acute hcv in hiv-infected men the ‘new’ std
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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. 10. 8. 6. Incidence of acute HCV i nfection/1000 pt yrs. 4. 2. 0. 1997. 1998. 1999. 2000. - PowerPoint PPT PresentationTRANSCRIPT
Acute HCV in HIV-infected MenThe ‘new’ STD
Dr Emma PageClinical Research FellowImperial College London
Chelsea and Westminster Hospital
Increase in acute HCV infections amongst HIV+
• Test for trend p-value using Poisson regression p<0.001• Error bars = 95% CI
Inci
denc
e of
acu
te H
CV in
fecti
on/1
000
pt y
rs
0
2
4
6
8
10
12
1997 1998 1999 2000 2001 2002 2003
Browne RE, et al. 2nd IAS 2003; Abstract 972
Reports of acute hepatitis C in HIV+ MSM
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
1
2,3
4
5
6
7
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.
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: SNAHCSurveillance 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%
HCV: SNAHCSurveillance of Newly Acquired HCV
Chronic hepatitis Croutes of transmission
Sexual transmission ?
Seroprevalence studies: heterosexual couples
n Partner HCV Concordant Ab+ve Genotype
Akahane Japan (1994) 154 27% 24%
Chayama Japan (1995) 295 9% 5%Kao Taiwan (1996) 100 17% 11%Neumayr Austria (1999) 80 5% 2.5%Sun Taiwan (1999) 214 24% 3%Stroffolini Italyn (2001) 311 10% 6%Terrault USA (2003) 401 4.2% 2.7%
Incidence of HCV:sero-discordant heterosexual couples
F/U n incidence (years) (per year)
Piazza Italy (1997) n/a 499 1%
Kao Taiwan (2000) 4 112 0.23%Marincovich Spain (2003) 3 171 0%Vandelli Italy (2004) 10 776 0%Tahan Turkey (2005) 3 216 0%
Shared Toothbrush / Razor
Shared Needles
HCV + HCV +
Other risk factors eg. IVDU
SEX
Terrault N. Hepatology 2002;36:S99-S105
sexual transmission of HCV occurs at most with very low frequency in heterosexual couples.
Early studies of HCV in MSM
1990’s - HCV prevalence: up to 23%1-3
MSM no IVDU: 1-7% 4,5
MSM IVDU: 25-50% 5,6
MSM HIV-: 0-19% 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;13:319-322; 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
1. HCV RNA in semen 2X more frequently in HIV+ MSM1
2. Concomitant STIs
3. Increased ‘unsafe’ sex since late 1990’s2,3
UPAI / STS / Serosorting
4. Precedent set: epidemic LGV4
Sexual transmission cause of recent AHC epidemic?
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.
All HIV+ patients with AHC 1999-2005
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)
Evidence for Sexual transmission
G1a
G1b
G3
7 genetically distinct clusters (largest n = 43) 76% sequences included in a cluster 64% line divergences since 1995
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2
3
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Case-control study results
Sex
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
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
After adjusting for group sex – no longer significant
Danta M et al. AIDS 2007;21:983-91.
