Impact of Integrase Inhibitors on Cardiovascular Disease Events in People With Human Immunodeficiency Virus Starting Antiretroviral Therapy
Bernard Surial, Frédérique Chammartin, José Damas, Alexandra Calmy, David Haerry, M Stöckle, Patrick Schmid, Enos Bernasconi, Christoph A. Fux, Philip Tarr, Huldrych F. Günthard, Gilles Wandeler, Andri Rauch, the Swiss HIV Cohort Study, 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, Christoph A. Fux, Huldrych F. Günthard, Anna Hachfeld, David Haerry, Barbara Hasse, Hans H. Hirsch, Matthew Hoffmann, Irène Hösli, M Huber, David Jackson‐Perry, Christian R. Kahlert, Laurent Kaiser, Olivia Keiser, Thomas Klimkait, Roger D. Kouyos, Helen Kovari, Katharina Kusejko, Niklaus Daniel Labhardt, Karoline Leuzinger, Tejada B Martinez de, 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: Integrase strand transfer inhibitors (INSTIs) have been associated with an increased risk for cardiovascular disease (CVD) events. We investigated the impact of starting INSTI-based antiretroviral therapy (ART) on CVD events among treatment-naïve people with human immunodeficiency virus using a target trial framework, which reduces the potential for confounding and selection bias. METHODS: We included Swiss HIV Cohort Study participants who were ART-naïve after May 2008, when INSTIs became available in Switzerland. Individuals were categorized according to their first ART regimen (INSTI vs other ART) and were followed from ART start until the first of CVD event (myocardial infarction, stroke, or invasive cardiovascular procedure), loss to follow-up, death, or last cohort visit. We calculated hazard ratios and risk differences using pooled logistic regression models with inverse probability of treatment and censoring weights. RESULTS: Of 5362 participants (median age 38 years, 21% women, 15% of African origin), 1837 (34.3%) started INSTI-based ART, and 3525 (65.7%) started other ART. Within 4.9 years (interquartile range, 2.4-7.4), 116 CVD events occurred. Starting INSTI-based ART was not associated with an increased risk for CVD events (adjusted hazard ratio, 0.80; 95% confidence interval [CI], .46-1.39). Adjusted risk differences between individuals who started INSTIs and those who started other ART were -0.17% (95% CI, -.37 to .19) after 1 year, -0.61% (-1.54 to 0.22) after 5 years, and -0.71% (-2.16 to 0.94) after 8 years. CONCLUSIONS: In this target trial emulation, we found no difference in short- or long-term risk for CVD events between treatment-naïve people with human immunodeficiency virus who started INSTI-based ART and those on other ART.