Limited Weight Impact After Switching From Boosted Protease Inhibitors to Dolutegravir in Persons With Human Immunodeficiency Virus With High Cardiovascular Risk: A Post Hoc Analysis of the 96-Week NEAT-022 Randomized Trial
Laura Waters, Lambert Assoumou, Ana Gonzalez‐Cordón, Stefano Rusconi, Peré Domingo, Mark Gompels, Stephane de Wit, François Raffi, Christoph Stephan, Mar Masiá, Jürgen K. Rockstroh, Christine Katlama, Georg M. N. Behrens, Graeme Moyle, Margaret Johnson, Julie Fox, Hans‐Jürgen Stellbrink, Giovanni Guaraldi, Éric Florence, Stefan Eßer, José M. Gatell, Anton Pozniak, Estebán Martínez, for the NEAT 022 Study Group, Linos Vandekerckhove, Els Caluwé, Stephane de Wit, Coca Necsoi, Éric Florence, Maartje Van Frankenhuijsen, François Raffi, Clotilde Allavena, Véronique Reliquet, David Boutoille, Morane Cavellec, Elisabeth André‐Garnier, Audrey Rodallec, Thierry Le Tourneau, J. Connault, Jean‐Michel Molina, Samuel Ferret, Miresta Prévilon, Yazdan Yazdanpanah, Roland Landman, Véronique Joly, Adriana Pinto, Christine Katlama, Fabienne Caby, Nadine Ktorza, Luminita Schneider, Christoph Stephan, Timo Wolf, Gundolf Schüttfort, Juergen Rockstroh, Jan‐Christian Wasmuth, Carolynne Schwarze‐Zander, Christoph Boesecke, Hans‐Jürgen Stellbrink, Christian Hoffmann, Michael Sabranski, Stephan Esser, Robert Jablonka, Heidi Wiehler, Georg M. N. Behrens, Matthias Stoll, Gerrit Ahrenstorf, Giovanni Guaraldi, Giulia Nardini, Barbara Beghetto, Antonella D’Arminio Montforte, Teresa Bini, Viola Cogliandro, Massimo Di Pietro, Francesco Maria Fusco, Massimo Galli, Stefano Rusconi, Andrea Giacomelli, Paola Meraviglia, Estebán Martínez, Ana Gonzalez‐Cordón, José María Gatell, Berta Torres, Peré Domingo, Gràcia Mateo, Mar Gutierrez, Joaquín Portilla, Esperanza Merino, Sergio Reus, Vicente Boix, Mar Masiá, Félix Gutiérrez, Sergio Padilla, Bonaventura Clotet, Eugènia Negredo, Anna Bonjoch, José L. Casado, Sara Bañón-Escandell, José Sabán, Africa Duque, Daniel Podzamczer
Abstract
BACKGROUND: In the NEAT022 trial, virologically suppressed persons with human immunodeficiency virus (HIV) at high cardiovascular risk switching from protease inhibitors to dolutegravir either immediately (DTG-I) or after 48 weeks (DTG-D) showed noninferior virological suppression and significant lipid and cardiovascular disease risk reductions on switching to dolutegravir relative to continuing protease inhibitors. METHODS: In post hoc analysis, major endpoints were 48-week and 96-week weight and body mass index (BMI) changes. Factors associated with weight/BMI changes within the first 48 weeks of DTG exposure, proportion of participants by category of percentage weight change, proportions of BMI categories over time, and impact on metabolic outcomes were also assessed. RESULTS: Between May 2014 and November 2015, 204 (DTG-I) and 208 (DTG-D) participants were included. Weight significantly increased (mean, +0.810 kg DTG-I arm, and +0.979 kg DTG-D arm) in the first 48 weeks postswitch, but remained stable from 48 to 96 weeks in DTG-I arm. Switching from darunavir, White race, total to high-density lipoprotein cholesterol ratio <3.7, and normal/underweight BMI were independently associated with higher weight/BMI gains. The proportion of participants with ≥5% weight change increased similarly in both arms over time. The proportions of BMI categories, use of lipid-lowering drugs, diabetes and/or use of antidiabetic agents, and hypertension and/or use of antihypertensive agents did not change within or between arms at 48 and 96 weeks. CONCLUSIONS: Switching from protease inhibitors to dolutegravir in persons with HIV with high cardiovascular risk led to modest weight gain limited to the first 48 weeks, which involved preferentially normal-weight or underweight persons and was not associated with negative metabolic outcomes. CLINICAL TRIALS REGISTRATION: NCT02098837 and EudraCT 2013-003704-39.