Phylodynamics of HIV in Germany and Europe Glenn Lawyer AREVIR - - PowerPoint PPT Presentation

phylodynamics of hiv in germany and europe
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Phylodynamics of HIV in Germany and Europe Glenn Lawyer AREVIR - - PowerPoint PPT Presentation

Phylodynamics of HIV in Germany and Europe Glenn Lawyer AREVIR 2012, Bonn, Germany 4 May 2012 Continuing HIV transmission in Europe 27,116 newly diagnosed cases in 28 EU/EEA countries 18% increase in newly diagnosed cases (7.8 per


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Phylodynamics of HIV in Germany and Europe

Glenn Lawyer

AREVIR 2012, Bonn, Germany

4 May 2012

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Continuing HIV transmission in Europe

  • 27,116 newly diagnosed

cases in 28 EU/EEA countries

  • 18% increase in newly

diagnosed cases (7.8 per 100K), but stable in EU (5.7 per 100K).

  • Predominant mode of

transmission is MSM.

  • Predominant mode

varies by area.

HIV/AIDS surveillance in Europe ECDC 2010 report

What is the structure of the transmission networks?

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Continuing HIV transmission in Europe

  • 27,116 newly diagnosed

cases in 28 EU/EEA countries

  • 18% increase in newly

diagnosed cases (7.8 per 100K), but stable in EU (5.7 per 100K).

  • Predominant mode of

transmission is MSM.

  • Predominant mode

varies by area.

HIV/AIDS surveillance in Europe ECDC 2010 report

What is the structure of the transmission networks?

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Phylodynamics

Fundamental insight

Viral evolution and epidemic spread occur on the same timescale Routine clinical diagnostics allow us to track the epidemic

Limitations

  • Influenced by

sampling

  • Cannot determine

direction of transmission

  • Sequences not taken

at time of seroconversion

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What is the pattern of new infections?

Network(s) structure

  • cluster size

distribution

  • bounded or growing?
  • loose or dense

coupling?

Crossover transmission

  • regions
  • transmission groups
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Previous Work – 1

UK: Two research groups, three studies

A dated phylogeny approach has revealed the HIV epidemic among MSM in London to have been episodic . . .

ECDC 2010 report

UK has high rate of newly reported infections (10.7 per 100K)

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Previous Work – 1

UK: Two research groups, three studies

A dated phylogeny approach has revealed the HIV epidemic among MSM in London to have been episodic . . .

ECDC 2010 report

UK has high rate of newly reported infections (10.7 per 100K)

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Previous Work – 2

ARCA Study (Italy)

11,541 subtype B patients

  • over 2/3rds of

sequences cluster

  • median cluster size 4
  • two large clusters

(> 1000 members)

Prosperi, MCF et al. A novel methodology for large-scale phylogeny partition. Nat. Commun. 2:321 doi: 10.1038/ncomms1325 (2011).

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RESINA Study Cohort

count percent MSM 1396 51% Endemic 382 14% Hetero 494 18% IVDA 184 7% Bisexual 40 1% Blood 16 – Unknown 235 9% TOTAL 2747 100% count percent B 1962 71% A 302 11% CRF 234 9% C 94 3% D 48 2% G 57 2% urf 35 1% TOTAL 2747 100%

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Determining clusters

Network construction

Pairwise base-pair difference Link similar sequences

Range of values

Network characteristics as similarity cutoff moves from 35-40 bpd (96.8% sequence similarity)

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Petridish plot

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By the numbers

Group n clustered small clusters MSM 1396 53-63% 35-27% Hetero 493 47-56% 33-31% Endemic 382 34-42% 30-34% IVDA 184 54-62% 25-17% Bisexual 40 50-62% 32-30% Unknown 252 53-60% 38-31% TOTAL 2747 49-58% 34-29%

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The large networks

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A closer look

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Large cluster growth

Linear growth implies rate

  • f transmission is slowing

Consistent with ECDC 2010 report, Prosperi et al.

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EuResist

Italy Germany Sweden Portugal Other MSM 951 1438 628 91 1625 IVDA 1830 159 178 146 934 HET 1759 418 286 137 2452 TOTAL 4540 2015 1092 374 5011

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EuResist

Italy Germany Sweden Portugal Other MSM 951 1438 628 91 1625 IVDA 1830 159 178 146 934 HET 1759 418 286 137 2452 TOTAL 4540 2015 1092 374 5011

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EuResist

Clustering in EuResist patients Italy Germany Sweden Portugal MSM 30% (951) 43% (1438) 66% (628) 30% (91) IVDA 26% (1830) 55% (159) 70% (178) 63% (146) HET 22% (1759) 21% (418) 39% (286) 46% (137)

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Country-level assortitivity

Assortitivity coefficient

AC =

r

  • err − er 2

r – data type err – fraction of edges between two members of r er 2 – fraction of all edges from type r Assortitivity coefficient at varying thresholds for the three main transmission groups

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MSM petridish plot

Little cross-border transmission

  • Italy, Germany–

many small clusters

  • Sweden– One

large cluster, several small

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MSM phylogenetic tree

Phylogenetic tree of MSM cluster

What can we say about branch length? Clustering? Supports findings from distance-based methods

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Hetero petridish plot

Little cross-border transmission

  • Portugal –

localized

  • Italy/Sweden –

threshold issue?

  • Sweden/Other

– mixing

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IVDU petridish plot

Little cross-border transmission

  • Portugal – two

clusters

  • Italy/Sweden –

One large, several medium clusters

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THANKS

RESINA Study Group EuResist Project