Therapeutic Drug Monitoring of Long-Acting Cabotegravir and Rilpivirine in a National Cohort of People With HIV-1: First Results From the ANRS-MIE CARLAPOP Study

作者：Nadège Néant, Minh Lê, Stéphane Bouchet, Jennifer Lagoutte‐Renosi, Matthieu Grégoire, François Parant, Nicolas Venisse, Sébastien Lalanne, F. Lemaı̂tre, Patrice Muret, Quentin Renou, Alexandre Destère, Peggy Gandia, Philippe Flandre, Gilles Peytavin, Caroline Solas, for the ANRS-MIE-CARLAPOP Study Group, B. Bailly, Vincent Gendrin, Timothée Klopfenstein, Souheil Zayet, F Bozon, Anne‐Sophie Brunel, Bruno Hoën, Laurent Hustache‐Mathieu, Mojgane Hemssamfar, Fabrice Bonnet, Lionel Piroth, Marielle Buisson, Sophie Mahy, Michel Duong, Mary-Anne Trabaud, Dulce Alfaiate, Agathe Becker, Evelyne Braun, Florence M. Brunel, Matthieu Godinot, Thomas Perpoint, Clément Javaux, Philippe Colson, Anne Motte, Veronique Obry‐Roguet, Sylvie Brégigeon, Olivia Faucher‐Zaegel, Hélène Laroche, Maeva Dos Santos, Isabelle Ravaux, Catherine Dhiver, Christelle Tomei, Amélie Menard, Matthieu Million, Patrick Philibert, Christina Psomas, Simona-Loredana Berbescu, Catherine Michel, Thomas Drumel, Clotilde Allavena, Eric Billaud, Sabelline Bouchez, Cécile Brunet-Cartier, Colin Deschanvres, F. Raffi, Véronique Reliquet, Gwennaelle Querne, Cécile Mear-Passard, Antoine Asquier-Khati, Camille Moyon, Virginie Beslon, Lio Collias, Vincent Cálvez, Diane Descamps, Valentine Marie Ferré, Yazdanpanah Yazdan, Jade Ghosn, Valérie Pourcher, Marc‐Antoine Valantin, David Plainchamp, François Bénézit, Cédric Arvieux, Christine Cheneau, Axel Ursenbach, Baptiste Hoellinger, C Mélounou, David Rey, Yves Hansmann · 发表于：Clinical Infectious Diseases · 年份：2025 · DOI：10.1093/cid/ciaf385 · 被引用次数：5 · 研究领域：HIV-related health complications and treatments、HIV/AIDS drug development and treatment、Pharmacovigilance and Adverse Drug Reactions

BACKGROUND: The impact of pharmacokinetic variability of cabotegravir (CAB) and rilpivirine (RPV) long-acting (LA) injectable therapy on virological outcomes remains controversial. This study aimed to characterize the variability of CAB and RPV trough concentrations (Ctrough) and to identify the predictors of suboptimal exposure and virologic failure (VF) in a large real-world cohort. METHODS: We conducted a multicenter observational study including people with human immunodeficiency virus type 1 (HIV-1) initiating LA-CAB/RPV as maintenance therapy from January to December 2022, in whom CAB and RPV plasma Ctrough were determined as part of therapeutic drug monitoring (TDM). RESULTS: A total of 1674 CAB and 1687 RPV Ctrough measurements were collected from 736 people with HIV-1 (PWH). Significant interindividual variability in concentrations was observed. At month 1/month 3, 20%-30% of PWH had Ctrough <1120 ng/mL for CAB and 32 ng/mL for RPV. Predictors of lower Ctrough were body mass index (BMI) ≥30 kg/m2 and female sex at month 1, and only male sex at steady state. After a median follow-up of 12 (interquartile range, 9-16) months, VF occurred in 2.5% of PWH. At month 6 and month 12, VF was significantly associated with the presence of at least 2 risk factors (obesity, suboptimal Ctrough) (odds ratio [OR], 4.6, P = .047; OR, 5.15, P = .014), and CD4 nadir (OR, 0.56, P = .008; OR, 0.5, P = .001). CONCLUSIONS: Our large real-world study confirms significant variability in CAB a...