Real-world trough concentrations and effectiveness of long-acting cabotegravir and rilpivirine: a multicenter prospective observational study in Switzerland
Paul Thoueille, Susana Alves Saldanha, Fabian Schaller, Eva Choong, Aline Munting, Matthias Cavassini, Dominique L. Braun, Huldrych F. Günthard, Katharina Kusejko, Bernard Surial, Hansjakob Furrer, Andri Rauch, Mathieu Rougemont, Pilar Ustero, Alexandra Calmy, M Stöckle, Catia Marzolini, Caroline Di Benedetto, Enos Bernasconi, Patrick Schmid, Rein Jan Piso, Pascal André, François Girardin, Monia Guidi, Thierry Buclin, Laurent A. Décosterd, Irène A. Abela, Karoline Aebi‐Popp, A Anagnostopoulos, M Battegay, Enos Bernasconi, Dominique L. Braun, H C Bucher, Alexandra Calmy, Matthias Cavassini, Angela Ciuffi, G Dollenmaier, Matthias Egger, Luigia Elzi, Jan Fehr, Jacques Fellay, Hansjakob Furrer, C A Fux, Huldrych F. Günthard, Anna Hachfeld, D Haerry, Barbara Hasse, Hans H. Hirsch, Matthias Hoffmann, Irène Hösli, M Huber, David Jackson‐Perry, C R Kahlert, Laurent Kaiser, Olivia Keiser, Thomas Klimkait, Roger D. Kouyos, Helen Kovari, Katharina Kusejko, Niklaus Daniel Labhardt, Karoline Leuzinger, Begoña Martínez de Tejada, Catia Marzolini, Karin J. Metzner, Nora Müller, Johannes Nemeth, Dunja Nicca, Julia Notter, P Paioni, G Pantaleo, Matthieu Perreau, Andri Rauch, Luisa Salazar‐Vizcaya, Patrick Schmid, Roberto F. Speck, M Stöckle, Philip Tarr, Alexandra Trkola, Gilles Wandeler, Maja Weisser, Sabine Yerly
Abstract
Background: The efficacy and tolerability of long-acting cabotegravir and rilpivirine were demonstrated in Phase III trials. However, low concentrations combined with other risk factors have been associated with an increased risk of virologic failure. This study aims to verify whether drug concentrations measured in a real-world setting are consistent with those previously reported. Methods: SHCS-879 is a nationwide observational study within the Swiss HIV Cohort Study for the monitoring of people with HIV (PWH) on long-acting cabotegravir plus rilpivirine. Samples were collected from March 2022 to March 2023. Findings: Overall, 725 samples were obtained from 186 PWH. Our data show a large inter-individual variability in cabotegravir and rilpivirine concentrations, with some individuals exhibiting repeatedly low concentrations. Rilpivirine trough concentrations were consistent with those from Phase III trials, while cabotegravir concentrations were lower. The first concentrations quartile was only slightly above the target of 664 ng/mL. Exploratory statistical analyses found 35% (p < 0·01) lower cabotegravir trough in males compared to females. Overall, 172 PWH (92%) remained suppressed and three experienced virologic failures (1·6%), of those, two had sub-optimal drug exposure. No association was found between low trough levels and detectable viral load. Interpretation: Real-world cabotegravir concentrations are substantially lower than previously reported. However, these concentrations appear sufficient to ensure sustained virological suppression in almost every PWH. These reassuring data challenge the rather conservative thresholds adopted to date, which may raise unnecessary concerns. Yet, our study reveals that some PWH have repeatedly very low drug levels, for reasons that remain to be elucidated. Funding: 324730_192449. This study received no support from pharmaceutical industries. This study was performed within the framework of the Swiss HIV Cohort Study, supported by the Swiss National Science Foundation (grant #201369), by SHCS project #879, and by the SHCS research foundation. The SHCS data were gathered by the Five Swiss University Hospitals, two Cantonal Hospitals, 15 affiliated hospitals and 36 private physicians (listed in http://www.shcs.ch/180-health-care-providers).