Molecular Surveillance of Recent HIV-Infections in Germany. Priv.-Doz. Dr. Norbert Bannert "HIV und Other Retroviruses" Robert Koch-Institut, Berlin

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1 Molecular Surveillance of Recent HIV-Infections in Germany Priv.-Doz. Dr. Norbert Bannert "HIV und Other Retroviruses" Robert Koch-Institut, Berlin AREVIR-Meeting, May 9th 2015

2 Sampling of New HIV Diagnoses 2 ~60 % of all new HIV diagnoses Anonymous infection report (IfSG 7(3)) + Residual blood plasma on filter card (DPS) Network of 81 diagnostic laboratories

3 Representativity 3 Meldestatus Report Status Year Jahr Sex Age Alter Transmission Unbekannt Unknown Doppelmeldung Multiple Reports Erstdiagnose First Diagnosis unbekannt Unknown andere Others Hetero IVDA IVDU MSM >45 > <18 <18 fehlende Angaben No Data männlich Male weiblich Female HIV-Meldungen HIV-Reports (n=19.078) InzSurvHIV (n=11.232) ( /I) 0% 10% 20% 30% 40% 50% 60% 70% 80% 90%

4 Isolation of IgG from DPS 4 ~60 % of all new HIV diagnoses Report (IfSG 7(3)) + DPS Network of 81 diagnostic labs Recency Test

5 5 Workflow in the Lab Sample receipt Recency Test (BED-IgG Capture EIA) ~30% recently acquired ( 140 days) <> long standing (>140 days)

6 Isolation of vrna from Recent HIV Infections 6 ~60 % of all new HIV Diagnoses Report (IfSG 7(3)) + DPS Network of 81 diagnostic labs Recency Test recent infections

7 7 Workflow in the Lab Sample receipt (DPS) Recency Test (BED-IgG Capture EIA) RNA isolation from DPS of recent infections vrna Viral load and RT-PCR (V L >1000 copies/ml) Population sequencing + HIV-genotyping A) HIV-resistance mutations B) HIV-1 subtype -> link to notification data

8 Transmitted Drug Resistance in Recently Aquired HIV Infections (n=994) 8 TDR (n=994) sensitiv 87.4 % resistent 12.6 % 5.3 % 2.9 % 3.2 % sensitive NRTI NNRTI PI dual multi Median prevalence of TDR: %; (124/994)[95 % CI 10.51; 14.81] Slow decreasing trend observed in the 'German HIV-1 Seroconverter Cohort' (EHR Poster 2012 ; ; RKI-Workshop 2014 und IWHOD 2015; )

9 9 Trends of Transmitted Drug Resistance 40 Proportion of transmitted drug resistance (%) PTrend = ,9 14,1 15,1 11,7 12,0 9,2 2012/1 2012/2 2013/1 2013/2 2014/1 2014/II Half-year of Diagnosis N= 10/56 11/64 26/172 15/163 28/239 36/300

10 - sie in einer Region infiziert wurden, in der resistente Viren gehäuft übertragen werden (> 10 %) 10

11 11 Trends in NRTIs, NNRTIs, and PIs NNRTI Proportion of resistant viruses (%) p Trend > 0.05 NRTI PI /I 2012/II 2013/I 2013/II 2014/I 2014/II Half-year of Diagnosis N (994) =

12 Proportion of TDR According to Transmission Group (n=994) p> Proportion of TDR (%) /609 8/83 2/28 30/ /891 11/ MSM Hetero IVDU no data Male men Female women no data Transmission group Gender 0/5

13 Prevalence of HIV-1 Subtypes (n=994) A (East Europe + Asia) Update bitte Circulating Recombinant Form 01_AE Circulating Recombinant Form 02_AG CRF02_AG (West Africa) 'rare recombinants' 13 'Unique Recombinant Forms' 12 different 'Circulating Recombinant Forms' Median prevalence of non-b subtypes: %; (224/994) [95 % CI 20.56; 25.77]

14 Trend of Non-B Subtypes in Recently Acquired HIV Infections p Trend = 0.04 Proportion of non-b subtypes (%) ,7 14,1 19,8 22,7 27,2 24, /I 2012/II 2013/I 2013/II 2014/I 2014/II Half-year of Diagnosis N= 6/56 9/64 34/172 37/163 65/239 73/300

15 Trend for Selected Subtypes 15 Proportion of non-b subtypes (%)

16 Proportion of Non-B Subtypes According to Transmission Group (n=994) Proportion of HIV-1 non-b subtypes (%) p< p<0.001 p< /28 66/83 66/609 78/ /891 p< /98 4/5 0 MSM Hetero IVDU no data Male men women Female no data Transmission group Gender

17 17 Trend of Non-B Subtypes in MSM 20 Proportion of non-b subtypes (%) p Trend < Year of Diagnosis

18 TDR frequency in Subtype B and Non-B Infections 18 Proportion (%) 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Subtype B B non-b Non-B Subtypen resistent sensitive Odds ratio 0.47 [95% CI: ]

19 Summary 19 Within the framework of the project 'MASTER HIV/HEP' we have established a surveillance system for a representative analysis of TDR and transmitted subtypes of recent HIV infections in Germany. Data from based on 994 sequences indicate a current rate of TDR approaching the 10% level with a decreasing trend. TDR is slightly higher in MSM compared to heterosexuals. About 78% of all recent HIV infection in Germany in involved a subtype B virus. The rate of non-b infections in Germany is steeply increasing and has already reached 25%. In MSM, subtype B is still dominating new infections with a proportion of 90%, but the trend shows a clear increase of non-b in this transmission group. In heterosexuals, the proportion of non-b infections is 80%. This can be explained with the high rate of infections acquired abroad.

20 Outlook 20 Extension for the analysis TDR of integrase inhibitors Acquisition of sequences directly from diagnostic labs Increase in the sample number to achieve important significance levels Substitution of the Recency-Tests for a Recency-Algorithm Identification and analysis of transmission networks Switch from Sanger sequencing to NGS (detection of resistant minorities) Preliminary NGS threshold for minorities: 3%

21 Acknowledgments 21 Alexandra Hofmann Barbara G.-Bartmeyer Andrea Hauser Karolin Meixenberger Claudia Kücherer Viviane Bremer Osamah Hamouda MASTER HIV/HEP-Partners Diagnostic Laboratories of the Network

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