Rapid communications. undertook an epidemiological investigation to identify the likely source of this increase.

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1 Rapid commuicatios Ijectio of ew psychoactive substace sow blow associated with recetly acquired HIV ifectios amog homeless people who iject drugs i Dubli, Irelad, 2015 C Giese 1 2, D Igoe 2, Z Gibbos 3, C Hurley 4, S Stokes 3, S McNamara 3, O Eis 4, K O Doell 2, E Keea 3, C De Gascu 5 6, F Lyos 7, M Ward 4, K Dais 1 8, R Gly 4, A Waters 5, M Fitzgerald 4, o behalf of the outbreak cotrol team 9 1. Europea Programme for Itervetio Epidemiology Traiig (EPIET), Europea Cetre for Disease Prevetio ad Cotrol, (ECDC), Stockholm, Swede 2. HSE Health Protectio Surveillace Cetre, Dubli, Irelad 3. HSE Natioal Drug Treatmet Cetre, Dubli, Irelad 4. Departmet of Public Health, Dubli, Irelad 5. Natioal Virus Referece Laboratory, Uiversity College Dubli, Dubli, Irelad 6. School of Medicie, Uiversity College Dubli, Dubli, Irelad 7. St. James s Hospital, Dubli, Irelad 8. Frech Istitute for Public Health Surveillace (Istitut de Veille Saitaire, IVS), Paris, Frace 9. The members of the team are listed at the ed of the article Correspodece: Coralie Giese (coraliegiese@hotmail.com) Citatio style for this article: Giese C, Igoe D, Gibbos Z, Hurley C, Stokes S, McNamara S, Eis O, O Doell K, Keea E, De Gascu C, Lyos F, Ward M, Dais K, Gly R, Waters A, Fitzgerald M. Ijectio of ew psychoactive substace sow blow associated with recetly acquired HIV ifectios amog homeless people who iject drugs i Dubli, Irelad, Euro Surveill. 2015;20(40):pii= DOI: Article submitted o 01 October 2015 / accepted o 08 October 2015 / published o 08 October 2015 I February 2015, a outbreak of recetly acquired HIV ifectios amog people who iject drugs (PWID) was idetified i Dubli, followig similar outbreaks i Greece ad Romaia i We compared drug ad risk behaviours amog 15 HIV cases ad 39 cotrols. Ijectig a sythetic cathioe, sow blow, was associated with recet HIV ifectio (AOR: 49; p = 0.003). Prevetio ad cotrol efforts are uderway amog PWID i Dubli, but may also be eeded elsewhere i Europe. Backgroud I February 2015, the Departmet of Public Health (DPH), Health Service Executive (HSE) i Dubli, Irelad, idetified a uexpected icrease i cases of acute HIV ifectio amog people who iject drugs (PWID); three cases were diagosed p24 atige-positive i Jauary ad February 2015, compared with two cases diagosed durig the whole year i 2014 [1]. Drug treatmet cliicias had also idetified icreased use of a ew psychoactive substace (NPS) alphapyrrolidiovaleropheoe (α-pvp), kow as sow blow, which was beig used by chaotic PWID, ad which they suspected might be liked to the icrease [2]. Cliicias defied the chaotic group as homeless PWID who, if o opioid substitutio treatmet (OST), required daily attedace at their treatmet programme, due to cotiued use of a variety of other illicit substaces i a itesive or chaotic way. We udertook a epidemiological ivestigatio to idetify the likely source of this icrease. Epidemiological ivestigatio ad case defiitio Cliicias i Dubli provided iformatio o mode of trasmissio for ew HIV diagoses, ad otified ew HIV diagoses i PWID immediately to the DPH. Cliicias asked all cases about the use of sow blow ad at-risk sexual practices ad whether they were homeless. Cases were crosschecked with data from the Dubli Regio Homeless Executive s accommodatio cliet database for periods of accommodatio betwee 1 October 2013 ad 30 Jue We defied a case as HIV diagosis i PWID i Dubli reportig first HIV-positive test sice Jauary 2014: a cofirmed case had recet HIV ifectio (oe or more of: p24 atige-positive, history of egative HIV test withi 12 moths of first positive test, acute serocoversio illess, or rececy assay test); a probable case had a HIV diagosis of ukow duratio but with a epidemiological lik (sexual itercourse or drug sharig) to a cofirmed case. We excluded cases with o evidece of recet ifectio or epidemiological liks to recet HIV diagoses, ad cases previously diagosed abroad. 1

