1. Acute HCV in HIV-infected Men The ‘new’ STD
Dr Emma Page
Clinical Research Fellow
Imperial College London
Chelsea and Westminster Hospital

2. Increase in acute HCV infections amongst HIV+12 10 8
Incidence of acute HCV
infection/1000 pt yrs 6 4 2
1997
1998
1999
2000
2001
2002
2003
Test for trend p-value using Poisson regression p<0.001
Error bars = 95% CI
Browne RE, et al. 2nd IAS 2003; Abstract 972

3. Reports of acute hepatitis C in HIV+ MSM4 1 7 5
2,3 6
1. Giraudon I et al. STI 2007;84: , 2. Ghosn et al. STI 2006; 82: ; 3. Gambotti et al. Euro Surveill 2005; 10: ; 4. Gotz et al. AIDS 2005; 19: Vogel M et al. J Viral Hepat 2005; 12: ; 6. Matthews GV AIDS 2007;21: ; 7 Luetkemeyer A et al. JAIDS 2006;41:31-36

4. Increased AHC or increased testing?
Number longitudinal studies in HIV+ MSM:
London & Brighton1:
2000 < 0.1/100 py; /100 py; /100 py
Clinics with greatest annual increase had routine screening throughout study period
UK – PHI2
: n=155; 3mnthly HCV Ab
0% 1999 to 2002 / 2.5% 2004 / 3.9% 2006
ACS3
; n=514
/100 py vs /100 py
1. Giraudon I et al. STI 2007;84: , 2. Fox J et al. AIDS 2008;22: , 3.van de Laar T et al. JID 2007;196:

5. HCV: SNAHC Surveillance of Newly Acquired HCV
London and South East (22 sites)
2008: prospective and retrospective
2006 & 2007 n = 200 / 2008: n = 40
All men
All MSM
Median age 38 (range 19-62)
94% HIV + (all on ARVs, median CD4 540)
63% born in UK, 89% white ethnicity

6. HCV: SNAHC Surveillance of Newly Acquired HCV
Risk factors:
Drug taking:
IDU 16% (7% last 6 mnths)
Non-IDU 60% (C 39%, K 27%, Cystal 20%, E 18%)
Sexual
STI 63% (31% early STS, 22% chlamydia)
UPAI 83% (75% UPIAI, 73% UPRAI)
Fisting 22% (69% UPIF, 65% UPRF)
Sex & drugs 90%

7. Chronic hepatitis C routes of transmission

8. Sexual transmission ?

9. Seroprevalence studies: heterosexual couples
n Partner HCV Concordant Ab+ve Genotype Akahane Japan (1994) % 24% Chayama Japan (1995) 295 9% 5% Kao Taiwan (1996) % 11% Neumayr Austria (1999) 80 5% 2.5% Sun Taiwan (1999) % 3% Stroffolini Italyn (2001) % 6% Terrault USA (2003) % 2.7%

10. Incidence of HCV: sero-discordant heterosexual couples
F/U n incidence
(years) (per year)
Piazza Italy (1997) n/a %
Kao Taiwan (2000) %
Marincovich Spain (2003) %
Vandelli Italy (2004) %
Tahan Turkey (2005) %

11. Shared Toothbrush / Razor
Shared Needles
HCV +
HCV +
SEX
sexual transmission of HCV occurs at most with very low frequency in heterosexual couples.
Other risk factors eg. IVDU
Terrault N. Hepatology 2002;36:S99-S105

12. Early studies of HCV in MSM
1990’s - HCV prevalence: up to 23%1-3
MSM no IVDU: 1-7% 4,5
MSM IVDU: % 5,6
MSM HIV-: % 7,8
MSM HIV+: 3-39% 7,8
While sexual transmission may occur, IVDU is the major transmission route for HCV in MSM, while HIV may play a role in enhancing transmission
1. Marcellin P et al. Liver 1993;13: ; 2. Estban JI et al. Lancet 1989;2: ; 3. Tedder RS et al. BMJ 1991;302: ; 4. Bodsworth NJ et al Genitourin Med 1996;72: ; 5. Corona R et al Epidemiol Infect 1991;107: ; 7. Ndimbie OK et al. Genitourin Med 1996;72: ; 8. Ricchi E et al. Eur J Epideomiol 1992;8:

13. Sexual transmission cause of recent AHC epidemic?
HCV RNA in semen
2X more frequently in HIV+ MSM1
Concomitant STIs
Increased ‘unsafe’ sex since late 1990’s2,3
UPAI / STS / Serosorting
Precedent set: epidemic LGV4
1. Briat et al. AIDS 2005;19: Elford L et al. AIDS 2002;16: Parsons JT et al. AIDS Educ Prev 2006;18: Ward H et al. STI 2009;85:

