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

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Sam pling of New HI V Diagnoses +

~60 %

• f all new

HIV diagnoses

Network of 81 diagnostic laboratories

Anonymous infection report (IfSG §7(3)) Residual blood plasma on filter card (DPS)

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Representativity

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 2011 2012 2013 2014 weiblich männlich fehlende Angaben <18 18-29 30-45 >45 MSM IVDA Hetero andere unbekannt Erstdiagnose Doppelmeldung Unbekannt Jahr Sex Alter Transmission Melde- status HIV-Meldungen (n=19.078) InzSurvHIV (n=11.232)

(2011-2014/ I)

HI V-Reports I nzSurv

Unknown Multiple Reports First Diagnosis Unknown Others Hetero IVDU MSM >45 30-45 18-29 <18 No Data Male Female 2014 2013 2012 2011

Report Status Transmission Age Sex Year

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I solation of I gG from DPS

+

DPS

Recency Test Network of 81 diagnostic labs

~60 %

• f all new

HIV diagnoses Report (IfSG §7(3))

5 Sam ple receipt Recency Test ( BED-I gG Capture EI A)

~30%

W orkflow in the Lab

recently acquired (≤140 days) <> long standing (>140 days)

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I solation of vRNA from Recent HI V I nfections

Recency Test

+

Report (IfSG §7(3)) DPS recent infections

Network of 81 diagnostic labs

~60 %

• f all new

HIV Diagnoses

7 Sam ple receipt ( DPS)

Recency Test ( BED-I gG Capture EI A)

RNA isolation from DPS of recent infections Viral load and RT-PCR ( VL> 1 0 0 0 copies/ m l)

W orkflow in the Lab

Population sequencing + HI V-genotyping

vRNA

A) HI V-resistance m utations B) HI V-1 subtype

• > link to notification data

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Transm itted Drug Resistance in Recently Aquired HI V I nfections ( n= 9 9 4 )

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)

sensitiv 87.4 %

5.3 % 2.9 % 3.2 %

resistent 12.6 %

TDR 2012 - 2014 (n=994)

sensitive NRTI NNRTI PI dual multi

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N= 10/56 11/64 26/172 15/163 28/239 36/300

Trends of Transm itted Drug Resistance

PTrend = 0.09

17,9 14,1 15,1 9,2 11,7 12,0

5 10 15 20 25 30 35 40

2012/1 2012/2 2013/1 2013/2 2014/1 2014/II

Proportion of transmitted drug resistance (%)

Half-year of Diagnosis

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• sie in einer Region

infiziert wurden, in der resistente Viren gehäuft übertragen werden (> 10 %)

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N (994) = 5 64 172 163 239 300

Trends in NRTI s, NNRTI s, and PI s

2 4 6 8 10 12 14 16

2012/I 2012/II 2013/I 2013/II 2014/I 2014/II Proportion of resistant viruses (%) Half-year of Diagnosis NNRTI NRTI PI

pTrend > 0.05

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Proportion of TDR According to Transm ission Group 2012-2014 (n= 994)

5 10 15 20 25 30

MSM Hetero IVDU no data men women no data Proportion of TDR (%)

8/83 84/609 30/274 2/28 11/98 113/891 0/5

Transmission group Gender

p>0.05

Male Female

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Prevalence of HI V-1 Subtypes

2012-2014 (n= 994)

Median prevalence of non-B subtypes: 22.54 %; (224/994) [95 % CI 20.56; 25.77]

Update bitte

• 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'

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Trend of Non-B Subtypes in Recently Acquired HI V I nfections

10,7 14,1 19,8 22,7 27,2 24,3

5 10 15 20 25 30 35 40 2012/I 2012/II 2013/I 2013/II 2014/I 2014/II Proportion of non-B subtypes (%)

Half-year of Diagnosis

pTrend = 0.04

N= 6/56 9/64 34/172 37/163 65/239 73/300

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Trend for Selected Subtypes

Proportion of non-B subtypes ( % )

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Proportion of Non-B Subtypes According to Transm ission Group

2012-2014 (n= 994)

10 20 30 40 50 60 70 80 90 100

MSM Hetero IVDU no data men women no data Proportion of HIV-1 non-B subtypes (%)

78/274 14/28 66/83 66/609

p<0.0001 p<0.001

149/891 71/98 4/5

p<0.0001

Transmission group Gender

p<0.0001

Male Female

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Trend of Non-B Subtypes in MSM

3 10 13

5 10 15 20 2012 2013 2014 Proportion of non-B subtypes (%) Year of Diagnosis

pTrend < 0.02

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TDR frequency in Subtype B and Non-B I nfections

Odds ratio 0.47 [95% CI: 0.27-0.82]

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%

Subtyp B non-B Subtypen

Proportion (%)

resistent sensitive

Non-B Subtype Subtype B

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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.

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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%

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Acknow ledgm ents

• Alexandra Hofmann
• Barbara G.-Bartmeyer
• Viviane Bremer
• Osamah Hamouda

Diagnostic Laboratories of the Network

Andrea Hauser Claudia Kücherer Karolin Meixenberger

MASTER HIV/HEP-Partners

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