1

Dr Huw PriceUniversity College London

17TH ANNUAL CONFERENCE OF THE

BRITISH HIV ASSOCIATION (BHIVA)

6-8 April 2011, Bournemouth International Centre

Hepatitis B virus co-infection in

HIV-infected patients in the UK

Collaborative HIV Cohort (UK CHIC)

Study

Huw Price, Loveleen Bansi, Caroline Sabin, Richard Gilson

for the UK CHIC Co-infection Group

Research Department of Infection and Population Health,

University College London

2

Background

• The prevalence of co-infection with hepatitis B virus (HBV) among the HIV-positive population in the UK is unknown

- Northern/central Europe1 9.1%

1 Konopnicki et al. Hepatitis B and HIV: prevalence, AIDS progression, response to highly active antiretroviral therapy and increased mortality in the EuroSIDA cohort. AIDS 2005; 19(6): 593-601.

2 Dienstag. Hepatitis B Virus Infection. N Engl J Med 2008; 359:1486-1500.

• BHIVA guidelines1:

– All newly diagnosed HIV+ve patients should be screened for

HBV

• HBsAg and anti-HBc and further tests as appropriate

• also with anti-HBs if not already infected

– Annual (or more frequent) anti-HBc or HBsAg test if susceptible

– Annual anti-HBs after successful vaccination

– Test for HBsAg if rise in ALT/AST (and HBV DNA if negative)

1 Brook et al. British HIV Association guidelines for the management of coinfection with HIV-1 and hepatitis B or C virus 2010. HIV Medicine 2010; 11:1–30

Background

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• Currently includes data on all HIV positive individuals

over 16 yrs old attending 13 UK centres from 1st Jan 1996

Background

• Demographics, ARV history, CD4, HIV RNA, AIDS

events, mortality, HBV, HCV

Brighton and Sussex Middlesborough

Bristol Mortimer Market Centre

Chelsea and Westminster North Middlesex

Edinburgh Royal Free

Homerton St Bart’s/Royal London

King’s College St Mary’s

Leicester

Aims

• To determine:

– HBV serology results available in UK CHIC

– Prevalence and incidence of HBV infection

– Factors associated with HBV infection

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Methods

• 12 of 13 centres in UK CHIC provided HBV data

• Trends over time summarised using latest known HBV

information at end of each year

• Cumulative prevalence of ever having a positive HBsAg

result

Methods

• Serological follow-up of positive HBsAg test results

- Chronic HBV: 2 HBsAg positive results 6 months apart

- Acute HBV: negative <6 months of first positive HBsAg

• Incidence of HBV

- Susceptible: anti-HBs negative; HBsAg & anti-HBc

negative/missing

- Incident: HBsAg or anti-HBc positive

• Associations of factors of interest identified using

regression analysis

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Patients with data in UK CHIC

N 37,331

HBsAg 25,973 69.6%

Anti-HBc 18,482 49.5%

Anti-HBs 12,637 33.9%

At least one of the above 27,450 73.5%

Factors associated with an HBsAg result being

availableHBsAg: result available not available

25973 11358

Sex Male n (%) 20045 (69.4) 7879 (77.2)

Ethnicity White n (%) 15348 (59.1) 5590 (49.2)

Black 7438 (28.6) 3447 (30.4)

Other 3187 (12.3) 2321 (20.4)

Risk group Homosexual n (%) 14770 (56.9) 3635 (32.0)

IDU 773 (3.0) 616 (5.4)

Heterosexual 7841 (30.2) 3491 (30.7)

Other 2589 (10.0) 3616 (31.8)

Year of cohort 1996-1999 n (%) 9323 (35.9) 4743 (41.8)

entry 2000-2004 8290 (31.9) 2749 (24.2)

2005-2010 8360 (32.2) 3866 (34.0)

Age at entry Median (IQR) 35 (30, 40) 35 (30, 41)

CD4 at entry Median (IQR) 340 (173, 515) 300 (129, 490)

VL at entry Median (IQR) 18300 (1346, 94700) 12899 (606, 83200)

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Trends over time (1)

0

5000

10000

15000

20000

25000

97 98 99 00 01 02 03 04 05 06 07 08 09

N

Year

Total

under

follow-up

Patients

with any

HBV data

Trends over time (2)

0%

20%

40%

60%

80%

100%

97 98 99 00 01 02 03 04 05 06 07 08 09

Year

Susceptible

Unexposed

(possibly vaccinated)

Immune

(vaccinated)

Immune

(vaccine or infection)

Immune

(natural infection)

Isolated anti-HBc

Currently infected

(HBsAg+ve)

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Interpretation of available HBV results

HBsAg Anti-HBs Anti-HBc

Susceptible – – –

Immune Vaccinated – + –

Cleared infection – + +

Unknown – +

Infected +

Isolated anti-HBc – – +

Unexposed – –

Interpretation of available HBV results

HBsAg Anti-HBs Anti-HBc

Susceptible – – –

Immune Vaccinated – + –

Cleared infection – + +

Unknown – +

Infected +

Isolated anti-HBc – – +

Unexposed – –

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Trends over time (2)

0%

20%

40%

60%

80%

100%

97 98 99 00 01 02 03 04 05 06 07 08 09

Year

Susceptible

Unexposed

(possibly vaccinated)

