A phylodynamic analysis of HIV-1 in Germany Prabhav Kalaghatgi Max - - PowerPoint PPT Presentation

A phylodynamic analysis of HIV-1 in Germany

Prabhav Kalaghatgi

Max Planck Institute for Informatics, Saarbr¨ ucken

RKI workshop 2015, Berlin

Incidence of HIV-1 in Western Europe

Figure 2. Number of diagnosed HIV reported infections adjusted for reporting delay, by transmission mode, origin and year, EU/ EEA, 2006–2012

Source: Country reports from Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Portugal, Romania, Slovakia, Slovenia, Sweden and United Kingdom. 1000 2000 3000 4000 5000 6000 7000 8000 9000 10000 2006 2007 2008 2009 2010 2011 2012 Number of cases Year of diagnosis Men who have sex with men Heterosexual cases, excluding cases from Sub- Saharan African countries Other/undetermined Heterosexual cases from sub- Saharan African countries Injecting drug use Mother-to-child transmission

• ECDC. Annual epidemiological report 2014.

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Motivation

HIV incidence is not reducing and the epidemic needs to be monitored.

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Motivation

HIV incidence is not reducing and the epidemic needs to be monitored. Viruses sampled from patients sharing a transmission event are closely related.

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Motivation

HIV incidence is not reducing and the epidemic needs to be monitored. Viruses sampled from patients sharing a transmission event are closely related. Viral sequence data collected from patients can help reconstruct transmission clusters.

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Patient data

2349 patients from Seroconverter cohort (SC) 5283 patients from RESINA cohort

1000 2000 HET IVDA MSM Other/Unknown

factor(InfectionRoute) Patients

Cohort RESINA SC

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Sequence data

753 nt of pol gene sites under selection removed (WHO list) predominantly subtype B (COMET)

100 200 300 1995 2000 2005 2010 2015 Sampling date Patients

Cohort

RESINA SC

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Identifying transmission clusters

Set of individuals that are part of the same transmission chain. 1000 bootstrap phylogenetic trees using FastTree Clusters identified as follows:

• 1. Partition tree into clades at

90% support

• 2. Add edges between patients

in same clade if seq. dist less than 0.03 sub/site

75 0.18 0.16 0.14 0.12 0.10 0.08 0.06 0.04 0.02 89 56 92 64 86 45 56 73 11 29 25 28 29 91 42 52 91 43 83 50 I J A B C D E F G H K L M N O P Q R S T U V W X Y Z 75 76 100

Prosperi et al. Nat. Commun.; 2011

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Cluster size distribution

100 200 300 400 500 Transmission cluster size Number of clusters 2 5 8 11 16 20 25 30 36 53 Prabhav Kalaghatgi 7/14

Proportion of RESINA and SC patients in each cluster

20 40 60 0.0 0.4 0.8 Proportion of patients from RESINA Cluster size 100 200 300

count

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Clustering by infection route

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• MSM

HET IVDA Other/Unknown

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Characteristics of the five largest clusters

Size Cohort Infection route Subtype 53 60% RESINA, 40%SC MSM B 37 86% RESINA, 13%SC MSM B 36 61% RESINA, 39%SC MSM B 30 83% RESINA, 17%SC IVDA B 27 22% RESINA, 78%SC MSM B

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Time-scaled tree for largest cluster (n = 53, MSM) inferred using BEAST

1995.0 2000.0 2005.0 2010.0

RESINA SC Time RESINA SC

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Time-scaled tree for largest cluster (n = 53, MSM) inferred using BEAST

1995.0 2000.0 2005.0 2010.0

RESINA SC Time RESINA SC

Tree height

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Tree heights of the five largest transmission clusters

Size Infection route Tree height (yr) Subtype 53 MSM 20 ± 2.42 B 37 MSM 15.2 ± 1.28 B 36 MSM 16.14 ± 2.52 B 30 IVDA 10.5 ± 2.83 B 27 MSM 15.35 ± 2.74 B

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Summary

HIV-1 sequences from 7632 patients (SC, RESINA) were analyzed.

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Summary

HIV-1 sequences from 7632 patients (SC, RESINA) were analyzed. 3327 (44%) patients were present in 956 transmission clusters.

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Summary

HIV-1 sequences from 7632 patients (SC, RESINA) were analyzed. 3327 (44%) patients were present in 956 transmission clusters. 195 clusters contained patients (1140) from both SC and RESINA.

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Summary

HIV-1 sequences from 7632 patients (SC, RESINA) were analyzed. 3327 (44%) patients were present in 956 transmission clusters. 195 clusters contained patients (1140) from both SC and RESINA. Analysis benefited from having data from both SC and RESINA.

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Summary

HIV-1 sequences from 7632 patients (SC, RESINA) were analyzed. 3327 (44%) patients were present in 956 transmission clusters. 195 clusters contained patients (1140) from both SC and RESINA. Analysis benefited from having data from both SC and RESINA. Most large clusters were established over 15 years ago.

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Acknowledgements

Universit¨ atsklinikum K¨

• ln

Elena Knops Eugen Sch¨ ulter Rolf Kaiser

RKI

Claudia K¨ ucherer Andrea Hauser Norbert Bannert Barbara Bartmeyer

MPI Informatik

Prabhav Kalaghatgi Nico Pfeifer Joachim B¨ uch Thomas Lengauer

Uniklinik D¨ usseldorf

Bj¨

• rn Jensen

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