Pre-treatment resistance to integrase inhibitors in the Swiss HIV Cohort Study from 1995 to 2025

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ID: 321533
2026
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Abstract
Abstract Background Studies in Switzerland and other settings have reported minimal pre-treatment Integrase strand transfer inhibitor (INSTI) resistance, but many were conducted before widespread use of INSTIs or are limited regarding data availability and representativeness. Consequently, many questions remain regarding the transmissibility of INSTI resistance mutations. Methods In sequences predating ART initiation collected in the Swiss HIV cohort study (SHCS) resistance database, we assess INSTI drug resistance mutations (DRMs) using the Stanford HIVdb algorithm. We use Bayesian regression models to assess INSTI DRM trends, as well as epidemiological clustering. Models are adjusted for age, sex, HIV subtype, and time as a spline, with random effects for SHCS center of registration and sequencing laboratory. Results 3’704 SHCS participants had an integrase sequence before ART initiation; 213 (5.8%) had INSTI DRMs, including 11 (0.3%) with major INSTI DRM(s). The most common DRMs were the polymorphic accessory INSTI DRMs E157Q, T97A, and L74M. There was no change in the probability of detecting INSTI DRM(s) over the past three decades. Epidemiological clustering was similar between individuals with pre-ART INSTI DRM(s) and those without; however, the clusters they formed were smaller, particularly before 2010. Conclusions This study demonstrates that in Switzerland, pre-ART INSTI DRMs are very rare despite INSTIs being used for more than 10 years. In cases where pre-ART INSTI DRMs are detected, information on the context in which they emerged is rarely available, highlighting the need for continued genetic surveillance, particularly in face of increasing numbers of individuals with INSTI resistance globally.
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Authors Tom Loosli, Marco Labarile, Nanina Anderegg, Paul Frischknecht, Nuri Han, Sandra E Chaudron, Gilles Wandeler, Marcel Stoeckle, Matthias Cavassini, Alexandra Calmy, Patrick Schmid, Luigia Elzi, Irène A. Abela, Michael Huber, Karoline Leuzinger, Sabine Yerly, Matthieu Perreau, Huldrych F. Günthard, Roger D. Kouyos
Journal Open forum infectious diseases
Year 2026
DOI
10.1093/ofid/ofag435
URL
https://doi.org/10.1093/ofid/ofag435
Keywords Keywords not found

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