14. Evidence for Sexual transmission
All HIV+ patients with AHC
n = 111
Mean age 36yrs, all MSM
84% G1
65% on ART
mean CD4 552
Phylogenetic analysis
Case-control study
60 cases: 130 matched controls
Questionnaire (drug & sex behaviour 12 mnths pre AHC)

15. 7 genetically distinct clusters (largest n = 43)
76% sequences included in a cluster
64% line divergences since 1995 G3 7
G1a 1 2
G1b 3 6 4 5

16. Case-control study results
Drugs
Sex
82% cases no IVDU
Increased:
none IVDU drug use
shared implements
sex under influence (91.7% vs 61.5%; P<0.001)
Multivariate analysis
After adjusting for group sex – no longer significant
Increased:
sexual partners (30 vs 10)
internet to meet partners (7X)
UPAI / fisting & sex toys / group sex
Multivariate analysis:
Group sex: R/I UPAI & fisting
Participation in 2: OR 9
Participation in ≥ 3: OR 23
Danta M et al. AIDS 2007;21:

17. Transmission network
n= 200
Ref sequences = 850
England (107) / Netherlands (58) / Germany (25) / France (12) / Australia (24) 11 monophyletic clusters:
1 – 37: UK, NL
2 – 34: UK, NL, GE, FR
3 – 19: UK, NL, GE
4 – 17: UK, GE
5 – 12: UK, NL, GE, AU
6 – 12: UK
7 – 6: NL, GE
8 – 6: UK, FR
9 – 5: AU
10 – 4: AU
11 – 4: UK

18. Transmission network
n= 200
Ref sequences = 850
England (107) / Netherlands (58) / Germany (25) / France (12) / Australia (24) 11 monophyletic clusters:
1 – 37: UK, NL
2 – 34: UK, NL, GE, FR
3 – 19: UK, NL, GE
4 – 17: UK, GE
5 – 12: UK, NL, GE, AU
6 – 12: UK
7 – 6: NL, GE
8 – 6: UK, FR
9 – 5: AU
10 – 4: AU
11 – 4: UK

19. Transmission network
n= 200
Ref sequences = 850
England (107) / Netherlands (58) / Germany (25) / France (12) / Australia (24) 11 monophyletic clusters:
1 – 37: UK, NL
2 – 34: UK, NL, GE, FR
3 – 19: UK, NL, GE
4 – 17: UK, GE
5 – 12: UK, NL, GE, AU
6 – 12: UK
7 – 6: NL, GE
8 – 6: UK, FR
9 – 5: AU
10 – 4: AU
11 – 4: UK
74% of individuals from Europe were infected with a HCV strain circulating in > 1 country

20. Transmission network
n= 200
Ref sequences = 850
England (107) / Netherlands (58) / Germany (25) / France (12) / Australia (24) 11 monophyletic clusters:
1 – 37: UK, NL
2 – 34: UK, NL, GE, FR
3 – 19: UK, NL, GE
4 – 17: UK, GE
5 – 12: UK, NL, GE, AU
6 – 12: UK
7 – 6: NL, GE
8 – 6: UK, FR
9 – 5: AU
10 – 4: AU
11 – 4: UK

21. Transmission network
n= 200
Ref sequences = 850
England (107) / Netherlands (58) / Germany (25) / France (12) / Australia (24) 11 monophyletic clusters:
1 – 37: UK, NL
2 – 34: UK, NL, GE, FR
3 – 19: UK, NL, GE
4 – 17: UK, GE
5 – 12: UK, NL, GE, AU
6 – 12: UK
7 – 6: NL, GE
8 – 6: UK, FR
9 – 5: AU
10 – 4: AU
11 – 4: UK
Isolated epidemic: 33% G3a, 50% IDU

22. Transmission network
n= 200
Ref sequences = 850
England (107) / Netherlands (58) / Germany (25) / France (12) / Australia (24) 11 monophyletic clusters:
85% of linage splits occurred since 1996, with 63% occurring after 2000

23. n= 112: June ’04 – Feb ’10 4 clusters & 3 pairs (23)
1 HIV+: 2 IVDU (all MSM)
0 HIV+: 2 IVDU ( )
n= 112: June ’04 – Feb ’10
77 HIV- (94% IVDU)
35 HIV+ (50% IVDU)
73% IVDU
18% STI
4 clusters & 3 pairs (23)
51% HIV+
8% HIV-
2 HIV+:
1 STI
2 IVDU (all MSM)
All 2 HIV+:
2 STI
0 IVDU
All 4 HIV+:
2 STI
2 IVDU
All 2 HIV+:
1 STI
1 IVDU
All individuals included in clusters or homologous pairs were MSM (except one pair of female IVDUs)
All 7 HIV+:
1 STI
6 IVDU

