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Molecular surveillance reveals a recent outbreak of HIV-1 subtype C infections among people who inject drugs (PWID) in Munich, Germany Norbert Bannert 05.05.2018 Arevir-Meeting 05.05.18 Arevir-Meeting 2 Spread of HIV Subtype A Variant FSU


  1. Molecular surveillance reveals a recent outbreak of HIV-1 subtype C infections among people who inject drugs (PWID) in Munich, Germany Norbert Bannert 05.05.2018 Arevir-Meeting

  2. 05.05.18 Arevir-Meeting 2

  3. Spread of HIV Subtype A Variant FSU (A FSU ) in the Countries of the Former Soviet Union HIV Outbreak  40-50% of new HIV-1 infections are in PWIDs (in 2007: 83%)  70% of the infections are caused by HIV-1 subtype A FSU Thomson et al. 2015 1999: 2002: 2017: HIV-1 A FSU 30,000 200,000 800,000 A FSU HIV-1 A FSU is introduced cases cases 1 cases in Russia arrives in into PWIDs (ca. 93%) 1 (ca. 70% of cases) 2 Odessa in Odessa 1 Bobkova et al. 2013 2 Estimate based on Beyrer et al. 2017 1980 1990 2000 2010 2020 05.05.18 Arevir-Meeting 3

  4. Scott County, Indiana, USA 2014-2015 HIV-1 Outbreak Austin, IN 5 HIV Infections in 2003-2014 in Austin IN • Sharp increase in new HIV diagnoses beginning in December 2014 in PWIDs • 05.05.18 Arevir-Meeting 4

  5. Scott County, Indiana, USA 2014-2015 HIV-1 Outbreak Gov. Mike Pence at a news conference in Indianapolis on March 26, 2015. Mr. Pence declared a public health emergency in response to the H.I.V. epidemic in Scott County and put aside his own views in order to allow a program to distribute clean needles to drug users. Credit Michael/NYtimes.com Conroy/Associated Press Peters et al. NEJM 2017 Indiana law made it illegal to possess • a syringe without a prescription Sharing of needles was common • (up to 6 partners) 142/181 cases injected Oxomorphone • 4-6 daily injections • 95% were HCV coinfected • Rights by Clay Duda 05.05.18 Arevir-Meeting 5

  6. Acquisition of Samples for the Molecular Surveillance of New HIV Diagnoses in Germany 05.05.18 Arevir-Meeting 6

  7. Increase of Reported New HIV-1 Diagnoses in PWIDs in Bavaria in 2016 Analysis of the statutory notification data from the southern German state of Bavaria shows a significant increase in new HIV-1 diagnoses in PWID in 2016. 29 DSS 12 DSS 09.04.18 Virologisches Seminar 7

  8. Subtyping Reveals a High Subtype C Prevalence in the Bavarian PWID Cases in 2015/2016 3/12 2015 2016 2013/2014 2015 14/29 (25%) (48%) 2016 Germany (2013-2016) 05.05.18 Arevir-Meeting 8

  9. Phylogeny of Subtype C Infections  HIV-1 subtyping of samples from Bavaria and phylogenetic analysis reveals that the increase is driven by a cluster of subtype C infections. Munich subtype C outbreak 0.02 Maximum Likelihood Tree of several hundred subtype C sequences. 23/24 cases were diagnosed in Munich 17 of the Bavarian PWID cases diagnosed between March 2015 and and 1/24 in Augsburg December 2016 (shown in blue) are part of a larger transmission cluster (red box). 05.05.18 Arevir-Meeting 9

  10. Location of Cases in Munich (4) (3) (1) (2) (1) (1) (9) (3) Stadelheimer Str. 12, 815 49 München Justizvollzugsanstalt München 05.05.18 Arevir-Meeting 10

  11. Diagnosis Dates of the Outbreak Cases recent long standing Number of Cases Month of Diagnosis  Four sequences are long-standing (time between infection and diagnosis longer than 5 months).  Only two new infection belonging to this cluster were reported from Bavaria (both from Munich) in the first six months of 2017 (Outbreak stabilization). 05.05.18 Arevir-Meeting 11

  12. Characteristics of the Individuals Associated with the Transmission Cluster of HIV-1 Subtype C Infections in Bavaria Case # Sex* Transmission group* Country of origin* Country of infection* anti-HCV HCV-RNA 1 Male PWID Eastern Europe Germany n.d. n.d. Gender (n=26) 2 Male PWID Germany Germany + + 3 Male PWID Western Europe Germany - - 4 Male PWID Germany Germany + - 5 Male PWID Germany Germany + - 6 Male PWID Germany Germany + + 7 Male PWID Eastern Europe Germany + + 8 Male PWID Germany Germany + + 9 Male PWID Germany Germany + + 10 Male HET Germany Germany + + Risk group (n=26) 11 Male MSM Germany Germany + + 12 Female PWID Germany Germany + + 13 Female PWID Germany Germany + + 14 Male PWID Germany Germany + + 15 Male PWID Germany Germany - n.d. 16 Female HET Germany Germany + + 17 Male PWID Germany Germany + + 18 Male PWID Germany Germany + + 19 Male HET Germany Germany + + Anti-HCV (n=23) 20 Not reported Not reported Not reported Not reported + n.d. 21 Male Not reported Germany Not reported + + 22 Male PWID Not reported Germany + + 23 Female HET Germany Germany + - 24 Male PWID Germany Germany n.d. n.d. 25 Male PWID Germany Germany n.d. n.d. 26 Female PWID Germany Germany + + *self-reporting Age: 26-51, Ø=36 n.d.: not done 05.05.18 Arevir-Meeting 12

