A phylodynamic analysis of HIV-1 in Germany

A phylodynamic analysis of HIV-1 in Germany Prabhav Kalaghatgi Max Planck Institute for Informatics, Saarbrücken RKI workshop 2015, Berlin

Number of cases 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 10000 9000 8000 7000 6000 5000 4000 3000 2000 1000 0 2006 2007 2008 2009 2010 2011 2012 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 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. ECDC. Annual epidemiological report 2014. Prabhav Kalaghatgi 2/14

Motivation HIV incidence is not reducing and the epidemic needs to be monitored. Prabhav Kalaghatgi 3/14

Motivation HIV incidence is not reducing and the epidemic needs to be monitored. Viruses sampled from patients sharing a transmission event are closely related. Prabhav Kalaghatgi 3/14

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. Prabhav Kalaghatgi 3/14

Patient data 2349 patients from Seroconverter cohort (SC) 5283 patients from RESINA cohort 2000 Patients Cohort RESINA SC 1000 0 HET IVDA MSM Other/Unknown factor(infectionroute) Prabhav Kalaghatgi 4/14

Sequence data 753 nt of pol gene sites under selection removed (WHO list) predominantly subtype B (COMET) 300 200 Patients Cohort RESINA SC 100 0 1995 2000 2005 2010 2015 Sampling date Prabhav Kalaghatgi 5/14

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 50 86 83 64 76 56 92 75 I K 45 56 73 29 100 43 91 J L N 11 89 25 28 29 42 52 F O M E 75 D P C Q R G S T B H A U 91 Z W 0.18 0.16 0.14 0.12 0.10 0.08 0.06 0.04 0.02 X V Y 0 Prosperi et al. Nat. Commun.; 2011 Prabhav Kalaghatgi 6/14

Cluster size distribution Number of clusters 0 100 200 300 400 500 2 5 8 11 16 20 25 30 36 53 Transmission cluster size Prabhav Kalaghatgi 7/14

Proportion of RESINA and SC patients in each cluster 60 40 Cluster size count 300 200 100 20 0 0.0 0.4 0.8 Proportion of patients from RESINA Prabhav Kalaghatgi 8/14

Clustering by infection route MSM HET IVDA Other/Unknown Prabhav Kalaghatgi 9/14

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 Prabhav Kalaghatgi 10/14

Time-scaled tree for largest cluster (n = 53, MSM) inferred using BEAST RESINA SC 1995.0 2000.0 2005.0 2010.0 Time Prabhav Kalaghatgi 11/14

Time-scaled tree for largest cluster (n = 53, MSM) inferred using BEAST RESINA SC 1995.0 2000.0 2005.0 2010.0 Time Tree height Prabhav Kalaghatgi 11/14

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 Prabhav Kalaghatgi 12/14

Summary HIV-1 sequences from 7632 patients (SC, RESINA) were analyzed. Prabhav Kalaghatgi 13/14

Summary HIV-1 sequences from 7632 patients (SC, RESINA) were analyzed. 3327 (44%) patients were present in 956 transmission clusters. Prabhav Kalaghatgi 13/14

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. Prabhav Kalaghatgi 13/14

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. Prabhav Kalaghatgi 13/14

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. Prabhav Kalaghatgi 13/14

Acknowledgements Universitätsklinikum Köln Elena Knops Eugen Schülter Rolf Kaiser RKI Claudia Kücherer Andrea Hauser Norbert Bannert Barbara Bartmeyer MPI Informatik Prabhav Kalaghatgi Nico Pfeifer Joachim Büch Thomas Lengauer Uniklinik Düsseldorf Björn Jensen Prabhav Kalaghatgi 14/14