Acute HCV in HIV-infected Men
The ‘new’ STD
Dr Emma Page
Clinical Research Fellow
Imperial College London
Chelsea and Westminster Hospital
Increase in acute HCV infections
amongst HIV+
12
Incidence of acute HCV
infection/1000 pt yrs
10
8
6
4
2
0
1997
1998
1999
2000
• Test for trend p-value using Poisson regression p<0.001
• Error bars = 95% CI
Browne RE, et al. 2nd IAS 2003; Abstract 972
2001
2002
2003
Reports of acute hepatitis C in HIV+
MSM
1
4
7
5
2,3
6
1. Giraudon I et al. STI 2007;84:111-116, 2. Ghosn et al. STI 2006; 82: 458-460 ; 3. Gambotti et al. Euro Surveill 2005; 10: 115-117; 4. Gotz et
al. AIDS 2005; 19: 969-974. 5. Vogel M et al. J Viral Hepat 2005; 12: 207-211; 6. Matthews GV AIDS 2007;21:2112-2113; 7 Luetkemeyer A et
al. JAIDS 2006;41:31-36
Increased AHC or increased testing?
Number longitudinal studies in HIV+ MSM:

London & Brighton1:
• 2000 < 0.1/100 py; 2002 0.7/100 py; 2006 0.12/100 py
• Clinics with greatest annual increase had routine screening
throughout study period

UK – PHI2
• 1999-2006: n=155; 3mnthly HCV Ab
• 0% 1999 to 2002 / 2.5% 2004 / 3.9% 2006

ACS3
• 1984-2003; n=514
• 1984-1999 0.08/100 py vs 2000-2003 0.87/100 py
1. Giraudon I et al. STI 2007;84:111-116, 2. Fox J et al. AIDS 2008;22:666-667, 3.van de Laar T et al. JID 2007;196:230-238.
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
HCV: SNAHC
Surveillance of Newly Acquired HCV

Risk factors:

Drug taking:
• IDU
• Non-IDU

16% (7% last 6 mnths)
60% (C 39%, K 27%, Cystal 20%, E 18%)
Sexual
•
•
•
•
STI
UPAI
Fisting
Sex & drugs
63% (31% early STS, 22% chlamydia)
83% (75% UPIAI, 73% UPRAI)
22% (69% UPIF, 65% UPRF)
90%
Chronic hepatitis C
routes of transmission
Sexual transmission ?
Seroprevalence studies:
heterosexual couples
n
Akahane
Chayama
Kao
Neumayr
Sun
Stroffolini
Terrault
Japan (1994)
Japan (1995)
Taiwan (1996)
Austria (1999)
Taiwan (1999)
Italyn (2001)
USA (2003)
154
295
100
80
214
311
401
Partner HCV
Ab+ve
Concordant
Genotype
27%
9%
17%
5%
24%
10%
4.2%
24%
5%
11%
2.5%
3%
6%
2.7%
Incidence of HCV:
sero-discordant heterosexual couples
F/U
(years)
n
incidence
(per year)
Piazza
Italy (1997)
n/a
499
1%
Kao
Marincovich
Vandelli
Tahan
Taiwan (2000)
Spain (2003)
Italy (2004)
Turkey (2005)
4
3
10
3
112
171
776
216
0.23%
0%
0%
0%
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
Early studies of HCV in MSM

1990’s - HCV prevalence: up to 23%1-3
MSM no IVDU:
 MSM IVDU:
 MSM HIV-:
 MSM HIV+:

1-7% 4,5
25-50% 5,6
0-19% 7,8
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;13:319-322; 2. Estban JI et al. Lancet 1989;2:294-297; 3. Tedder RS et al. BMJ 1991;302:1299-1302; 4.
Bodsworth NJ et al Genitourin Med 1996;72:118-122; 5. Corona R et al Epidemiol Infect 1991;107:667-672; 7. Ndimbie OK et al. Genitourin
Med 1996;72:213-216; 8. Ricchi E et al. Eur J Epideomiol 1992;8:804-807
Sexual transmission cause of recent
AHC epidemic?
1.
HCV RNA in semen

2X more frequently in HIV+ MSM1
2.
Concomitant STIs
3.
Increased ‘unsafe’ sex since late
1990’s2,3

4.
UPAI / STS / Serosorting
Precedent set: epidemic LGV4
1. Briat et al. AIDS 2005;19:1827-1835. 2 Elford L et al. AIDS 2002;16:1537-1544. 3 Parsons JT et al. AIDS Educ Prev 2006;18:139-149. 4 Ward H
et al. STI 2009;85:173-175.
Evidence for Sexual transmission


All HIV+ patients with AHC 19992005
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)



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
Case-control study results
Drugs


82% cases no IVDU
Increased:





none IVDU drug use
shared implements
sex under influence (91.7% vs
61.5%; P<0.001)
Multivariate analysis

