Professor Amanda Mocroft - British HIV Association · 12/12/2014 5 Rate of new HIV diagnoses, EU/EEA and WHO European Region, 1984–2013 Source: ECDC/WHO (2014). HIV/AIDS Surveillance

12/12/2014

1

in partnership

with

Institute of Epidemiology & Health

London, UK

Professor Amanda Mocroft

Five Nations Conference on

HIV and Hepatitis

The epidemiology of HIV and

viral hepatitis in Europe

Amanda Mocroft

[email protected]

12/12/2014

2

Outline

• Epidemiology of HIV, HBV and HCV across Europe

• Outcomes in coinfected persons

• Issues around late presentation for hepatitis

Outline




12/12/2014

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HIV, HBV and HCV

• All 3 are life-threatening blood-borne viruses that

affect hundreds of millions of people worldwide

• Can remain asymptomatic for many years

• Ignorance about viral hepatitis similar to early

years of AIDS; misinformation and unwillingness

to candidly address stigmatised behaviours and

social inequalities can lead to a widespread

failure to formulate cohesive public health

responses

Lazarus J et al., BMC Infectious Diseases 2014, 14(Suppl 6):S18

Transmission of viruses

Lacombe et al, Gut 2012

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The problem in WHO-Europe:

estimated total # currently infected

population HBsAg+ Chronic HCV HIV+

Total #

(mill)

% of

total

Total # (mill)

/prevalence

% of

total

Total # (mill)

/prevalence

% of

total

Total # (mill)

/prevalence

% of

total

Overall adults:

EU/EFTA 430 58 4.5 (1.0%) 34 5.5 (1.3%) 36 0.9 (0.2%) 36

Non-

EU/EFTA

300 42 8.8 (2.9%) 66 9.5 (3.1%) 64 1.5 (0.5%) 64

Total 730 100 13.3 (1.8%) 100 15.0 (2%) 100 2.4 (0.3%) 100

Globally (% from Europe): 240 mill HBsAg+ (6%), 140 mill with chronic HCV (11%), and

35 mill HIV+ (7%)

Sources: WHO, UNAIDS, ECDC, Hope et al Epidemiol Inf 2013, Razavi et al, JVH 2014

Rate of reported HIV diagnoses, by year

of diagnosis, in the EU/EEA, 1984–2013

Source: ECDC/WHO (2014). HIV/AIDS Surveillance in Europe, 2013

0

1

2

3

4

5

6

7

8

1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

Ra

te p

er

10

0 0

00

po

pu

lati

on

Year of diagnosis

Adjusted for reporting delay

Reported

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Rate of new HIV diagnoses, EU/EEA and WHO European Region, 1984–2013


New HIV diagnoses, by transmission mode and year

of diagnosis, WHO European Region, 2004–2013

Cases from Russia, Turkmenistan and Uzbekistan excluded due to inconsistent reporting during the period; cases from Estonia, Poland and Turkey excluded

due to incomplete reporting on transmission mode during the period; cases from Italy and Spain excluded due to increasing national coverage over the

period. Data are not adjusted for reporting delays and numbers of cases reported for recent years are likely to increase in future reports.


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Continuum of HIV care in Europe

0

10

20

30

40

50

60

70

80

90

100

Infected Diagnosed In care* On ART Fully

suppressed

% o

f a

ll i

nfe

cte

d

All Europe

Western E

Eastern E

*: incomplete data on number of persons in care in Eastern Europe

Percentage of patients on stable ART

0

10

20

30

40

50

60

70

80

90

100

2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

All South Central West North Central East East

Pe

rce

nta

ge

on

sta

ble

AR

T

EuroSIDA; unpublished data

Percentage on stable ART; at mid point of each calendar year, the percentage on a

single cART regimen for the previous 12 months with all (n>2) viral loads < 200 cp/ml

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European HBV prevalence

ECDC Hepatitis B and C in the EU neighbourhood; 2010

Prevalence of HBsAg by EuroSIDA region

6.8

9.7

7.3

5.0

4.9

6.1

0.0 2.0 4.0 6.0 8.0 10.0 12.0

South (N=3778)

West C (N=3664)

North (N=3862)

East C (N=1955)

East (N=2371)

Argentina (N=545)

Percentage of patients with known HCVAb status that are positive (95% C.I.)


