Phylogenetic Cluster Analysis Identifies Virological and Behavioral Drivers of Human Immunodeficiency Virus Transmission in Men Who Have Sex With Men
Nadine Bachmann, Katharina Kusejko, Huyen Nguyen, Sandra E Chaudron, Claus Kadelka, Teja Turk, Jürg Böni, Matthieu Perreau, Thomas Klimkait, Sabine Yerly, Manuel Battegay, Andri Rauch, Alban Ramette, Pietro Vernazza, Enos Bernasconi, Matthias Cavassini, Huldrych F. Günthard, Roger D. Kouyos, Swiss HIV Cohort Study, A Anagnostopoulos, Manuel Battegay, Enos Bernasconi, Jürg Böni, Dominique L. Braun, H C Bucher, Alexandra Calmy, Matthias Cavassini, Angela Ciuffi, G Dollenmaier, Matthias Egger, Luigia Elzi, Jan Fehr, Jacques Fellay, Hansjakob Furrer, Christoph A. Fux, Huldrych F. Günthard, David Haerry, Barbara Hasse, Hans H. Hirsch, Matthew Hoffmann, Irène Hösli, M Huber, Christian R. Kahlert, Laurent Kaiser, Olivia Keiser, Thomas Klimkait, Roger D. Kouyos, Helen Kovari, Bruno Ledergerber, G Martinetti, Begoña Martínez de Tejada, Catia Marzolini, Karin J. Metzner, N Müller, Dunja Nicca, P Paioni, Giuseppe Pantaleo, Matthieu Perreau, Andri Rauch, Christoph Rudin, Alexandra Scherrer, Patrick Schmid, René Speck, M Stöckle, Philip Tarr, Alexandra Trkola, Pietro Vernazza, Gilles Wandeler, Richard D Weber, Sabine Yerly
Abstract
BACKGROUND: Identifying local outbreaks and their drivers is a key step toward curbing human immunodeficiency virus (HIV) transmission and potentially achieving HIV elimination. Such outbreaks can be identified as transmission clusters extracted from phylogenetic trees constructed of densely sampled viral sequences. In this study, we combined phylogenetic transmission clusters with extensive data on virological suppression and behavioral risk of cluster members to quantify the drivers of ongoing transmission over 10 years. METHODS: Using the comprehensive Swiss HIV Cohort Study and its drug-resistance database, we reconstructed phylogenetic trees for each year between 2007 and 2017. We identified HIV transmission clusters dominated by men who have sex with men (MSM) and determined their annual growth. We used Poisson regression to assess if cluster growth was associated with a per-cluster infectivity and behavioral risk score. RESULTS: Both infectivity and behavioral risk scores were significantly higher in growing MSM transmission clusters compared to nongrowing clusters (P ≤ .01). The fraction of transmission clusters without infectious members acquiring new infections increased significantly over the study period. The infectivity score was significantly associated with per-capita incidence of MSM transmission clusters in 8 years, while the behavioral risk score was significantly associated with per-capita incidence of MSM transmission clusters in 3 years. CONCLUSIONS: We present a phylogenetic method to identify hotspots of ongoing transmission among MSM. Our results demonstrate the effectiveness of treatment as prevention at the population level. However, the significantly increasing number of new infections among transmission clusters without infectious members highlights a relative shift from diagnosed to undiagnosed individuals as drivers of HIV transmission in Swiss MSM.