HIV-phyloTSI: subtype-independent estimation of time since HIV-1 infection for cross-sectional measures of population incidence using deep sequence data.

Golubchik, Tanya; Abeler-Dörner, Lucie; Hall, Matthew; Wymant, Chris; Bonsall, David; Macintyre-Cockett, George; Thomson, Laura; Baeten, Jared M; Celum, Connie L; Galiwango, Ronald M; +40 more...Kosloff, Barry; Limbada, Mohammed; Mujugira, Andrew; Mugo, Nelly R; Gall, Astrid; Blanquart, François; Bakker, Margreet; Bezemer, Daniela; Ong, Swee Hoe; Albert, Jan; Bannert, Norbert; Fellay, Jacques; Gunsenheimer-Bartmeyer, Barbara; Günthard, Huldrych F; Kivelä, Pia; Kouyos, Roger D; Meyer, Laurence; Porter, Kholoud; van Sighem, Ard; van der Valk, Mark; Berkhout, Ben; Kellam, Paul; Cornelissen, Marion; Reiss, Peter; Ayles, HelenORCID logo; Burns, David N; Fidler, Sarah; Grabowski, Mary Kate; Hayes, RichardORCID logo; Herbeck, Joshua T; Kagaayi, Joseph; Kaleebu, PontianoORCID logo; Lingappa, Jairam R; Ssemwanga, Deogratius; Eshleman, Susan H; Cohen, Myron S; Ratmann, Oliver; Laeyendecker, Oliver; Fraser, Christophe; and HPTN 071 (PopART) Phylogenetics protocol team, the BEEHIVE conso (2025) HIV-phyloTSI: subtype-independent estimation of time since HIV-1 infection for cross-sectional measures of population incidence using deep sequence data. BMC bioinformatics, 26. p. 212. ISSN 1471-2105 DOI: 10.1186/s12859-025-06189-y
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BACKGROUND: Estimating the time since HIV infection (TSI) at population level is essential for tracking changes in the global HIV epidemic. Most methods for determining TSI give a binary classification of infections as recent or non-recent within a window of several months, and cannot assess the cumulative impact of an intervention.

RESULTS: We developed a Random Forest Regression model, HIV-phyloTSI, which combines measures of within-host diversity and divergence to generate continuous TSI estimates directly from viral deep-sequencing data, with no need for additional variables. HIV-phyloTSI provides a continuous measure of TSI up to 9 years, with a mean absolute error of less than 12 months overall and less than 5 months for infections with a TSI of up to a year. It performs equally well for all major HIV subtypes based on data from African and European cohorts.

CONCLUSIONS: We demonstrate how HIV-phyloTSI can be used for incidence estimates on a population level.


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