiction care

Testing, awareness and counseling

Evaluation, retention and adherence

Prevention of reinfection

15

Increasing treatment and SVR can significantly reduce the number of viremic infections

-

50,000

100,000

150,000

200,000

250,000

300,000

Total Infected Cases (Viremic) - Germany

Basecase Increased Efficacy Only Increased Efficacy & Treatment

-

50,000

100,000

150,000

200,000

250,000

Total Infected Cases (Viremic) - France


-

1,000,000

2,000,000

3,000,000

4,000,000

5,000,000

6,000,000

7,000,000

Total Infected Cases (Viremic) - Egypt


-

1,000,000

2,000,000

3,000,000

4,000,000

5,000,000

6,000,000

7,000,000

Total Infected Cases (Viremic) - Russia

Base Case Increased Efficacy Only Increased Efficacy & Treatment

16

Increasing treatment and SVR can significantly reduce the disease burden

-

200

400

600

800

1,000

1,200

1,400

1,600

1,800

Liver-related Deaths - Germany


-

200

400

600

800

1,000

1,200

1,400

1,600

1,800

Liver-related Deaths - France


-

5,000

10,000

15,000

20,000

25,000

30,000

35,000

40,000

Liver-related Deaths - Egypt


-

2,000

4,000

6,000

8,000

10,000

12,000

14,000

16,000

18,000

Liver-related Deaths - Russia

Base Case Increased Efficacy Only Increased Efficacy & Treatment

Toranomon Hospital cohort: reduction in HCC incidence with ETV greater among cirrhotic patients

Hosaka T, et al. HEPATOLOGY 2013;58:98-107

1 3 5 Treatment duration (years)

50

40

30

20

10

0

0

Cum

ulat

ive

HCC

rate

(%)

Cirrhosis

Log-rank test: P<0.001

79 85 85

79 72 76 65

53 35 54 47

17 ETV Control

No at risk

50

40

30

20

10

0

0 1 3 5

Log-rank test: P=0.440

No Cirrhosis

1.6% 3.6%

2.5% 0%

237 231 231

237 192 201 181

132 66 169 143

27

Control

ETV

ETV Control

No at risk

Treatment duration (years ) Cu

mul

ativ

e HC

C ra

te (%

)

20.9%

4.3%

38.9%

7.0%

Control

ETV

18

Barriers to HCV treatment

(Wolfe et al. Special issue on HCV and drug use. IJDP. forthcoming)

2nd International HIV/Viral Hepatitis Co-infection Meeting IAS Vancouver 2015

Data from Global Burden of Disease report, 2013. Lancet January 10th 2015, 385: 117-171 FDA Orange Book. http://www.accessdata.fda.gov/scripts/cder/ob/default.cfm. Infographic by TAG.

http://www.accessdata.fda.gov/scripts/cder/ob/default.cfm

5g of daclatasvir 12 weeks of treatment, 60mg/day Cost = $53,000 (UK price)

5g of diamonds 25 1-carat ($1900 each) Cost = $48,000

Daclatasvir: generic prices

Cost of API = $10,000/kg

API per 12 weeks = $50

Formulated drug = $70

Packaged drug = $71

Final generic Price = $107

API needed per person = 5g (60mg x 84 days)

Formulation = 40%

Packaging = $0.35/month

Profit margin = 50%

For mid 2015, Prices falling rapidly

The ideal DAA treatment: low cost, ≥90% SVR, pan-genotypic, short duration, well tolerated

0

10

20

30

40

50

60

70

80

90

100

1 2 3 4 5 6

Genotype

Perc

ent S

VR

≥90% ≥90% ≥90% ≥90% ≥90% ≥90%

n≥50 n≥50 n≥50 n≥50 n≥50 n≥50 G1 G2 G3 G4 G5 G6

Sofosbuvir + Daclatasvir ± RBV (12 or 24 weeks)

Sources: A1444040 trial; ALLY-1; ALLY-2; ALLY-3; 3 French EAPs

525/556 193/216 47/50 1/1 1/1 52/56

Registration status worldwide of Sovaldi® and Daklinza®

High income countries

Countries where Sovaldi® is registered

Countries where Daklinza® is registered

Countries where Daklinza® & Sovaldi® are registered

BUT G3 Remains a Concern in the Real World TRIO: 24 Wks SOF + RBV for GT3 HCV in Real-World Settings

18 academic and 17 community practices in US TRIO network 24 wks sofosbuvir + RBV (N = 96)

ITT population: n = 96; PP population (completed therapy with SVR12 data): n = 77

Key baseline characteristics Male: 56%

HCV RNA > 6 x 106 IU/mL: 15%

Cirrhosis: 30%

Previously treated: 39%

2/96 pts died from causes not related to treatment

Kowdley K, et al. EASL 2015. Abstract P0867.