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European HCV prevalence

Esteban et al. Journal of Hepatology 2008

Prevalence of anti-HCV by EuroSIDA region

33.3

19.5

17.8

30.3

57.4

20.3

0 10 20 30 40 50 60 70

South (N=3813)

West (N=3638)

North (N=3701)

East C (N=2034)

East (N=2549)

Argentina (N=557)

Percentage of patients with known HCV antibody status that are positive (95% C.I.)


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Range of prevalence, comparing

Hep B and C findings (systematic review)

HBsAg HCVNo of

Country

studies

Range of

prevalence

No of

Country

studies

Range of

prevalence

General population 130.1% to

5.6%13 0.4% to 5.2%

Antenatal screening 11 0.1% to 4.4% 6 0% to 1.7%

Migrants 51.0% to

15.4%. 5 0% to 23.4%

MSM 3 <1% to 4% 3 0.07% to 2.9%

PWID 21 0% to 21.3% 29 5.3% to 90%

Blood Donors (1st time) 24 0% to 5.2% 23 0.02% to 3.3%

ECDC - 2014

Key issues arising from hepatitis B and

C data collections by ECDC

• Many countries only collect data on acute hepatitis cases

• Under-reporting noted to be a major issue by some countries

• Countries provided data using a range of different case

definitions

• Difficulties with defining cases as acute or chronic

• Many cases (especially hepatitis C cases) were classified as

unknown

• Data completeness issues for many of the variables

• Discrepancy between data and findings from sero-prevalence

surveys, with reported data lower than expected in several

countries in South-eastern Europe where prevalence is highest

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Summary : Epidemiology

• Prevalence of HBV and HCV 5-6 fold higher than for HIV

– Surveillance info better for HIV than HBV / HCV

– 2-3 fold higher in Eastern than in Western region for all 3

– % of infected diagnosed higher for HIV (app 2/3) than for HBV / HCV (projected < 50%)

• Disease burden substantially larger in Eastern regions – limited access to therapy

Outline




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Cause of death in the D:A:D study 1999-2011

Smith et al Lancet 2014

3909 deaths among 49,731 pts

0

1

2

3

4

5

6

7

1999/2000 2001/2002 2003/2004 2005/2006 2007/2008 2009-2011

Ra

te o

f d

ea

th p

er

10

00

pe

rso

n-y

ea

rs

Calendar Year

Age standardised incidence rates for

specific causes of death

AIDS-related Liver-related CVD-related

Non-AIDS Cancer Other known Unknown



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Risk factors for liver related death in individuals

with HIV-1 : Coinfection with HBsAg

Thio et al Lancet 2002

From the MACS study including 5293 MSM (2734 HIV-/2559 HIV+)

326 HBsAg+ (6%), 213 (8.3%) of HIV+, 113 (4.1%) of HIV-

Coinfection with HIV/HBV and clinical events

RR 95% CI

AIDS (N=75/759) Univariate 0.98 0.78 – 1.25

Multivariate 0.86 0.63 – 1.18

All deaths (N=95/647) Univariate 1.44 1.16 – 1.79


Liver related deaths (N=18/53) Univariate 3.34 1.96 – 2.70


Konopnicki et al. AIDS 2005

9802 from 72 European HIV centres; 498 (8.7%) HBsAG +ve;

HBsAg status not related to viral/immunological responses in 1679 started cART

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Response to cART and HBV/HIV coinfection

