HCV response to treatment in IDUs (PWID) in the

Czech Republic

Vratislav RehakRemedis Clinic, Prague, Czech Republic 1

Institute of Public Health “Dr. Milan Jovanovic Batut”Belgrade, SerbiaMay 24, 2014

Czech Republic and drug use

Population of CR 10 000 000

„Problematic“ drug users (EMCDDA) 40 200of them

- injecting drug users 38 600

- opiate users 9 300

- metamphetamine users 30 900

Office of the Government (2012) - data from the year 2011

Czech Republic - HCV prevalence

In general population < 0.2 % In IDU‘s ≈ 30% Overall prevalence 0.3 %

Very low prevalence of HIV IDU‘s

Zabransky T, Mravcik V, Korcisova B, Rehak V. Hepatitis C Virus Infection among Injecting Drug Users in the Czech Republic - Prevalence and Associated Factors. European Addiction Research 2006; 12:151-160

HIV/AIDS, Czech Republic

1985 – 31.12.2012

HIV + cumulatively 1887M 1554 (82,4 %) F 333 (17,6 %)

of them

developed AIDS 366of them

died 187

4

5

6

7

Hepatitis C – notified cases in the Czech Republic 1993 - 2012

Remedis – Program of Comprehensive Care

Goal: to concentrate all available „drug“ services in one place to promote effectiveness of interventions and patient compliance including adherence to antiviral treatment

On site available services

Medical careInternal medicine, gastroenterology, hepatology (incl. liver biopsy), surgery, gynecology, primary care, X-ray, …

Psychiatry, clinical psychology Easy to reach referrals BBD, STD, TB testing Counselling (psychosocial, harm reduction) Opiate substitution treatment Psychotherapy (group or individual) Social work Established collaboration with harm reduction

centers in Prague

10

Study design – inclusion criteria

Prospective recruitment 2003 – 2010 in single center – Remedis Prague, Czech Republic

Proven chronic hepatitis C based on standard serological and histological criteria with detectable HCV RNA

History of past or current IDU

Psychosocially stabilized and motivated patient (including those on OST)

Individualized assessment of eligibility and suitability for antiviral therapy in multidisciplinary setting

No other selection, restriction or limitation to Tx

All efficacy analyses were conducted on →Modified intent-to-treat population – included are all subjects who received at least 1st dose of medication

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Duration of IDU career (years)less than 1

8%

1 to 210%

3 to 531%more than 5

36%

more than 1015%

OPIATES 59%

METH37%

THC1%

cocain0%

other2%

Self reported „main drug“

Study population

n = 345 Male : female – 204 : 141

(59:41%) Average age – 28.4 (17-53)

Males 29.6 (19-52) Females 26,5 (17-53)

Body weight males 78.1 (51-125)

median 77 females 63.1(44-130)

median 60

HCV clinical characteristics ALT WNL – 26%

Male : female - 24.4% : 27.4%

HCV documented d.uration – 3.83 years (0.5 – 17 years)

Treatment naive patients No coinfections

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HCV genotypes – 1 vs. non-1

G 1 (4)70%

G 2/329%

UNK 1%

G 115%

G 1a14%

G 1a/1b1%

G 1b43%

G1b/4a1%

1b/3a0%

20%

2a/2c1%

30%

3a28%

40% UNK

1%

HCV subtypes

Stage 0 Stage 1 Stage 2 Stage 3 Stage 4 Stage 5 Stage 6 UNK0

20

40

60

80

100

120

140

Histological stage (modif. Ishak)

OST YES41%

(of them 6% for drug relaps)

OST NO59%

Opiate substitution treatment while on HCV therapy

PEG IFN + RBV in chronic HCV – published dataPEG IFN alfa-2b PEG IFN alfa-2a PEG IFN alfa-2a

Author: Manns et al.Lancet 2001

Fried et al.NEJM 2002

Hadzianys et al.J Hepatol 2002

Dose: 1.5 mcg/w + 800 mg/d RBV

180 mcg + 1000-1200 mg/d

RBV

180 mcg + 1000-1200 mg/d RBV

SVR total (%) 54 56 61SVR genotype 1 (%) 42 46 51

Prediction factors of SVR Viral factors

genotype viral load (HCV RNA),

Host (biological) factors age up to 40 years histology – fibrosis (stage), absent steatosis duration of the disease (infection) body weight (BMI) race HIV coinfection compliance / adherence to Tx

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Pre-treatment follow-up

Mean 14,2 months (0-72 months)

Prior dependency stabilization

Psychosocial stabilization

Other relevant interventions accomplished

Treatment regimen - standard

Pegylated interferon alfa weekly

+ Ribavirin 800-1200 mg/d weight based

Genotype 1 - 48 weeksGenotype 2,3 – 24 weeks

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Results obtained - table

RVRweek 4

EVRweek 12

ETRweek 24/48

ITT - SVRweek 24F/U

Genotype 1(4) non-1 1(4) non-1 1(4) non-1 1(4) non-1

HCV RNA negative

131(55.0%)*

82(82.8%)*

212(88.7%)*

94(94.0%)*

215(89.2%)*

86(85.1%)*

195(80.9%)ITT

85(84.2%)ITT

HCV RNA positive

97 13 21 2 7 3 26 6

result not available

8 4 3 2 9 6 0 0

lost to F/U 3 0 3 0 10 6 21 10

Total 239 99 239 100 241 101 242 ** 101 **

RVR – rapid virological response, EVR – early virological response, ETR – end of treatment virological response, F/U - follow-up*data based on results available in particular period of therapy -not ITT, **2 subjectt with unknown genotype

