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

Golubchik, T; Abeler-Dörner, L; Hall, M; Wymant, C; Bonsall, D; Macintyre-Cockett, G; Thomson, L; Baeten, JM; Celum, CL; Galiwango, RM; +40 more...Kosloff, B; Limbada, M; Mujugira, A; Mugo, NR; Gall, A; Blanquart, F; Bakker, M; Bezemer, D; Ong, SH; Albert, J; Bannert, N; Fellay, J; Gunsenheimer-Bartmeyer, B; Günthard, HF; Kivelä, P; Kouyos, RD; Meyer, L; Porter, K; van Sighem, A; van der Valk, M; Berkhout, B; Kellam, P; Cornelissen, M; Reiss, P; Ayles, HORCID logo; Burns, DN; Fidler, S; Grabowski, MK; Hayes, RORCID logo; Herbeck, JT; Kagaayi, J; Kaleebu, PORCID logo; Lingappa, JR; Ssemwanga, D; Eshleman, SH; Cohen, MS; Ratmann, O; Laeyendecker, O; Fraser, C; HPTN 071 (PopART) Phylogenetics protocol team, the BEEHIVE conso and (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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