Author Year Region CD4 changes VL response

De Luca 2002 Italy - -

Law 2004 Thailand Early, not

sustained

-

Sheng 2004 Taiwan - Increased

failure

Konopnicki 2005 Europe - -

Sheng 2007 Taiwan Lower Lower

Omland 2008 Denmark - -

Hoffmann 2009 US - -

Moore 2010 Malawi - -

Hawkins 2013 Tanzania Lower Not reported

Thio 2013 Brazil, Haiti, India, Malawi, Peru, South

Africa, Thailand, US, Zimbabwe: Kenya,

Botswana, Zambia, Uganda

- -

Chun 2014 US - -

x 1.5

HCV disease progression remains faster in

coinfected patients, despite effective ART

Lo Re et al. Ann Intern Med 2014

HCV-monoinfected patients (n=6079)

Antiretroviral-treated patients coinfected with HIV/HCV (n=4208)

0.074

0

0.1

0.2

0

Time to hepatic decompensation (years)

1 2 3 4 5 6 7 8 9 10

Cu

mu

lati

ve

in

cid

en

ce

0.048

p<0.001

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Relationship between HCV and liver related deaths

Rockstroh et al. J Hepatology 2013

13,025 HIV+ persons from Europe, 4,044 HCV+ (31%). HCV-RNA available for 2709 (67%)

1895 deaths; 218 LRD

Rockstroh et al. J Hepatology 2013

Relationship between HCV RNA and liver related deaths13,025 HIV+ persons from Europe, 4,044 HCV+ (31%). HCV-RNA available for 2709 (67%)

1895 deaths; 218 LRD

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Cumulative incidence of LRD by fibrosis

staging and CD4 cell count

Grint et al CROI 2014

145 LRD among 3941 HIV/HCV pts from EuroSIDA

Factors associated with liver related events in

EuroSIDA

0.01 0.1 1 10 100

Adjusted sub-distribution Hazard Ratio (sHR)(145 Events)

HIV Parameters

Liver-related Parameters

35<Age<45

45<Age<55

55<Age

Male

South

North

East C.

East

Argentina

CD4 Cell Count

HIV RNA

Known HCVAb+ for 2≤years<10

Known HCVAb+ for 10≤years

HCV Genotype 1/4

HBsAg Positive

F4 Fibrosis

Vs. Age<35

Vs. Female

Vs. West C.

Per Doubling

Per log10copies/ml

Vs. <2 years

Vs. <2 years

Vs. Genotype 2/3

Vs. HBsAg Negative

Vs. F0/F1 Fibrosis

Demographics

Region of EuroSIDA

F2/F3 FibrosisVs. F0/F1 Fibrosis

Grint et al CROI 2014

145 LRD among 3941

HIV/HCV pts from

EuroSIDA

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Response to cART and HCV/HIV coinfection

Author Year Region CD4 changes VL response

Greub 2000 Switzerland Lower -

Sulkowski 2002 US - -

De Luca 2002 Italy Lower -

Macias 2003 Spain Lower Not reported

Lincoln 2003 Australia Lower -

Rockstroh 2005 Europe - -

Miller 2005 Meta analysis of 8 cohort

studies/trials from Europe, US,

Canada, Australia

Lower Not reported

Seminari 2010 Italy Lower Not reported

Collazos 2011 Spain - -

Hua 2013 4 ACTG studies Lower Poorer

Summary : Outcomes

• Few changes in proportion of deaths due to liver

related events or age-standardised event rates

• Chronic HBV and HCV associated with increased

mortality and specifically liver related mortality

• HCV may be associated with poorer

immunological response following cART, evidence

for HBV more inconsistent

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Outline




Late presentation for hepatitis

• Of the estimated 2.3 million PLHIV in the European Region, 1

in 3 remain undiagnosed; only between 10% and 40% of

people with HCV in Europe are aware of their infection

• Undiagnosed HIV, HBV and/or HCV is harmful to the person

infected as appropriate health interventions are delayed

• Also detrimental to society, as persons unaware of their viral

infection may transmit to others more frequently than those

aware of their viral infection

• Late presentation associated with higher medical costs

• Need for innovative approaches to better target testing for

those at risk of being infected

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Need for definition of late presentation for

hepatitis?