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On-treatment virological responses in genotypes 1(4) patients

(included are only patients with available results in particular weeks

– not ITT)

RVR-week 4 EVR-week 12 ETR-week 48

RVR YES (55%)

RVR NO

EVR YES (83%)

EVR NO

ETR YES (89%)

ETR NO

n=239 n=239 n=241

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Sustained virological response, genotypes 1(4) – week 24 of F/U

ITT population

SVR YES 195(80.9%)

SVR- NO 26(10.6%)

Lost to follow-up 21(8.5%)

n=128

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On-treatment virological responses in non-1 genotypes (3, 2) patients

(included are only patients with available results in particular weeks

– not ITT)

RVR-week 4 EVR-week 12 ETR-week 24

RVR YES 82 (83%)

RVR NO

EVR YES 94 (94%)

EVR NO

ETR YES86 (85%)

ETR NO

n=99 n=100 n=101

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Sustained virological response, GENOTYPES non-1 (3, 2)

– week 24 of F/U

ITT population

SVR YES 85(84,2%)

SVR- NO 6 (5.9%)

Lost to follow-up 10 (9.9%)

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Sustained virological response, ALL GENOTYPES – week 24 of F/U

ITT population

SVR YES 282

(81.7%)

SVR- NO 32 (9.3%)

Lost to follow-up 31 (9.0%)

Adverse events observed

Mood disorders 45,3%

Thyroid disorders 18,3%

Ribavirin dose reduction due to anemia 13,3%

AE‘s were managed individually, not á la carte

Adverse events frequency was generally comparable or lower than published elsewhere

Reinfection rate(data not updated)

3 years standard F/U in 76% of patients

2 reinfection documented Frequency of 0.6% per person/year 1 reinfection after 5 years

Reasons for good treatment response

Low age and short duration of HCV infection

Early stages of HCV infection (low fibrosis)

Low body weight (BMI) Low somatic comorbidity Good adherence / compliance →

comprehensive care setting in Remedis HCV antiviral Tx is an integral part of

addiction treatment HCV antiviral therapy is considered as one

of the steps of an addicted patient recovery

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Conclusions Chronic hepatitis C in certain settings can be

nearly fully treatable disease even with current standard of therapy

IDU‘s can be successfully treated with higher than average efficacy

HCV antiviral therapy should optimally be initiated and performed within a comprehensive service setting promoting good adherence

HCV antiviral therapy can be one of the most powerful preventative measure in low prevalence countries such as the Czech Republic

The cost-effectiveness of HCV antiviral treatment for injecting drug user populations

Natasha K. Martin1,2,*,†, Peter Vickerman1,2, Alec Miners2, Graham R. Foster3, Sharon J. Hutchinson4,5, David J. Goldberg4, Matthew Hickman1

DOI: 10.1002/hep.24656

Abstract

Background & Aims: Injecting drug use is the main risk of hepatitis C virus transmission in most developed countries. HCV

antiviral treatment (peginterferon-α+ribavirin) has been shown to be cost-effective for patients with no reinfection risk. We examined the cost-effectiveness of providing antiviral treatment for injectors (IDUs) as compared to treating ex/non-IDUs or no treatment.

Methods: A dynamic model of HCV transmission and disease progression was developed, incorporating: a fixed

number of antiviral treatments allocated at the mild HCV stage over 10 years, no retreatment after

treatment failure, potential reinfection, and three baseline IDU HCV prevalence scenarios (20%, 40%, and 60%). We performed a probabilistic cost-utility analysis estimating long-term costs and outcomes measured in Quality Adjusted Life Years (QALYs) and calculating the incremental cost-effectiveness ratio (ICER) comparing treating IDUs, ex/non-IDUs or no treatment.

Results: Antiviral treatment for IDUs is the most cost-effective option in the 20% and 40% baseline chronic

prevalence settings, with ICERs compared to no treatment of £521 and £2,539 per QALY saved, respectively. Treatment of ex/non-IDUs is dominated in these scenarios. At 60% baseline prevalence treating ex/non-IDUs is slightly more likely to be the more cost-effective option (with an ICER compared to no treatment of £6,803), and treating IDUs dominated due to high reinfection. A sensitivity analysis indicates these rankings hold even when IDU sustained viral response rates as compared to ex/non-IDUs are halved.

Conclusions: Despite the possibility of reinfection, the model suggests providing antiviral

treatment to IDUs is the most cost-effective policy option in chronic prevalence scenarios less than 60%. Further research on how HCV treatment for injectors can be scaled up, and its impact on prevalence is warranted. (HEPATOLOGY 2011.)

Seroprevalence study in prisons in the Czech Republic 2009-2012

Total inmates tested 971 Results – 2 HIV + (0,2%)

1 HIV+ , HCV+ 1 HIV + , HCV-

274 HCV + (28,12%)

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Opportunity for prevention of HCV? Prisons! In many countries a considerable gap in testing is in

incarcerated populations. Prisons provide an excellent opportunity to diagnose and

treat the largest known reservoir of infected individuals and provides the single most effective HCV public health strategy.

Intake testing and councelling should be mandatory, treatment should be made available based on the patients will and local conditions.