Genetic diversity from proviral DNA as a proxy for time since HIV-1 infection

Marius Zeeb; Paul Frischknecht; Michael Huber; Corinne D Schenkel; Kathrin Neumann; Christine Leeman; Julia Notter; Andri Rauch; Marcel Stöckle; Matthias Cavassini; Enos Bernasconi; Dominique L Braun; Huldrych F Günthard; Karin J Metzner; Roger D Kouyos

doi:10.1093/infdis/jiae149

Genetic diversity from proviral DNA as a proxy for time since HIV-1 infection

J Infect Dis. 2024 Mar 20:jiae149. doi: 10.1093/infdis/jiae149. Online ahead of print.

Authors

Marius Zeeb^{1

2}, Paul Frischknecht¹, Michael Huber², Corinne D Schenkel¹, Kathrin Neumann¹, Christine Leeman¹, Julia Notter³, Andri Rauch⁴, Marcel Stöckle^{5

6}, Matthias Cavassini⁷, Enos Bernasconi⁸, Dominique L Braun¹, Huldrych F Günthard^{1

2}, Karin J Metzner^{1

2}, Roger D Kouyos^{1

2}

Affiliations

¹ Department. of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, 8091 Zurich, Switzerland.
² Institute of Medical Virology, University Zurich, 8057 Zurich, Switzerland.
³ Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St Gallen, 9007 St. Gallen, Switzerland.
⁴ Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland.
⁵ Division of Infectious Diseases & Hospital Epidemiology, University Hospital Basel, 4031 Basel, Switzerland.
⁶ Medical Faculty, University of Basel, 4031 Basel, Switzerland.
⁷ Division of Infectious Diseases, University Hospital Lausanne, University of Lausanne, 1011 Lausanne, Switzerland.
⁸ Division of infectious diseases, Ente Ospedaliero Cantonale, Lugano, University of Geneva and University of Southern Switzerland, 6900 Lugano, Switzerland.

PMID: 38507572
DOI: 10.1093/infdis/jiae149

Abstract

HIV-1 RNA genetic diversity predicts time since infection which is important for clinical care and research. It's unclear, however, whether proviral DNA genetic diversity sampled under suppressive antiretroviral therapy can be used for this purpose. We tested whether proviral genetic diversity from NGS sequences predicts time since infection and recency in 221 people with HIV-1 with known infection time. Proviral diversity was significantly associated with time since infection (p<5*10-07, R2 up to 25%) and predictive of treatment initiation during recent infection (AUC-ROC up to 0.85). This shows the utility of proviral genetic diversity as a proxy for time since infection.

Keywords: HIV-1; infection recency; next-generation sequencing; proviral diversity; time since infection.