• Large numbers of persons chronically infected with HBV/HCV remain undiagnosed

• Significant proportion diagnosed not linked to health care able to reliably provide comprehensive care

• Recently developed effective treatments for HBV and HCV could have greatest impact with timely diagnosis

• Consequently, a large proportion of the chronically infected enter care once they have developed clinical symptoms.

• Use of a common definition for late presenters allows comparison of surveillance data on many levels

Late presentation of viral hepatitis for medical

care : A consensus definition

HepHIV Barcelona, 2014

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Continuum of care for HBV in Greece

Papatheodoridis et al. J Viral Hepat 2014

• Telephone survey in a

representative sample of

Greek adults

• Prevalence rates age-

standardized for the Greek

adult population and

corrected for high-risk

individuals not included in

the survey

• 9974 participants

Continuum of care for HCV in USA

Yehia et al. PlosOne 2014

Meta analysis studies published 2003 – 2013;

9581 articles identified, 117 full text review and 10 included

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Summary : Late Presentation

• Late presentation remains a challenge for HIV as well as HBV and HCV

• Further work on continuum of care for both HBV and HCV needed

• Establishment of common definitions is helpful and can contribute to shape the public health response

• It will be part of the surveillance that each country undertakes as part of the governmental response to addressing HIV and viral hepatitis.

• Broad introduction of non-invasive fibrosis stage assessment will help to better characterize the hepatitis epidemic

Acknowledgements

Thanks to

Lars Peters

Jens Lundgren

Jurgen Rockstroh

Dan Grint

Colette Smith

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THANK-YOU FOR YOUR ATTENTION

0

1

2

3

4

5

6

7

1999/2000 2001/2002 2003/2004 2005/2006 2007/2008 2009-2011

Ra

te o

f d

ea

th p

er

10

00

pe

rso

n-y

ea

rs

Calendar Year

AIDS-related Liver-related CVD-related

Non-AIDS Cancer Other known Unknown

Age standardised incidence rates for

specific causes of death : Current VL < 400



12/12/2014

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Diagnosis increasing faster than treatment:

WHO European Region, 1985–2011

Sources: ECDC/WHO. HIV/AIDS surveillance in Europe 2011. Stockholm: ECDC; 2012; Federal Scientific and

Methodological Center for the Prevention and Control of AIDS, Russian Federation; Ukrainian AIDS Centre, Ukraine;

WHO/UNICEF/UNAIDS monitoring and reporting on the Health Sector Response to HIV/AIDS.

People diagnosed with HIV and receiving

antiretroviral therapy (ART) in Europe (2009-2013)

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Lower HBV viral DNA and cirrhosis

Iloeje et al. Gastroenterology 2006

N=3582 untreated HBV monoinfected Taiwanese 1991-1992,

mean FU 11 years, 365 developed cirrhosis

Risk factors for liver related death in individuals

with HIV-1 : Coinfection with HBsAg

Thio et al Lancet 2002

RR HBsAg+ versus

HBsAg-

95% CI

Age <40 7.9 3.4 – 17.8

>40 7.3 4.3 – 19.5

IDU No 8.7 4.7 – 15.9

Yes 7.5 1.9 – 26.0

Alcohol <210 10.3 5.7 – 18.7

>210 2.7 0.3 – 13.1

CD4 nadir >250 6.8 2.0 – 20.6

101-250 8.8 3.3 – 22.8

<100 11.6 4.6 – 28.7

From the MACS study including 5293 MSM (2734 HIV-/2559 HIV+)

326 HBsAg+ (6%), 213 (8.3%) of HIV+, 113 (4.1%) of HIV-

Analysis confined to those HIV+

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Mortality and liver related deaths in

HIV/HCV coinfected persons

Qurishi et al Lancet 2003

230 German pts followed 1990-2002; 93 received ARVs, 84 deaths; 25 liver related deaths

in partnership

with

21

Professor Amanda Mocroft - British HIV Association · 12/12/2014 5 Rate of new HIV diagnoses, EU/EEA and WHO European Region, 1984–2013 Source: ECDC/WHO (2014). HIV/AIDS Surveillance

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