1. Prospective Observational European Study of the natural history and Treatment of Syphilis in HIV positive individuals – The POETS Study Rowley D 1, Fätkenheuer G 2, Swięcki P 3, Horban A 3, Zangerle R 4, Sabin C 5,O’Dea S 1, Mulcahy F 1. 1.The GUIDE Clinic, St James Hospital, Dublin 8, Ireland 2 Klinik I für Innere Medizin,Uniklinik Köln,Germany 3 The Hospital for Infectious Diseases,Warsaw, Poland 4 Department of Dermatology and Venereology, Innsbruck Medical University, Austria 5 University College London (UCL), London, United Kingdom

2. Background There are rises in syphilis in most Western and Eastern European Cities

3. Background Limited data around the use of Ceftriaxone and Doxycycline in HIV infected patients Concern around macrolide resistance

4. Background

5. Epidemiological synergy

6. Methods and Aims Primary: To better understand the natural history of syphilis and its response to treatment and to inform the establishment of consensus guidelines Secondary Aims: To assess level of macrolide resistance through A2058G, A2059G mutations Genotyping of samples to identify differing strains confering different patterns of virulence

7. Dublin 93% A2058G 1 London 66.6% rRNA mutation (A2058G + A 2059G) 2 Czech Rep 37.3% A2058G 3 Pattern of r23s RNA gene mutation across Europe 1.Sex Transm Dis. 2012 Oct;39(10):784-6. Treponema pallidum azithromycin resistance in Dublin, Ireland. Muldoon et Al. 2.Sex Transm Infect. 2011 Oct;87(6):486-8. doi: 10.1136/sextrans-2011-050082. High prevalence of macrolide resistant Treponema pallidum strains in a London centre. Tipple et Al 3.Acta Derm Venereol. 2012 Nov;92(6):669-74. doi: 10.2340/00015555-1335. Sequencing-based molecular typing of treponema pallidum strains in the Czech Republic: all identified genotypes are related to the sequence of the SS14 strain. Flasarova et al.

8. Methods and Aims Multicentre prospective study which commenced June 2012 175 patients, both HIV–ve and HIV+ve, were prospectively recruited from 3 sites including Koln; Germany, Dublin; Ireland and Warsaw; Poland. All patients who had a new diagnosis of syphilis were recruited.

9. Dublin 50 HIV –ve 35 HIV +ve West European =63 Eastern Europe=6 Africa =3 South America= 10 North America =1,Asia= 2 Koln 14 HIV +ve 3 HIV -ve Europe 15 Middle east =1 Asia =1 Warsaw 0 HIV –ve 73 HIV +ve Poland =72 Europe =1

10. Mode of meeting partner Ireland n=85 Poland n=73 Germany n=17 Internet42 (49%)0%10 (58.8) Clubs/bars48 (56.5%)64(87.7%)3 (17.7%) Sex venues (sauna, sex cinema) 22 (25.9)0%1 (5.9%) Commercial sex workers 7 (8.2%)1(1.4%)0% Alcohol use around time of sex 59 (69.4%)62 (84.9%)7 (41.2%) Party Drugs; E, Ketamine, GBH’G’ Cocaine 33 (38.8%)6 (8.2%)4(23.5%)

11. PATIENT HIV negative N=53 HIV positive N=122 P VALUE AGE (median yrs)31350.05 Homosexual36 (67.9%)96(78.7%) Bisexual8(15.1%)11(9%) Heterosexual9(17%)13(10.7%) Oral sex48(90.6%)113(92.6%)0.87 Anal insertive sex30(56.6%)95(77.9%)0.007 Anal receptive sex24(45.3%)97(79.9%)0.0001 Vaginal sex13(26%)21(17.4%)0.28 Fisting3(5.7%)3(2.5%)0.37 Past History of STIs20(37.7%)64(52.2%)0.1 Previous T.Pall infection4(7.6%)54(44.3%)0.0001

12. HIV +veIreland n = 35Poland n = 73Germany n = 14 On ART Virological suppression 21 (60%) 21 (100%) 37 (50.7%) 37 (95%) 9(64.2%) 9 (100%) Current CD4570460544 Nadir CD4 *median288308200 Has current partner34(40%)8(11%)7(41%) Partner aware of T PallNo 11(32%)No 7(88 %)No 4(57%) Partner aware of HIVYes 33 (94%) Yes 8 (100% )Yes 1(8%)

13. PATIENT HIV positive N=122 Viral Load <50 N=74 Viral load >50 N=48 P VALUE Oral sex113(92.6%)69(93%)44(91.7%)0.74 Anal insertive sex 95(77.9%)58(78.4%)37(77.1%)1.0 Anal receptive sex 97(79.9%)59(79.7%)38(79.2%)1.0 Vaginal sex21(17.4%)9(12.2%)12(25%)0.11

14. Staging of T.Pall infection: HIV negative N=53 HIV positive N=122 P VALUE Primary25(47.2%)23(18.9%)0.0002 Chancre present17(32.1)14(11.5%)0.002 Secondary7(13.2%)68(55.7%)0.0001 Rash 7(13.2%) 45(36.6%)0.003 Early latent6(11.3%)7(5.7%)0.22 Late latent9(17%) 16(13.1%) 0.66

15. PATIENT HIV positive N=122 HIV negative N=53 P VALUE Treatment: Any Penicillin: Benzathine Penicillin Procaine Penicillin Crystal Penicillin 71(58.2)47(88.7)0.0002 Doxycycline41(33.6)1(1.9)0.0001 Azithromycin2(1.6)01.0 Ceftriaxone6(4.9)00.18

16. Preliminary Conclusions 1.One public health message does not fit all 2.Treatment varies geographically. Though limited evidence to support the use of Doxycycline in treating syphilis, particularly in HIV+ pts, 35% of HIV + patients received Doxycycline Rx. 3.The 40 - 50% of uncontrolled viraemia is concerning, and when combined with high rates of non-disclosure, this has huge public health implications for ongoing HIV transmission. 4.Test and treat at every outpatient clinic!

17. What next? Health Warning !

18. Acknowledgements 1.The GUIDE Clinic, St James Hospital, Dublin 8, Ireland 2 Klinik I für Innere Medizin,Uniklinik Köln,Germany 3 The Hospital for Infectious Diseases,Warsaw, Poland 4 Department of Dermatology and Venereology, Innsbruck Medical University, Austria 5 University College London (UCL), London, United Kingdom

19. guidelines