A Systematic Molecular Epidemiology Screen Reveals Numerous Human Immunodeficiency Virus (HIV) Type 1 Superinfections in the Swiss HIV Cohort Study

Author:

Chaudron Sandra E12ORCID,Leemann Christine12,Kusejko Katharina12ORCID,Nguyen Huyen12ORCID,Tschumi Nadine13,Marzel Alex14,Huber Michael2,Böni Jürg2,Perreau Matthieu5,Klimkait Thomas6,Yerly Sabine7,Ramette Alban8ORCID,Hirsch Hans H910,Rauch Andri11,Calmy Alexandra712,Vernazza Pietro13,Bernasconi Enos14,Cavassini Matthias15ORCID,Metzner Karin J12,Kouyos Roger D12,Günthard Huldrych F12,Aebi-Popp K,Anagnostopoulos A,Battegay M,Bernasconi E,Böni J,Braun D L,Bucher H C,Calmy A,Cavassini M,Ciuffi A,Dollenmaier G,Egger M,Elzi L,Fehr J,Fellay J,Furrer H,Fux C A,Günthard H F,Haerry D,Hasse B,Hirsch H H,Hoffmann M,Hösli I,Huber M,Kahlert C R,Kaiser L,Keiser O,Klimkait T,Kouyos R D,Kovari H,Ledergerber B,Martinetti G,de Tejada B Martinez,Marzolini C,Metzner K J,Müller N,Nicca D,Paioni P,Pantaleo G,Perreau M,Rauch A,Rudin C,Kusejko K,Schmid P,Speck R,Stöckle M,Tarr P,Trkola A,Vernazza P,Wandeler G,Weber R,Yerly S,

Affiliation:

1. Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich , Zurich , Switzerland

2. Institute of Medical Virology, University of Zurich , Zurich , Switzerland

3. Swiss Tropical and Public Health Institute , Basel , Switzerland

4. Schulthess Klinik , Zurich , Switzerland

5. Service of Immunology and Allergy, Lausanne University Hospital, University of Lausanne , Lausanne , Switzerland

6. Department of Biomedicine, University of Basel , Basel , Switzerland

7. Laboratory of Virology, Geneva University Hospitals , Geneva , Switzerland

8. Institute for Infectious Diseases, University of Bern , Bern , Switzerland

9. Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel , Basel , Switzerland

10. Clinical Virology, Laboratory Medicine, University Hospital Basel , Basel , Switzerland

11. Department of Infectious Diseases, Bern University Hospital, University of Bern , Bern , Switzerland

12. Division of Infectious Diseases and Faculty of Medicine, University of Geneva , Geneva , Switzerland

13. Clinic for Infectiology and Hospital Hygiene, Cantonal Hospital St Gallen , St Gallen , Switzerland

14. Division of Infectious Diseases, Regional Hospital Lugano , Lugano , Switzerland

15. Service for Infectious Diseases, Lausanne University Hospital , Lausanne , Switzerland

Abstract

Abstract Background Studying human immunodeficiency virus type 1 (HIV-1) superinfection is important to understand virus transmission, disease progression, and vaccine design. But detection remains challenging, with low sampling frequencies and insufficient longitudinal samples. Methods Using the Swiss HIV Cohort Study (SHCS), we developed a molecular epidemiology screening for superinfections. A phylogeny built from 22 243 HIV-1 partial polymerase sequences was used to identify potential superinfections among 4575 SHCS participants with longitudinal sequences. A subset of potential superinfections was tested by near-full-length viral genome sequencing (NFVGS) of biobanked plasma samples. Results Based on phylogenetic and distance criteria, 325 potential HIV-1 superinfections were identified and categorized by their likelihood of being detected as superinfections due to sample misidentification. NFVGS was performed for 128 potential superinfections; of these, 52 were confirmed by NFVGS, 15 were not confirmed, and for 61 sampling did not allow confirming or rejecting superinfection because the sequenced samples did not include the relevant time points causing the superinfection signal in the original screen. Thus, NFVGS could support 52 of 67 adequately sampled potential superinfections. Conclusions This cohort-based molecular approach identified, to our knowledge, the largest population of confirmed superinfections, showing that, while rare with a prevalence of 1%–7%, superinfections are not negligible events.

Funder

Swiss National Science Foundation

SHCS Research Foundation

Yvonne Jacob Foundation

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

Reference40 articles.

1. HIV is not transmitted under fully suppressive therapy: the Swiss Statement—eight years later;Vernazza;Swiss Med Wkly,2016

2. Risk of HIV transmission in discordant couples;Garnett;Lancet,2008

3. HIV superinfection: myth or reality?;Vernazza;Schweiz Med Wochenschr,2000

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