24. What about USA? Few reports: 2006 Peters et al 1
9 cases AHC HIV+
6 MSM / 6 RF STI
3 recent STIs
2008 Fierer et al 2
11 cases ACH in HIV+
All MSM / 10 RF STI
1 IDU
Male participants of ACTG – Longitudinal Linked Randomised Trials cohort:
Baseline prevalence 10%
n = 1830 (>7000 pt yrs follow-up)
36 seroconverted
Incidence: 0.51 / 100 pt yrs
25% IDU / 75% no IDU
SCs vs baseline HCV+: more likey
white vs black ethnicity
no hist IDU
Attended college
1. Luetkemeyer A et al. JAIDS 2006;41:31-36, 2. Fierer DS et al. JID 2008;198:

25. USA Data: CROI 2011 New York Cohort: n = 77 40 yrs all MSM CD4 477
ART 74%
IDU 20%
G1a
Boston n=9
New York n=77
San Francisco n=12
Philadelphia n= 2
Los Angeles n=1
San Diego n=1
Fierer DS et al. CROI 2011 Session 34-Oral Abstracts

26. Molecular Epidemiology of New HCV:
U.S.
Cluster 1, NY (n=10)
Cluster 4, NY (n=6)
Cluster 5, NY (n=5)
Cluster 8, NY (n=4)
Cluster 6, NY (n=5)
Cluster 7, NY (n=4)
Cluster 9, NY (n=3) 98 71
100 77 88 97 99 96 93 95 92 89 78 80
Pair A, SF
Cluster 2, NY/Bo (n=7)
Pair B, NY
Pair E, NY
Pair F, NY
Pair H, NY
Pair C, NY/SD
East coast
Cluster 3, SF/NY (n=6)
New York: 7 clusters / 4 pairs
Pair D, NY/Bo
Philadelphia
Boston: 1 pair
Mixed: 1 cluster / 1 pair
West coast
San Francisco: 1 pair
San Diego (SD)
Los Angeles 1a
Mixed Coast
Mixed coasts 1 cluster / 1 pair 1b
Pair G, Bo
0.02
Fierer DS et al. CROI 2011 Session 34-Oral Abstracts

27. Molecular Epidemiology of New HCV: International
European cluster 1 (n=38)
Australian cluster 1 (n=6)
European cluster 3 (n=18)
European cluster 2 (n=19)
European cluster 5 (n=6)
Australian cluster 2 (n=4)
European cluster 4 (n=12)
European cluster 6 (n=4) 85 95 88 94 99 95 96 87 71
U.S. cluster 5 (n=5)
U.S. cluster 1 (n=10)
U.S. cluster 2 (n=6)
U.S. cluster 9 (n=3)
U.S. cluster 6 (n=5)
U.S. cluster 7 (n=4)
U.S. cluster 4 (n=6)
U.S. cluster 9 (n=4)
U.S. cluster 3 (n=6)
Clusters (n>2)
European 94
Australian 94
U.S. 99
Europe (Eng, Neth, Ger, Fr) N=112
Australia (Syd, Melb, Brisb) N=16 77
U.S. (NY, Phil, Bo, SF, LA, SD) N=102 91
European + U.S. cluster 1a
European + Australian cluster 1b
100
0.05
Fierer DS et al. CROI 2011 Session 34-Oral Abstracts 92

28. AHC in HIV-ve MSM No regular screening, no routine LFTs
Canada (Omega Cohort Study) 20011
n = 1085, 2653 py follow-up
HIV-ve: 1 SC in IVDU / 0.038/100py
Brighton ‘00 – ’062
n = 948 / 3335 py follow-up
HIV-ve: 0.15/100 py
A number of the HIV-ve MSM later seroconverted
Australia ‘01 –’07 (Health in Men Cohort Study) 3
n= 1383, 4412 py follow-up
HIV-ve: 0.11/100 py
1. Alary M et al. Am J Pub Health 2005;95: , 2. Richardson D et al. JID 2008;197: , 3.Jin F et al. Sex Transm Infect 2010;86:25-28.

30. Is screening cost effective? analysis of strategies
Mathematical model:
HIV+ MSM, prevalence 9.8%, incidence 0.087/100 pt yrs
Timing:
none
once
5 yrly
1 yrly
6 mnthly
3 mnthly
Tool:
LFT alone
LFT & HCV Ab
LFT & HCV RNA

31. Biological vs Behavioural/Environmental
Conclusion
Biological vs Behavioural/Environmental
HIV
Drug type (‘club drugs’)
Internet
HCV transmission in HIV-positive MSM
Sexual Behaviour
Drug Behaviour
High-risk sexual practices
Shared implements (intranasal)
STIs

32. Thank you