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 100K), but stable in HIV/AIDS surveillance in Europe EU (5.7 per 100K). ECDC 2010 report • Predominant mode of transmission is MSM. What is the structure of • Predominant mode the transmission varies by area. networks?

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 HIV/AIDS surveillance in Europe EU (5.7 per 100K). ECDC 2010 report • Predominant mode of transmission is MSM. What is the structure of • Predominant mode the transmission varies by area. networks?

Phylodynamics Limitations Fundamental insight • Influenced by Viral evolution and sampling epidemic spread occur on • Cannot determine the same timescale direction of transmission Routine clinical • Sequences not taken diagnostics allow us to at time of track the epidemic seroconversion

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

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)

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)

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).

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

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)

Petridish plot

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%

The large networks

A closer look

Large cluster growth Linear growth implies rate of transmission is slowing Consistent with ECDC 2010 report, Prosperi et al.

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

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

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)

Country-level assortitivity Assortitivity coefficient err − er 2 � AC = � � r 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

MSM petridish plot Little cross-border transmission • Italy, Germany– many small clusters • Sweden– One large cluster, several small

MSM phylogenetic tree What can we say about branch length? Clustering? Supports findings from distance-based methods Phylogenetic tree of MSM cluster

Hetero petridish plot Little cross-border transmission • Portugal – localized • Italy/Sweden – threshold issue? • Sweden/Other – mixing

IVDU petridish plot Little cross-border transmission • Portugal – two clusters • Italy/Sweden – One large, several medium clusters

THANKS RESINA Study Group EuResist Project