2 Figure 1 Number of recet HIV ifectios or diagoses with epidemiological lik to recet ifectios i PWID i Dubli, by moth of first diagosis, Jauary 2014 to September 2015 a ( = 38) 7 6 probable (=6) cofirmed (=32) Number of cases Ja Feb Mar Apr May Ju Jul Aug Sep Oct Nov Dec Ja Feb Mar Apr May Ju Jul Aug Sep a Data as at 30 September Moth of diagosis Table 1 Distributio of demographic ad social characteristics betwee cases (=15) ad cotrols (=39), case cotrol study, outbreak of recet HIV ifectio i PWID, Dubli, Irelad, 2015 Demographic ad social characteristics Case Cotrol P value Sex Female Home/relatives 7 14 Place of residece a Homeless/hostels Priso Media (rage) Media (rage) P value Age (years) 35 (25 51) 33 (19 51) 0.87 Age at first ijectio (years) 17 (11 39) 20 (11 44) 0.14 Duratio of ijectio (years) 16 (3 26) 11 (0 39) 0.14 PWID: people who iject drugs. a I the previous 12 moths. Case cotrol study We coducted a case cotrol study amog chaotic PWID, ijectig withi the previous 12 moths, residig i Dubli ad diagosed sice July We icluded cofirmed ad probable cases. A list of HIV test-egative (withi three moths) PWID attedig the Natioal Drug Treatmet Cetre (NDTC) i Dubli, registered by NDTC as homeless ad requirig daily attedace due to chaotic behaviour, was geerated. A radom sample was take from this list, usig radom figures geerated from Excel. Patiets o this list who atteded ad agreed to participate, were icluded. We coducted face-to-face or telephoe iterviews, to collect iformatio o drug use icludig frequecy of use, sexual ad ijectig at-risk practices, ad livig coditios. Participats were asked to report exposures for 12 moths before HIV positive diagosis (cases) or egative diagosis (cotrols). To examie associatios betwee exposures ad ifectio, we calculated adjusted odds ratios (OR) ad 95% cofidece itervals (CI) usig multiple logistic regressio. Iclusio criteria used were p<0.2 for model etry. Laboratory ivestigatios HIV serological diagosis was based o the Abbott Architect HIV Ag/Ab Combo, Biomerieux VIDAS HIV Duo Ultra ad P24II, ad Fujirebio INNO-LIA HIV I/II SCORE assays; rececy testig was performed o the Sedia Bioscieces HIV-1 LAg-Avidity EIA; ad HIV-1 RNA testig was performed o the Abbott Molecular m

3 Table 2 Factors positively associated with recet HIV ifectio i PWID i uivariate aalysis, case cotrol study, outbreak of recet HIV ifectio i PWID, Dubli, Irelad, 2015 Factors positively associated with recet HIV ifectio Cases Cotrols Crude OR (N = 15) (N = 39) (95% CI) P value Drugs Admiistratio Methamphetamie a Ijectig ( ) < Sow blow a Ijectig ( ) < Ijectig daily 8 1 b 128 (10 1,595) < Sow blow (frequecy) a Ijectig occasioally 5 6 b 13 (2.1 85) Amphetamies c Usig ( ) 0.03 Other head shop drugs c Usig ( ) 0.03 Bezodiazepies c Usig ( ) 0.05 Crack c Ijectig ( ) 0.39 Other ( ) 0.3 Heroi c Ijectig ( ) 0.12 Ijectig ( ) 0.21 Cocaie c Other ( ) 0.81 Ijectig 0 2 NC NC NC Opiates c Other ( ) 0.86 Sexual practices Sex with PWID d ( ) Had sex d ( ) 0.7 Sex while high d,e ( ) 0.68 Uprotected sex e ( ) 0.54 At-risk ijectig practices Use of used