Transmission network
England (107) / Netherlands (58) / Germany (25) / France (12) / Australia (24)
11 monophyletic clusters:
n= 200Ref sequences = 850
1 – 37: UK, NL2 – 34: UK, NL, GE, FR3 – 19: UK, NL, GE4 – 17: UK, GE5 – 12: UK, NL, GE, AU6 – 12: UK
7 – 6: NL, GE8 – 6: UK, FR9 – 5: AU10 – 4: AU11 – 4: UK
Transmission network
n= 200Ref sequences = 850
1 – 37: UK, NL2 – 34: UK, NL, GE, FR3 – 19: UK, NL, GE4 – 17: UK, GE5 – 12: UK, NL, GE, AU6 – 12: UK
7 – 6: NL, GE8 – 6: UK, FR9 – 5: AU10 – 4: AU11 – 4: UK
England (107) / Netherlands (58) / Germany (25) / France (12) / Australia (24)
11 monophyletic clusters:
Transmission network
n= 200Ref sequences = 850
1 – 37: UK, NL2 – 34: UK, NL, GE, FR3 – 19: UK, NL, GE4 – 17: UK, GE5 – 12: UK, NL, GE, AU6 – 12: UK
7 – 6: NL, GE8 – 6: UK, FR9 – 5: AU10 – 4: AU11 – 4: UK
74% of individuals from Europe were infected with a HCV strain circulating in > 1 country
England (107) / Netherlands (58) / Germany (25) / France (12) / Australia (24)
11 monophyletic clusters:
Transmission network
n= 200Ref sequences = 850
1 – 37: UK, NL2 – 34: UK, NL, GE, FR3 – 19: UK, NL, GE4 – 17: UK, GE5 – 12: UK, NL, GE, AU6 – 12: UK
7 – 6: NL, GE8 – 6: UK, FR9 – 5: AU10 – 4: AU11 – 4: UK
England (107) / Netherlands (58) / Germany (25) / France (12) / Australia (24)
11 monophyletic clusters:
Transmission network
n= 200Ref sequences = 850
1 – 37: UK, NL2 – 34: UK, NL, GE, FR3 – 19: UK, NL, GE4 – 17: UK, GE5 – 12: UK, NL, GE, AU6 – 12: UK
7 – 6: NL, GE8 – 6: UK, FR9 – 5: AU10 – 4: AU11 – 4: UK
Isolated epidemic: 33% G3a, 50% IDU
England (107) / Netherlands (58) / Germany (25) / France (12) / Australia (24)
11 monophyletic clusters:
Transmission network
n= 200Ref sequences = 850
85% of linage splits occurred since 1996, with 63% occurring after 2000
England (107) / Netherlands (58) / Germany (25) / France (12) / Australia (24)
11 monophyletic clusters:
All 4 HIV+:2 STI2 IVDU
All 7 HIV+:1 STI6 IVDU
All 2 HIV+:1 STI1 IVDU
All 2 HIV+:2 STI0 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 STI2 IVDU (all MSM)
0 HIV+: 2 IVDU ( )1 HIV+: 2 IVDU (all MSM)
All individuals included in clusters or homologous pairs were MSM (except one pair of female IVDUs)
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: 1996-2008 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
San Francisco n=12
Los Angeles n=1
San Diego n=1
New York n=77
Boston n=9
Philadelphia n= 2
Fierer DS et al. CROI 2011 Session 34-Oral Abstracts
New York Cohort:n = 77•40 yrs•all MSM•CD4 477•ART 74%•IDU 20%•G1a
Cluster 3, SF/NY (n=6)
Cluster 2, NY/Bo (n=7)
Pair A, SF
0.02
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
99
96
93
95
93
92
89
98
78
80
71
Pair D, NY/Bo
Pair C, NY/SDPair B, NY
Pair E, NYPair F, NY
Pair H, NY
Pair G, Bo
1a
1b
West coastSan Francisco: 1 pair
San Diego (SD)Los Angeles
Mixed CoastMixed coasts 1 cluster / 1 pair
New York: 7 clusters / 4 pairsPhiladelphia
East coast
Boston: 1 pair
Molecular Epidemiology of New HCV: U.S.
Mixed: 1 cluster / 1 pair
Fierer DS et al. CROI 2011 Session 34-Oral Abstracts
92
100
99
77
95
88
85
94
91
94
0.05
94
94
99
95
96
87
71
871a
1b
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)
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)
Molecular Epidemiology of New HCV:International
Australian
European
U.S.
Europe (Eng, Neth, Ger, Fr) N=112
U.S. (NY, Phil, Bo, SF, LA, SD) N=102Australia (Syd, Melb, Brisb) N=16
Clusters (n>2)
European + Australian cluster
European + U.S. cluster
Fierer DS et al. CROI 2011 Session 34-Oral Abstracts
AHC in HIV-ve MSM
No regular screening, no routine LFTs
1. Canada (Omega Cohort Study) 20011
n = 1085, 2653 py follow-up HIV-ve: 1 SC in IVDU / 0.038/100py
2. Brighton ‘00 – ’062
n = 948 / 3335 py follow-up HIV-ve: 0.15/100 py A number of the HIV-ve MSM later seroconverted
3. 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
Timing:1. none2. once3. 5 yrly4. 1 yrly5. 6 mnthly6. 3 mnthly
Tool:1. LFT alone 2. LFT & HCV Ab3. LFT & HCV RNA
Conclusion
Sexual Behaviour
Drug Behaviour
HCV transmission in HIV-positive MSM
High-risk sexual practices
Internet Drug type (‘club drugs’)
STIs
Shared implements (intranasal)
Biological vs Behavioural/Environmental
HIV
Thank you