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Virus Evol. 2018 Sep 18;4(2):vey024. doi: 10.1093/ve/vey024. eCollection 2018 Jul.

Inferring the age difference in HIV transmission pairs by applying phylogenetic methods on the HIV transmission network of the Swiss HIV Cohort Study.

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Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zürich, Rämistrasse 100, Zürich, Switzerland.
Institute of Medical Virology, University of Zürich, Winterthurerstrasse 190, Zürich, Switzerland.
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Petersgraben 4, CH-4031 Basel; University of Basel, Petersplatz 1, Basel, Switzerland.
Division of Infectious Diseases, Regional Hospital Lugano, Via Tesserete 46, Lugano, Switzerland.
Laboratory of Virology and Division of Infectious Diseases, Genève University Hospital, Rue Gabrielle-Perret-Gentil 4, CH-1205 Genève; University of Genève, 24 rue du Général-Dufour, Genève, Switzerland.
Division of Infectious Diseases, Lausanne University Hospital, Rue du Bugnon 46, Lausanne, Switzerland.
Division of Infectious Diseases, Cantonal Hospital St Gallen, Rorschacher Strasse 95, St. Gallen, Switzerland.
Molecular Virology, Department of Biomedicine, University of Basel, Petersplatz 10, Basel, Switzerland.
Clinic for Infectious Diseases, Bern University Hospital, Freiburgstrasse 18, Bern; University of Bern, Hochschulstrasse 6, CH-3012 Bern, Switzerland.


Age-mixing patterns are of key importance for understanding the dynamics of human immunodeficiency virus (HIV)-epidemics and target public health interventions. We use the densely sampled Swiss HIV Cohort Study (SHCS) resistance database to study the age difference at infection in HIV transmission pairs using phylogenetic methods. In addition, we investigate whether the mean age difference of pairs in the phylogenetic tree is influenced by sampling as well as by additional distance thresholds for including pairs. HIV-1 pol-sequences of 11,922 SHCS patients and approximately 240,000 Los Alamos background sequences were used to build a phylogenetic tree. Using this tree, 100 per cent down to 1 per cent of the tips were sampled repeatedly to generate pruned trees (N = 500 for each sample proportion), of which pairs of SHCS patients were extracted. The mean of the absolute age differences of the pairs, measured as the absolute difference of the birth years, was analyzed with respect to this sample proportion and a distance criterion for inclusion of the pairs. In addition, the transmission groups men having sex with men (MSM), intravenous drug users (IDU), and heterosexuals (HET) were analyzed separately. Considering the tree with all 11,922 SHCS patients, 2,991 pairs could be extracted, with 954 (31.9 per cent) MSM-pairs, 635 (21.2 per cent) HET-pairs, 414 (13.8 per cent) IDU-pairs, and 352 (11.8 per cent) HET/IDU-pairs. For all transmission groups, the age difference at infection was significantly (P < 0.001) smaller for pairs in the tree compared with randomly assigned pairs, meaning that patients of similar age are more likely to be pairs. The mean age difference in the phylogenetic analysis, using a fixed distance of 0.05, was 9.2, 9.0, 7.3 and 5.6 years for MSM-, HET-, HET/IDU-, and IDU-pairs, respectively. Decreasing the cophenetic distance threshold from 0.05 to 0.01 significantly decreased the mean age difference. Similarly, repeated sampling of 100 per cent down to 1 per cent of the tips revealed an increased age difference at lower sample proportions. HIV-transmission is age-assortative, but the age difference of transmission pairs detected by phylogenetic analyses depends on both sampling proportion and distance criterion. The mean age difference decreases when using more conservative distance thresholds, implying an underestimation of age-assortativity when using liberal distance criteria. Similarly, overestimation of the mean age difference occurs for pairs from sparsely sampled trees, as it is often the case in sub-Saharan Africa.


HIV; age structure; cophenetic distance; phylogenies; sampling

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