eedles or syriges ( ) < Use of used filters ( ) Use of used cotaiers or spoos for mixig d ( ) Media (rage) Media (rage) Number of differet drugs used 5 (1-9) 3 (1-7) 1.7 f ( ) Number of people with whom shared or reused works 1 (0-15) 0 (0-10) 1.2 f ( ) 0.09 CI: cofidece iterval; NC: Not calculable; OR: odds ratio. a Referece: ot ijectig i the previous 12 moths or other route of admiistratio. b Five missig values. c Referece: ot usig i the previous 12 moths. d Oe missig value. e Amog those who had sex. f Per additioal uit icrease. RealTime system. HIV subtypig has bee described elsewhere [3]. Urie samples of cases attedig NDTC were screeed by the NDTC laboratory usig a i-house Liquid Chromatography/Mass Spectrometry (LC/MS) NPS screeig method. Sice 2008, the laboratory of the NDTC has regularly redeveloped its methods i order to meet the challege of testig for NPS by addig ew drugs as they appear i Europe [4,5]. For the purposes of the study, the laboratory of the NDTC developed a tailored NPS LC/MS screeig method targetig 26 NPS drugs ad commo amphetamies i urie. The method covered all relevat drugs detected i the laboratory i recet years icludig α-pvp which was first added to the NPS scree i Results Epidemiological ivestigatio ad case cotrol study I 2014 ad 2015, 38 cofirmed ad probable cases of HIV subtype B were reported (32 cofirmed ad six probable) (Figure). Amog these, 16 were female; media age was 35 years (rage: 24 51). Sice Jauary 2014, 29 of the 38 had bee registered with homeless accommodatio services, seve were ot registered, ad iformatio was ot available for two. All females ad 13 of the 20 males with iformatio available, 3

4 Table 3 Factors positively associated with recet HIV ifectio i multiple regressio aalysis, case cotrol study, outbreak of recet HIV ifectio i PWID, Dubli, Irelad, 2015 Factors positively associated with recet HIV ifectio Adjusted odds ratio 95% cofidece itervals P value Ijectig sow blow Reusig eedles /syriges Havig sex with PWID Female sex were homeless. I all 18 of the 20 PWID with iformatio available, reported ijectig sow blow. At-risk practices, amely sex with PWID, or sex with a HIVpositive parter were reported by 20 of the 38 cases. Thirtee cases reported both usig sow blow ad sexual at-risk practices. Oe death was reported. We recruited 15 cases (12 cofirmed, three probable) of 24 cases ad 39 cotrols. Cases were iterviewed betwee 25 May ad 18 August 2015 at ifectious disease cliics (=5), drug cliics (=7), i priso (=2) or by telephoe (=1). Cotrols were iterviewed at NDTC. All participats but oe were erolled i methadoe maiteace treatmet. Cases did ot differ from cotrols i terms of age, age at first ijectio, duratio of ijectio or livig circumstaces (Table 1). Females were more likely to become ifected tha males. Compared with cotrols, cases were more likely to have reported ijectig methamphetamie, sow blow, cosumig amphetamies, other head shop drugs ( legal highs ) or bezodiazepies (through various routes of admiistratio) (Table 2). All cases who reported ijectig methamphetamie also reported ijectig sow blow. Compared with those who did ot iject i the previous 12 moths, the odds of recet HIV ifectio was higher amog PWIDs who reported occasioal use (weekly, mothly or less tha a moth) ad highest i those who reported ijectig sow blow daily (Table 2). Compared with cotrols, cases were more likely to have reused eedles or syriges, to have used several types of drugs i the previous 12 moths ad to have had sex with PWID parters. I the multivariable model, ijectig sow blow, usig