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 (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
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
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
Acquisition of Samples for the Molecular Surveillance of New HIV Diagnoses in Germany 05.05.18 Arevir-Meeting 6
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
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
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
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
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
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
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
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
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
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
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
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
08.02.16 EUPHEM 19
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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