SVR

12 (%

)

Overall

Tx-Naive, Noncirrhotic

Tx-Expd, Cirrhotic

PP

100 80 60 40 20

0 ITT

70 87

100 80 60 40 20

0 ITT

73 94

PP

100 80 60 40 20 0

ITT

57 80

PP

77 N = 96

34 N = 44

10 N = 14

Selection of RAVs in Patients who Failed after LDV (no SOF)

16% (12/76)

84% (64/76)

Before LDV Treatment

99% (72/73)

1%

At Virologic Failure With LDV Treatment

Patients without NS5A RAVs Patients with NS5A RAVs

Patients who failed after a ledipasvir-containing treatment

(without sofosbuvir)

(Dvory-Sobol et al., EASL 2015)

The NS5A RAVs are Persistent 24 Wks LDV/SOF After Failure of LDV/SOF-Based Therapy: Effect of Baseline RAVs

NS5B variants emerged during retreatment in 33% of pts (4/12) with virologic failure – S282T: n = 2; L159F: n = 1; S282T + L159F: n = 1

Lawitz E, et al. EASL 2015. Abstract O005.

SVR12 by Baseline NS5A RAVs, n/N (%) LDV/SOF for 24 Wks Number of RAVs 0 11/11 (100) 1 11/16 (69) ≥ 2 7/14 (50)

Single NS5A RAV Q30R or M28T 5/5 (100) L31M 4/5 (80) Y93H/N 2/6 (33)

Treatment volumes increasing

Liver Clinic

Make sure you have the capacity to treat & follow everyone

Clinic Issues • Matching needs of your population

– Setting (hospital vs clinic vs the street) – Support services (social work, addiction

counseling) • Triage

– Who gets treated first? • Paper work

– Without systems in place…you will drown! • Following patients on treatment

– Capacity (MD/RN/other), frequency, liver disease

30

HCV in Mongolia

• Genotype 1b (98%) • Anti-HCV average 9.8-15% (285,700-450,000 people)

» Elder people up to 33%

» Health workers >50% co-infected HCV and HBV

» 82% reported needle-stick injuries in 2008

• Viremic 6.8-11% (210,000-330,000 people) • Diagnosed ever: 60,000 (1300 new diagnoses 2013)

» Liver biopsy: 40-60/year (mainly for HCC); Fibroscans: >3000

• Treated (PEG/RBV): 200; DAAs: happy few • Liver transplants: 8 (of which 3 due to HCV) • LC >>350/100,000 many undiagnosed • 15% of all mortality due to LC/HCC (2nd cause of death, esp. in 40-65 age

group) • HCC mortality: 63.2/100,000; world record, 8x world average

18/07/2015 Mongolia - how to stop the HCV epidemic?

30

Mongolia

31

Mongolia - latest actions

• New guidelines for treatment of HCV approved

• 100 “Hep-C frontline” doctors trained (in capital & 21 provinces)

» SOF + LDP roll-out expected Nov 2015 ($400/month)

» Generic tenofovir now available $25/m for HBV+ pregnant women

• Dialogue on financing options for hepatitis care & treatment

» Standard package of services for hep C and B?

» Economic analysis of hep C and B care and treatment

• Discussing new National programme on viral hepatitis (not only HCV)

• Website to link providers, patients, labs and the NCCD for hepatitis screening, care and treatment patients.

18/07/2015 Mongolia - how to stop the HCV epidemic? 31

• Team building & teamwork – Ministry of Health Brazilian Health Surveillance Agency (Anvisa) Secretariat of Health Surveillance (SVS/MS) Secretariat of Science, Technology and Strategic Inputs (SCTIE/MS) – Organized Civil Society, – Healthcare providers

GOAL

TREAT 60,000 PEOPLE IN THE NEXT TWO YEARS.

Lessons Learned in Decision Making

Perspectives July 2015 Onward

Sustained Virological Response (SVR)

Population with Treatment Recommended

Treatments/year

PR/PR+BOC/TEL (2013-2015)

INTERFERON-FREE SOF+DAC/SIM

(2015-) 40%

15.000

F3/F4 (F2)*

>90%

F3/F4 (F2), HIV, Pr/P Tx... 30.000

1. New funding for HCV treatment to be established at either national or international level, to allow large drug orders to be made, and these economies of scale to be achieved.

2. Clear and transparent treatment access policies with voluntary licensing, from all companies making DAAs (BMS, Merck, AbbVie)

3. Feasibility studies of DAA combinations in LMICs to prove this can be done cheaply

4. Low cost point of care tests to monitor viral load or antigen

What needs to happen?

Cycle of Action

ADVOCACY

Action

Awareness

Priority

Funding

Response & Data

36

In the next 25 years, HCV can be eliminated

New HCV Infections

Cured Mortality

New HCV Infections

Cured Mortality

Today Future

friday, july 17 – saturday, july 18, 2015 sheraton wall ... july 17 – saturday, july 18, 2015 ....

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