used eedles/syriges, ad havig sex with PWID were the oly exposures which remaied idepedetly associated with HIV (Table 3). Drug aalysis Urie samples from 12 cases i the case cotrol study were tested for NPS. Five were positive: α-pvp ( = 4), α-pvp ad MDPBP ( = 1); seve were egative. Discussio This ivestigatio amog homeless chaotic PWID i Dubli is the first evidece of a associatio betwee ijectig sow blow ad recet HIV ifectio, with daily sow blow ijectors beig at highest risk. The epidemiological fidigs are supported by the detectio of α-pvp i the urie of cases. Sow blow has bee foud to cotai α-pvp, a secod geeratio cathioe ad is closely related to MDPV with similar abuse liability [2,4,6]. These fidigs are cosistet with the kow stimulat effects of sythetic cathioes ad at-risk ijectig practices liked to their use [6-11]. Drug treatmet cliicias raised cocers that cliets who ijected sow blow geerally exhibited more chaotic behaviours, leadig to dis-ihibitio, more sharig of eedles ad syriges, ad uprotected sex. Betwee 2005 ad 2014, more tha 81 sythetic cathioe derivatives were reported to the Europea Uio (EU) Early Warig System [12]. Sigificat quatities of NPS are seized aually i Irelad [13]. I 2011, α-pvp was first detected i urie samples tested for NPS by NDTC. Uries tested for NPS i 2015 cotai predomiatly α-pvp, petedroe ad MDPBP [5]. Use of sythetic cathioes by homeless chaotic PWID populatios has previously bee reported i Irelad ad i Europe [6,14]. I Dubli, there are more tha 500 homeless PWID, a sigificat populatio at risk of HIV ifectio [15]. At the time of the study, 252 of ca 520 attedees at the NDTC (48.5%) were homeless. The geeral situatio regardig homelessess i Dubli has also deteriorated sigificatly over 2014 ad 2015, with a 28% icrease i the umber of idividuals accessig emergecy accommodatio i Dubli i the 12 moths to Jue 2015 [16]. The NDTC has a remit for providig OST for homeless PWID, but respodig adequately to the eeds of these PWID remais challegig. I Dubli, measures take iclude multi-discipliary work to egage HIV-positive PWID i HIV care ad, where appropriate, o atiretroviral therapy: offerig HIV testig to PWID; awareess raisig amog cliets, cliicias ad etworks of PWID about ijectig head shop drugs such as sow blow, sexual at-risk behaviours ad of the eed to egage with methadoe ad treatmet services. Services have bee ehaced i terms of cotact tracig ad active case fidig 4

5 ad provisio of greater access to eedle exchage services by stregtheig eedle/syrige provisio through outreach. There were limitatios i udertakig this ivestigatio. Cases ad cotrols were difficult to recruit amog homeless chaotic PWID, exposed to illegal ad at-risk behaviours. I the descriptive epidemiology, homeless status was determied by askig the patiets if they were homeless, ad by crosscheckig with the homeless service database. If however homeless persos did t register for ay homeless service they might ot have bee idetified as homeless. For the aalytical study, cotrols idetified by NDTC as homeless ad chaotic were icluded i the study. However, we foud that the homeless status of some participats had chaged with a miority o loger reportig homelessess, although all remaied chaotic. Cases were more likely to have bee i priso. However this was subject to selectio bias as we did ot select cotrols i prisos but icluded cases who were i priso. Behavioural fidigs were based o self-reported iformatio ad some participats were uder the effect of drugs while iterviewed. This may have had altered the accuracy of measuremet of past