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Pyngottu, Ashima; Scherrer, Alexandra U; Kouyos, Roger; Huber, Michael; Hirsch, Hans; Perreau, Matthieu; Yerly, Sabine; Calmy, Alexandra; Cavassini, Matthias; Stöckle, Marcel; Furrer, Hansjakob; Vernazza, Pietro; Bernasconi, Enos; Günthard, Huldrych F; 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; Martinez de Tejada, B; Marzolini, C; Metzner, K J; Müller, N; Nicca, D; Paioni, P; Pantaleo, G; Perreau, M; Rauch, A; Rudin, C; Scherrer, A U; Schmid, P; Speck, R; Stöckle, M; Tarr, P; Trkola, A; Vernazza, P; Wandeler, G; Weber, R; Yerly, S
Clinical infectious diseases, 10/2021, Volume: 73, Issue: 7Journal Article
Abstract Background Integrase strand transfer inhibitors (InSTIs) are recommended for first-line treatment of persons with human immunodeficiency virus (HIV). We identified risk factors, including baseline minor InSTI resistance mutations, for treatment failure of InSTI-based regimens. Methods We studied time-to-treatment failure and time to viral suppression among 1419 drug-naive patients in the Swiss HIV Cohort Study. We performed Cox regression models adjusted for demographic factors, baseline HIV RNA/CD4 cell counts, AIDS-defining events, and the type of InSTI. In 646 patients with a baseline genotypic resistance test of the integrase, we studied the impact of minor integrase resistance mutations. Results We observed 121 virological failures during 18 447 person-years of follow-up. A baseline viral load ≥100 000 copies/mL (multivariable hazard ratio mHR, 2.2; 95% confidence interval CI, 1.3–3.6) and an AIDS-defining event (mHR, 1.8; 95% CI. 1.1–3.0) were associated with treatment failure. CD4 counts between 200 and 500 cells/µL (mHR, 0.5; 95% CI, .3–.8) and >500 cells/µL (mHR, 0.4; 95% CI, .2–.7) were protective. Time to suppression was shorter in lower viral load strata (mHR, 0.7; 95% CI, .6–.8) and in dolutegravir-based therapy (mHR, 1.2; 95% CI, 1.0–1.4). Minor resistance mutations were found at baseline in 104 of 646 (16%) patients with no effect on treatment outcome. Conclusions Factors associated with treatment failure on InSTI-based first-line regimen remained similar to those of older treatments, in particular high viral load and low CD4 counts.
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