Molecular Surveillance of Recent HIV-Infections in Germany - PowerPoint PPT Presentation

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

3 Representativity HIV-Meldungen (n=19.078) InzSurvHIV (n=11.232) HI V-Reports I nzSurv (2011-2014/ I) Unbekannt Report Status Unknown Melde- status Doppelmeldung Multiple Reports Erstdiagnose First Diagnosis unbekannt Unknown Transmission Transmission andere Others Hetero Hetero IVDA IVDU MSM MSM >45 >45 30-45 Alter 30-45 Age 18-29 18-29 <18 <18 fehlende Angaben No Data Sex Sex männlich Male weiblich Female 2014 2014 Year 2013 2013 Jahr 2012 2012 2011 2011 0% 10% 20% 30% 40% 50% 60% 70% 80% 90%

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

5 W orkflow in the Lab Sam ple receipt Recency Test ( BED-I gG Capture EI A) ~30% recently acquired ( ≤140 days) <> long standing (>140 days)

6 I solation of vRNA from Recent HI V I nfections + ~60 % of all new HIV Diagnoses Report DPS (IfSG §7(3)) recent infections Network of 81 diagnostic labs Recency Test

7 W orkflow in the Lab Sam ple receipt ( DPS) Recency Test ( BED-I gG Capture EI A) RNA isolation from vRNA DPS of recent infections Viral load and RT-PCR ( V L > 1 0 0 0 copies/ m l) Population sequencing + HI V-genotyping A) HI V-resistance m utations B) HI V-1 subtype -> link to notification data

8 Transm itted Drug Resistance in Recently Aquired HI V I nfections ( n= 9 9 4 ) TDR 2012 - 2014 (n=994) sensitive NRTI 5.3 % NNRTI resistent sensitiv 12.6 % 2.9 % 87.4 % PI dual 3.2 % multi Median prevalence of TDR: 12.57 %; (124/994)[95 % CI 10.51; 14.81] Slow decreasing trend observed in the 'German HIV-1 Seroconverter Cohort' (EHR Poster 2012 ; 1996-2010; RKI-Workshop 2014 und IWHOD 2015; 1996-2013)

9 Trends of Transm itted Drug Resistance 40 Proportion of transmitted drug resistance (%) 35 P Trend = 0.09 30 25 20 17,9 15,1 14,1 15 12,0 11,7 9,2 10 5 0 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

1 0 - sie in einer Region infiziert wurden, in der resistente Viren gehäuft übertragen werden (> 10 %)

1 1 Trends in NRTI s, NNRTI s, and PI s 16 14 NNRTI Proportion of resistant viruses (%) NRTI 12 p Trend > 0.05 PI 10 8 6 4 2 0 2012/I 2012/II 2013/I 2013/II 2014/I 2014/II Half-year of Diagnosis N (994) = 5 64 172 163 239 300

1 2 Proportion of TDR According to Transm ission Group 2012-2014 (n= 994) 30 p >0.05 25 Proportion of TDR (%) 20 84/609 15 113/891 11/98 30/274 8/83 10 2/28 5 0/5 0 MSM Hetero IVDU no data Male men Female women no data Transmission group Gender

1 3 Prevalence of HI V-1 Subtypes 2012-2014 (n= 994)  A (East Europe + Asia)  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' Update bitte Median prevalence of non-B subtypes: 22.54 %; (224/994) [95 % CI 20.56; 25.77]

1 4 Trend of Non-B Subtypes in Recently Acquired HI V I nfections 40 p Trend = 0.04 35 Proportion of non-B subtypes (%) 30 27,2 24,3 25 22,7 19,8 20 14,1 15 10,7 10 5 0 2012/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

1 5 Trend for Selected Subtypes Proportion of non-B subtypes ( % )

1 6 Proportion of Non-B Subtypes According to Transm ission Group 2012-2014 (n= 994) p< 0.0001 100 p <0.0001 Proportion of HIV-1 non-B subtypes (%) 90 p< 0.001 4/5 p <0.0001 80 71/98 70 60 14/28 50 66/83 40 78/274 30 20 149/891 66/609 10 0 MSM Hetero IVDU no data Male men women Female no data Transmission group Gender

1 7 Trend of Non-B Subtypes in MSM 20 Proportion of non-B subtypes (%) p Trend < 0.02 15 13 10 10 5 3 0 2012 2013 2014 Year of Diagnosis

1 8 TDR frequency in Subtype B and Non-B I nfections 100% 90% 80% 70% Proportion (%) resistent 60% sensitive 50% 40% 30% 20% 10% 0% Subtyp B Subtype B non-B Subtypen Non-B Subtype Odds ratio 0.47 [95% CI: 0.27-0.82]

1 9 Sum m ary  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 2012-2014 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 2012-2014 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.

2 0 Outlook  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%

2 1 Acknow ledgm ents • Alexandra Hofmann • Barbara G.-Bartmeyer • Viviane Bremer Andrea Claudia Karolin Hauser Meixenberger Kücherer • Osamah Hamouda MASTER HIV/HEP-Partners Diagnostic Laboratories of the Network

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