Immune

(vaccinated)

Immune

(vaccine or infection)

Immune

(natural infection)

Isolated anti-HBc

Currently infected

(HBsAg+ve)

Last known status at end-2009

14%

23%

19%3%

30%

4%

7%Susceptible

Unexposed

(possibly vaccinated)Immune

(vaccinated)Immune

(vaccine or infection)Immune

(natural infection)Isolated anti-HBc

Currently infected

(HBsAg+ve)

9

Last known status at end-2009

Last known status at end-2009

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Prevalence of HBsAg

Patients with HBsAg result 25,973

Patients with positive HBsAg result 1,781

Cumulative prevalence 6.9% (95% CI: 6.6–7.2)

Multivariate

OR (95% CI) P-value

Ethnicity White 1 <0.0001

Black 2.53 (2.05, 3.12)

Other 1.73 (1.39, 2.14)

Risk group Homosexual 1 <0.0001

Heterosexual (f) 0.43 (0.34, 0.55)

Heterosexual (m) 0.87 (0.69, 1.09)

IDU 1.45 (0.95, 2.20)

Other 0.66 (0.51, 0.86)

Year of cohort 1996-1999 1.74 (1.44, 2.11) <0.0001

entry 2000-2004 1.29 (1.10, 1.50)

2005-2010 1Age at entry Per 10 years older 1.01 (0.93, 1.09) 0.88

CD4 at entry Per 50 cells higher 0.94 (0.93, 0.96) <0.0001

VL at entry Per 1 log higher 0.93 (0.88, 0.98) 0.01

Factors associated with positive HBsAg

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Follow-up of HBsAg-positive patients

N 1,781

Chronic HBV 836 46.9%

Acute HBV 187 10.5%

Unclassifiable 758 42.6%

Incidence of HBV

Patients initially HBV susceptible 3,379

Incidence of HBV ( / 100 pt yrs) 1.7 (95% CI: 1.5–1.9)

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Incidence by risk factor

0.45 0.43

0.62

1.71

0.52

0.1

1

10

Male Female MSM Hetero-

(female)

Hetero-

(male)

IDU Other

Un

ad

just

ed

rate

ra

tio

s

Incidence of HBV by sex and risk group

Summary and discussion

• Cumulative prevalence of HBV: 6.9%

• Incidence of HBV: 1.7 / 100 patient years

• Further analyses will examine HBV and HIV disease

outcomes in co-infected individuals

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Acknowledgements

UK CHIC Co-infection Subgroup: Loveleen Bansi, Sanjay Bhagani, Andrew Burroughs, David Chadwick, Emma

Devitt, David Dunn, Martin Fisher, Richard Gilson, Janice Main, Mark Nelson, Deenan Pillay, Alison Rodger, Caroline

Sabin and Chris Taylor

UK CHIC Steering Committee: Jonathan Ainsworth, Jane Anderson, Abdel Babiker, Loveleen Bansi, David

Chadwick, Valerie Delpech, David Dunn, Martin Fisher, Brian Gazzard, Richard Gilson, Mark Gompels, Teresa

Hill, Margaret Johnson, Clifford Leen, Mark Nelson, Chloe Orkin, Adrian Palfreeman, Andrew Phillips, Deenan

Pillay, Frank Post, Caroline Sabin (PI), Memory Sachikonye, Achim Schwenk, John Walsh.

Central Co-ordination: Loveleen Bansi, Teresa Hill, Andrew Phillips, Caroline Sabin (UCL Medical School); David

Dunn, Adam Glabay (Medical Research Council Clinical Trials Unit [MRC CTU])

Participating Sites:Research Department of Infection and Population Health, UCL Medical School: C Sabin, T Hill, L Bansi, A Phillips, S Huntington

Medical Research Council Clinical Trials Unit (MRC CTU): A Babiker, D Dunn, A Glabay, K Porter

Brighton and Sussex University Hospitals NHS Trust : M Fisher, N Perry, S Tilbury, D Churchill

Chelsea and Westminster NHS Trust: B Gazzard, M Nelson, M Waxman, D Asboe, S Mandalia

Kings College London School of Medicine, GKT Hospitals: F Post, H Korat, C Taylor, Z Gleisner, F Ibrahim, L Campbell

Mortimer Market Centre, UCL Medical School: R Gilson, N Brima, I Williams

Royal Free NHS Trust/UCL Medical School: M Johnson, M Youle, F Lampe, C Smith, H Grabowska, C Chaloner, D Puradiredja

Imperial College Healthcare NHS Trust: J Walsh, J Weber, F Ramzan, N Mackie, A Winston

Barts and the London NHS Trust: C Orkin, N Garrett, J Lynch, J Hand, C de Souza

Homerton University Hospital NHS Trust: J Anderson, S Munshi

The Lothian University Hospital NHS Trust: C Leen, A Wilson

North Middlesex University Hospital NHS Trust: A Schwenk, J Ainsworth, C Wood, S Miller

Health Protection Agency Centre for Infections: V Delpech

North Bristol NHS Trust: M Gompels, S Allan

University of Leicester NHS Trust: A Palfreeman, A Moore

South Tees Hospitals NHS Foundation Trust: D Chadwick, K Wakeman

Funding: UK CHIC is funded by the UK Medical Research Council

www.ukchic.org.uk