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

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

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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

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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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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




7 – 6: NL, GE8 – 6: UK, FR9 – 5: AU10 – 4: AU11 – 4: 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






7 – 6: NL, GE8 – 6: UK, FR9 – 5: AU10 – 4: AU11 – 4: UK






7 – 6: NL, GE8 – 6: UK, FR9 – 5: AU10 – 4: AU11 – 4: UK

Isolated epidemic: 33% G3a, 50% IDU





85% of linage splits occurred since 1996, with 63% occurring after 2000



All 4 HIV+:2 STI2 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)

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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


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U.S. cluster 5 (n=5)



U.S. cluster 9 (n=3)U.S. cluster 6 (n=5)U.S. cluster 7 (n=4)




European cluster 1 (n=38)

Australian cluster 1 (n=6)




Australian cluster 2 (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


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

Documents

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