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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.

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Presentation on theme: "Acute HCV in HIV-infected Men The new STD Dr Emma Page Clinical Research Fellow Imperial College London Chelsea and Westminster Hospital."— Presentation transcript:

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+ Test for trend p-value using Poisson regression p<0.001 Error bars = 95% CI Incidence of acute HCV i nfection/1000 pt yrs 0 2 4 6 8 10 12 1997199819992000200120022003 Browne RE, et al. 2nd IAS 2003; Abstract 972

3 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

4 Increased AHC or increased testing? Number longitudinal studies in HIV+ MSM: London & Brighton 1 : 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 – PHI 2 1999-2006: n=155; 3mnthly HCV Ab 0% 1999 to 2002 / 2.5% 2004 / 3.9% 2006 ACS 3 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.

5 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

6 Risk factors: Drug taking: IDU16% (7% last 6 mnths) Non-IDU60% (C 39%, K 27%, Cystal 20%, E 18%) Sexual STI63% (31% early STS, 22% chlamydia) UPAI83% (75% UPIAI, 73% UPRAI) Fisting22% (69% UPIF, 65% UPRF) Sex & drugs 90% HCV: SNAHC Surveillance of Newly Acquired HCV

7 Chronic hepatitis C routes of transmission

8 Sexual transmission ?

9 Seroprevalence studies: heterosexual couples n Partner HCV Concordant Ab+ve Genotype AkahaneJapan (1994)15427%24% ChayamaJapan (1995)295 9% 5% KaoTaiwan (1996)10017%11% NeumayrAustria(1999) 80 5%2.5% SunTaiwan (1999)21424%3% StroffoliniItalyn (2001)31110%6% TerraultUSA (2003)4014.2%2.7%

10 Incidence of HCV: sero-discordant heterosexual couples F/U nincidence (years)(per year) PiazzaItaly (1997)n/a4991% KaoTaiwan (2000)41120.23% MarincovichSpain (2003)31710% VandelliItaly (2004)107760% TahanTurkey (2005)32160%

11 Shared Toothbrush / Razor Shared Needles 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.

12 Early studies of HCV in MSM 1990s - 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

13 1. HCV RNA in semen 2X more frequently in HIV+ MSM 1 2. Concomitant STIs 3. Increased unsafe sex since late 1990s 2,3 UPAI / STS / Serosorting 4. Precedent set: epidemic LGV 4 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.

14 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

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

16 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.

17 Transmission network England (107) / Netherlands (58) / Germany (25) / France (12) / Australia (24) 11 monophyletic clusters: n= 200 Ref sequences = 850 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 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 England (107) / Netherlands (58) / Germany (25) / France (12) / Australia (24) 11 monophyletic clusters:

19 Transmission network n= 200 Ref sequences = 850 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 England (107) / Netherlands (58) / Germany (25) / France (12) / Australia (24) 11 monophyletic clusters:

20 Transmission network n= 200 Ref sequences = 850 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 England (107) / Netherlands (58) / Germany (25) / France (12) / Australia (24) 11 monophyletic clusters:

21 Transmission network n= 200 Ref sequences = 850 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 England (107) / Netherlands (58) / Germany (25) / France (12) / Australia (24) 11 monophyletic clusters:

22 Transmission network n= 200 Ref 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:

23 All 4 HIV+: 2 STI 2 IVDU All 7 HIV+: 1 STI 6 IVDU All 2 HIV+: 1 STI 1 IVDU All 2 HIV+: 2 STI 0 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) 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 )

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: 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

25 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

26 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 96 93 95 93 92 89 98 78 80 71 Pair D, NY/Bo Pair C, NY/SD Pair B, NY Pair E, NY Pair F, NY Pair H, NY Pair G, Bo 1a 1b West coast San Francisco: 1 pair San Diego (SD) Los Angeles Mixed Coast Mixed coasts1 cluster / 1 pair New York: 7 clusters / 4 pairs Philadelphia 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

27 92 100 99 77 95 88 85 94 91 94 0.0 5 94 99 95 96 87 71 87 1a 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=102 Australia (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

28 AHC in HIV-ve MSM No regular screening, no routine LFTs 1. Canada (Omega Cohort Study) 2001 1 n = 1085, 2653 py follow-up HIV-ve: 1 SC in IVDU / 0.038/100py 2. Brighton 00 – 06 2 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.

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30 Is screening cost effective? analysis of strategies Mathematical model: HIV+ MSM, prevalence 9.8%, incidence 0.087/100 pt yrs Timing: 1. none 2. once 3. 5 yrly 4. 1 yrly 5. 6 mnthly 6. 3 mnthly Tool: 1. LFT alone 2. LFT & HCV Ab 3. LFT & HCV RNA

31 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

32 Thank you


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