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Acute HCV in HIV-infected Men The ‘new’ STD

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.

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Acute HCV in HIV-infected Men The ‘new’ STD

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  1. Acute HCV in HIV-infected MenThe ‘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 6 Incidence of acute HCV infection/1000 pt yrs 4 2 0 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+ MSM 4 1 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

  4. 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.

  5. HCV: SNAHCSurveillance 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: 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%

  7. Chronic hepatitis Croutes of transmission

  8. Sexual transmission ?

  9. 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%

  10. Incidence of HCV:sero-discordant heterosexual couples F/Un 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%

  11. Shared Needles Shared Toothbrush / Razor 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: 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. 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;19:1827-1835. 2 Elford L et al. AIDS 2002;16:1537-1544. 3 Parsons JT et al. AIDS EducPrev 2006;18:139-149. 4 Ward H et al. STI 2009;85:173-175.

  14. Evidence for Sexual transmission • 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)

  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 Sex 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 • 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;21:983-91.

  17. 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

  18. 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

  19. 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 74% of individuals from Europe were infected with a HCV strain circulating in > 1 country

  20. 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

  21. 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 Isolated epidemic: 33% G3a, 50% IDU

  22. 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

  23. 1 HIV+: 2 IVDU (all MSM) 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- 0 HIV+: 2 IVDU ( ) 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: 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 • 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. San Diego (SD) Los Angeles Mixed coasts 1 cluster / 1 pair Boston: 1 pair San Francisco: 1 pair Philadelphia New York: 7 clusters / 4 pairs 77 0.02 Cluster 1, NY (n=10) Pair B, NY 99 88 80 97 93 Pair E, NY 93 Pair F, NY 99 Cluster 5, NY (n=5) 92 Cluster 6, NY (n=5) 71 Cluster 9, NY (n=3) 96 Cluster 7, NY (n=4) 98 95 Pair H, NY 78 Cluster 8, NY (n=4) 89 Cluster 4, NY (n=6) 98 100 71 Molecular Epidemiology of New HCV: U.S. Pair A, SF Cluster 2, NY/Bo (n=7) Pair C, NY/SD Cluster 3, SF/NY (n=6) East coast Pair D, NY/Bo Mixed: 1 cluster / 1 pair West coast 1a Mixed Coast Pair G, Bo 1b Fierer DS et al. CROI 2011 Session 34-Oral Abstracts

  27. Australia (Syd, Melb, Brisb) N=16 U.S. (NY, Phil, Bo, SF, LA, SD) N=102 Europe (Eng, Neth, Ger, Fr) N=112 94 U.S. European Australian 0.05 European + Australian cluster European + U.S. cluster U.S. cluster 1 (n=10) European cluster 1 (n=38) U.S. cluster 2 (n=6) 95 Australian cluster 1 (n=6) European cluster 3 (n=18) U.S. cluster 5 (n=5) 94 U.S. cluster 9 (n=3) 71 European cluster 2 (n=19) U.S. cluster 6 (n=5) 96 U.S. cluster 7 (n=4) U.S. cluster 4 (n=6) European cluster 5 (n=6) 99 Australian cluster 2 (n=4) U.S. cluster 9 (n=4) 87 87 U.S. cluster 3 (n=6) European cluster 4 (n=12) European cluster 6 (n=4) Molecular Epidemiology of New HCV:International 85 95 88 Clusters (n>2) 94 94 99 77 91 1a 1b 100 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;95:502-505, 2. Richardson D et al. JID 2008;197:1213-1214, 3.Jin F et al. Sex Transm Infect 2010;86:25-28.

  29. 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

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

  31. Thank you

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