exposures. Irelad is the third coutry reportig a outbreak of HIV amog PWID withi the past five years i Europe, after Greece ad Romaia i 2011 [14,17]. A similar icrease has also recetly bee reported i Glasgow ad Clyde i Jue 2015 [18]. Outbreaks of HIV amog PWID have also bee reported i Israel i 2012 ad i Idiaa, Uited States, i early 2015 [19,20]. With low coverage of harm reductio activities such as eedle ad syrige programmes ad OST i most Europea coutries, ad a growth of the market i ew psychoactive substaces, i particular the detectio of α -PVP i the 28 EU Member States, the risk of HIV amog PWID, ad particularly homeless chaotic PWID is likely to be icreasig i Europe [2,12,21]. It may be of beefit for other coutries to cosider stregtheig prevetio programmes for PWID [21-23]. Outbreak Cotrol team members Departmet of Public Health Dubli: Orla Eis, Margaret Fitzgerald, Carolie Hurley, Roa Gly, Mary Ward Natioal Drug Treatmet Services: Zoria Gibbos, Eamo Keea, Shay Keatig, Seamus Nooe Addictio Services: Des Crowley, Deirdre Dowdall, Joh Crave Safety Net Homeless Service: Austi O Carroll HSE Social Iclusio: Joe Doyle, Joe Barry Natioal Virus Referece Laboratory: Jeff Coell, Susie Coughla, Cillia de Gascu GUIDE St James s Hospital: Fioa Lyos, Siead Murphy, Georgia Nagle Mater Misericordiae Uiversity Hospital: Paddy Mallo, Deirdre Morley, Gerard Sheeha Health Protectio Surveillace Cetre: Coralie Giese, Derval Igoe, Kate O Doell Europea Programme for Itervetio Epidemiology Traiig (EPIET), Europea Cetre for Disease Prevetio ad Cotrol, (ECDC), Stockholm, Swede: Coralie Giese Ackowledgemets The authors wish to thak all those who participated to the study, all iterviewers from NDTC, GUIDE cliic, St James s hospital, Curlew road cliic, Dochas cetre, the Mater hospital, Thompso Cetre, Ms Áie Shie from NDTC Laboratory for testig ad aalysis of urie samples, Berie O Dooghue Hyes Head of Research ad Pathie Maphosa Research Assistat from the Dubli Regio Homeless Executive. Authors would also like to thak Patricia Garvey EPIET fellow at HPSC for her advice durig the aalysis, Public Health Eglad for sharig their examples of questioaire related to drug cosumptio, ad for their Virus Referece Departmet s (Colidale) assistace with HIV rececy testig, ad Alicia Barrasa Blaco, EPIET coordiator, for her advice i desigig the questioaire. Coflict of iterest Noe declared. Authors cotributios Desig of the study: GC, ID, GZ, KE FM, WM, O DK Iterviews of participats: GZ, GR, LF Data aalysis: GC, ID, DK Writig of article: GC, ID, DK Data collectio ad aalysis of cases i outbreak: GC, HC, EO, O DK Laboratory diagosis: DGC, WA Drug testig: SS, McNS Article review: GC, ID, GZ, KE, DK, O DK, SS, McNS, LF, WM, GR, FM, DGC, WA, EO, HC Refereces 1. Gly R, Giese C, Eis O, Gibbos Z, O Doell K, Hurley C, et al. Icrease i diagoses of recetly acquired HIV i people who iject drugs. Epi-Isight 2015 Jul;16(7). Available from: &t= Europea Moitorig Cetre for Drugs ad Drug Addictio (EMCDDA). EMCDDA Europol Joit Report o a ew psychoactive substace: 1-pheyl-2-(1-pyrrolidiyl)-1- petaoe (α-pvp). Lisbo: EMCDDA. Sep Available from: alpha-pvp 3. De GascuCF, WatersA, RegaCM, O HalloraJ, FarrellG, CoughlaS, et al. Huma immuodeficiecy virus type 1 i Irelad: phylogeetic evidece for risk group-specific subepidemics. AIDS Res Hum Retroviruses. 2012;28(9): DOI: /AID PMID: O ByrePM, KavaaghPV, McNamaraSM, StokesSM. Screeig of stimulats icludig desiger drugs i urie usig a liquid chromatography tadem mass spectrometry system.j Aal 5

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