  13. Recent Outbreaks among PWIDs Stadt/Region Jahr Infektionen Stabilisierung Droge Athen 2011-2012 256 2015 Kokain Tel Aviv 2012-2013 40 2014 Hagigat Scott County 2014-2015 181 2015 Oxymorphone Dublin 2014-2015 38 2015 Snow blow Luxemburg 2014-2015 67 ? Kokain Glasgow 2015 100 ? München 2015-2016 26 2017 ? 05.05.18 Arevir-Meeting 13

  14. New Psychoactive Substances (NPS) Hundreds of substances; Pharmacological effects unexplored • main chemical classes: Strong addiction effect • Synthetic Cannabinoids • Cheap and easy to buy (Internet) • Synthetic Cathinones Many were legal (legal highs) until 11/2016 • • Phenethylamines • Frequent intravenous injection common • Tryptamines • Piperazines • https://www.zauberpilzblog.net 05.05.18 Arevir-Meeting 14

  15. Risk Faktors for HIV Infection of PWID Consuming New Psychoactive Substances (NPS) • NPS associated increase in the frequency of intravenous injections • Common intravenous consumption of NPS in groups Is there an association of the Munich outbreak cases with injection of new psychoactive substances (NPS)? 15 Arevir-Meeting 05.05.18

  16. Evidence of an Association of the Munich Outbreak with a-PVP Institut für Rechtsmedizin Forensische Toxikologie Prof. Dr. rer. nat. Dipl.-Chem. Volker Auwärter + Christina Grumann (PhD) In 5 of 10 DSS a-PVP was identified ( a-PVP : α -Pyrrolidinopentiophenone) 05.05.18 Arevir-Meeting 16

  17. Summary and Conclusions  We have identified a recent local outbreak of HIV-1 subtype C infections among PWIDs in Munich with at least 26 cases (21 cases in 2016).  Health authorities in Bavaria were informed in June 2017.  The molecular surveillance of new HIV-diagnoses reported from Bavaria has been instantly intensified, but only two new case belonging to the outbreak cluster were identified in the first 6 month of 2017.  We have found strong evidence for an association of the Munich outbreak cases with needle sharing and frequent injection of a-PVP, a new psychoactive substance (synthetic cathinone).  The recent sub-epidemics in Europe show that HIV-surveillance of vulnerable groups, especially PWIDs, is an important public health issue. Despite current prevention measures, HIV-outbreaks can occur and need to be identified early to allow an adequate response.  The statutory reporting system in Germany (IfSG) together with the established RKI program “Molecular Surveillance of newly diagnosed HIV-infections (MolSurv_HIV)” is suited for an early detection and analysis of such regional HIV outbreaks. Arevir-Meeting 05.05.18 17

  18. Acknowledgments Kirsten Hanke Andrea Hauser Patrycja Machnowska Stefan Fiedler Karolin Meixenberger Britta Altmann Barbara Gunsenheimer-Bartmeyer Alexandra Hofmann Viviane Bremer Diagnostic labs Uli Marcus Ruth Zimmermann Volker Auwärter Oliver Ratmann Christina Grumann 05.05.18 Arevir-Meeting 18

  19. 08.02.16 EUPHEM 19

  20. How to Address HIV-Outbreaks Among At-Risk-Populations? Need for rapid detection of sub-epidemics Timely and comprehensive reporting of new diagnoses • Immediate analysis with regional resolution • Almost real-time phylogenetic analysis of new diagnoses • Main measures to put an HIV outbreak among PWIDs on hold Contact tracing networks Needle and syringe exchange programs (NSP) • (Scott County outbreak) Opioid substitution treatment programs (OST) • Frequent HIV-testing and assignment of cases to clusters • Linkage to care and treatment (e.g. HIV-treatment as prevention) • Seek-test-treat programs (including contact network analysis ) • Condom provision • Intensified community outreach counseling • Raising of general awareness for the HIV sub-epidemics • Effective collaboration across multiple sectors (community, local • HIV+ health authorities, federal health authorities, drug counselling HIV- services, HIV counselling services and others Respondent-driven sampling (Athens outbreak, ARISTOTLE) 05.05.18 Arevir-Meeting 20

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