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

doi:10.1093/cid/ciaa411

Phylogenetic Cluster Analysis Identifies Virological and Behavioral Drivers of Human Immunodeficiency Virus Transmission in Men Who Have Sex With Men

Clin Infect Dis. 2021 Jun 15;72(12):2175-2183. doi: 10.1093/cid/ciaa411.

Authors

Nadine Bachmann^{1

2}, Katharina Kusejko^{1

2}, Huyen Nguyen^{1

2}, Sandra E Chaudron^{1

2}, Claus Kadelka^{1

2}, Teja Turk^{1

2}, Jürg Böni², Matthieu Perreau³, Thomas Klimkait⁴, Sabine Yerly⁵, Manuel Battegay⁶, Andri Rauch⁷, Alban Ramette⁷, Pietro Vernazza⁸, Enos Bernasconi⁹, Matthias Cavassini¹⁰, Huldrych F Günthard^{1

2}, Roger D Kouyos^{1

2}; Swiss HIV Cohort Study

Collaborators

Swiss HIV Cohort Study:
A Anagnostopoulos, M Battegay, E Bernasconi, J Böni, D L Braun, H C Bucher, A Calmy, M Cavassini, A Ciuffi, G Dollenmaier, M Egger, L Elzi, J Fehr, J Fellay, H Furrer, C A Fux, H F Günthard, D Haerry, B Hasse, H H Hirsch, M Hoffmann, I Hösli, M Huber, C R Kahlert, L Kaiser, O Keiser, T Klimkait, R D Kouyos, H Kovari, B Ledergerber, G Martinetti, B Martinez de Tejada, C Marzolini, K J Metzner, N Müller, D Nicca, P Paioni, G Pantaleo, M Perreau, A Rauch, C Rudin, A U Scherrer, P Schmid, R Speck, M Stöckle, P Tarr, A Trkola, P Vernazza, G Wandeler, R Weber, S Yerly

Affiliations

¹ Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
² University of Zurich, Institute of Medical Virology, Zurich, Switzerland.
³ Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
⁴ Molecular Virology, Department Biomedicine-Petersplatz, University of Basel, Basel, Switzerland.
⁵ Laboratory of Virology, Geneva University Hospital, Geneva, Switzerland.
⁶ Department of Infectious Diseases and Hospital Epidemiology, University Hospital Basel and University of Basel, Basel, Switzerland.
⁷ Institute for Infectious Diseases, Bern University Hospital and University of Bern, Bern, Switzerland.
⁸ Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital of St Gallen, St Gallen, Switzerland.
⁹ Division of Infectious Diseases, Regional Hospital Lugano, Lugano, Switzerland.
¹⁰ Division of Infectious Diseases, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.

PMID: 32300807
DOI: 10.1093/cid/ciaa411

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.

Keywords: HIV transmission clusters; MSM; drivers of transmission; phylogenetics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cluster Analysis
Cohort Studies
HIV Infections* / epidemiology
HIV-1*
Homosexuality, Male
Humans
Male
Phylogeny
Sexual and Gender Minorities*