Sex
After adjusting for group sex
– no longer significant
Danta M et al. AIDS 2007;21:983-91.
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
Transmission
network
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
n= 200
Ref sequences = 850
Transmission
network
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
n= 200
Ref sequences = 850
Transmission
network
England (107) / Netherlands (58) / Germany (25) /
France (12) / Australia (24)
11 monophyletic clusters:
1 – 37: UK, NL
7 – 6: NL, GE
2 – 34: UK, NL, GE, FR
8 – 6: UK, FR
3 – 19: UK, NL, GE
9 – 5: AU
4 – 17: UK, GE
10 – 4: AU
5 – 12: UK, NL, GE, AU
11 – 4: UK
6 – 12: UK
74% of individuals from Europe were infected
with a HCV strain circulating in > 1 country
n= 200
Ref sequences = 850
Transmission
network
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
n= 200
Ref sequences = 850
Transmission
network
England (107) / Netherlands (58) / Germany (25) /
France (12) / Australia (24)
11 monophyletic clusters:
1 – 37: UK, NL
7 – 6: NL, GE
2 – 34: UK, NL, GE, FR
8 – 6: UK, FR
3 – 19: UK, NL, GE
9 – 5: AU
4 – 17: UK, GE
10 – 4: AU
5 – 12: UK, NL, GE, AU
11 – 4: UK
6 – 12: UK
Isolated epidemic: 33% G3a, 50% IDU
n= 200
Ref sequences = 850
Transmission
network
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
n= 200
Ref sequences = 850
1 HIV+: 2 IVDU (all MSM)
n= 112: June ’04 – Feb ’10




77 HIV- (94% IVDU)
35 HIV+ (50% IVDU)
73% IVDU
18% STI
All 2 HIV+:
2 STI
0 IVDU

51% HIV+
8% HIVAll individuals included in
clusters or homologous
pairs were MSM (except
one pair of female IVDUs)
2 HIV+:
1 STI
2 IVDU (all MSM)
All 4 HIV+:
2 STI
2 IVDU
4 clusters & 3 pairs (23)

0 HIV+: 2 IVDU ( )
All 2 HIV+:
1 STI
1 IVDU
All 7 HIV+:
1 STI
6 IVDU
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: 19962008


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;198:683-686
USA Data: CROI 2011
Boston n=9
New York n=77
San Francisco n=12
Los Angeles n=1
San Diego n=1
Fierer DS et al. CROI 2011 Session 34-Oral Abstracts
Philadelphia n= 2
New York Cohort:
n = 77
• 40 yrs
• all MSM
• CD4 477
• ART 74%
• IDU 20%
• G1a
Cluster 1, NY (n=10)
Molecular
Epidemiology of
New HCV:
U.S.
East coast
New York:
Philadelphia
Boston:
77
99
Pair A, SF
Cluster 2, NY/Bo
(n=7)
88
80
Pair B, NY
Pair C, NY/SD
97
Cluster 3, SF/NY
(n=6)
93
7 clusters / 4 pairs
93
Pair D, NY/Bo
Cluster 5, NY (n=5)
99
1 pair
Cluster 6, NY (n=5)
92
71
Mixed:
Cluster 9, NY (n=3)
1 cluster / 1 pair
96
West coast
San Francisco:
Cluster 7, NY (n=4)
Pair E, NY
Pair F, NY
98
1 pair
95
Cluster 8, NY (n=4)
78
San Diego (SD)
Los Angeles
1a
Mixed Coast
Mixed coasts
1b
Cluster 4, NY (n=6)
89
1 cluster / 1 pair
98
100
0.02
71
Fierer DS et al. CROI 2011 Session 34-Oral Abstracts
Pair G, Bo
Pair H, NY
Molecular
Epidemiology of
New HCV:
International
European cluster 1 (n=38)
85
95
Australian cluster 1 (n=6)
88
European cluster 3 (n=18)
94
U.S. cluster 1 (n=10)
U.S. cluster 2 (n=6)
95
Clusters (n>2)
European
94
European cluster 2 (n=19)
Australian
94
U.S.
European cluster 5 (n=6)
U.S. cluster 5 (n=5)
94
Australian cluster 2 (n=4)
99
U.S. cluster 9 (n=3)
U.S. cluster 6 (n=5)
U.S. cluster 7 (n=4)
71
Europe (Eng, Neth, Ger, Fr) N=112
Australia (Syd, Melb, Brisb) N=16
U.S. (NY, Phil, Bo, SF, LA, SD) N=102
96
77
U.S. cluster 4 (n=6)
99
91
European + U.S. cluster
1a
European + Australian cluster
1b
Fierer DS et al. CROI 2011 Session 34-Oral Abstracts
European cluster 4 (n=12)
U.S. cluster 9 (n=4)
87
U.S. cluster 3 (n=6)
87
100
0.0
5
92
European cluster 6 (n=4)
AHC in HIV-ve MSM
No regular screening, no routine LFTs
1.
Canada (Omega Cohort Study) 20011


2.
Brighton ‘00 – ’062



3.
n = 1085, 2653 py follow-up
HIV-ve: 1 SC in IVDU / 0.038/100py
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;95:502-505, 2. Richardson D et al. JID 2008;197:1213-1214, 3.Jin F et al. Sex Transm
Infect 2010;86:25-28.
Is screening cost effective?
analysis of strategies
Mathematical model:
HIV+ MSM, prevalence 9.8%, incidence 0.087/100 pt yrs
1.
2.
3.
4.
5.
6.
Timing:
none
once
5 yrly
1 yrly
6 mnthly
3 mnthly
1.
2.
3.
Tool:
LFT alone
LFT & HCV Ab
LFT & HCV RNA
Conclusion
Biological vs
Behavioural/Environmental
HIV
Internet
Drug type (‘club
drugs’)
HCV transmission in HIVpositive MSM
Drug
Behaviour
Sexual
Behaviour
High-risk sexual
practices
STIs
Shared implements
(intranasal)
Thank you