A Low Level of Darunavir Resistance-Associated Mutation Emergence in Patients With Virological Failure During Long-term Use of Darunavir in People With HIV. The ANRS CO3 Aquitaine Cohort

Hélène Chaussade; Camille Tumiotto; Fabien Le Marec; Olivier Leleux; Lucile Lefèvre; Estibaliz Lazaro; Marie-Edith Lafon; Elsa Nyamankolly; Pierre Duffau; Didier Neau; Pantxika Bellecave; Fabrice Bonnet

doi:10.1093/ofid/ofaa567

A Low Level of Darunavir Resistance-Associated Mutation Emergence in Patients With Virological Failure During Long-term Use of Darunavir in People With HIV. The ANRS CO3 Aquitaine Cohort

Open Forum Infect Dis. 2020 Nov 19;7(12):ofaa567. doi: 10.1093/ofid/ofaa567. eCollection 2020 Dec.

Authors

Affiliations

¹ CHU Bordeaux, Services de Médecine Interne et Maladies Infectieuses, Bordeaux, France.
² CHU Bordeaux, Virology Laboratory, Bordeaux, France.
³ Univ. Bordeaux, ISPED, Inserm, Bordeaux Population Health Research Center, Team MORPH3Eus, UMR, Bordeaux, France.
⁴ JANSSEN France, Issy-les-Moulineaux, France.
⁵ CHU Bordeaux, Services de Médecine Interne et Maladies Infectieuses, Pessac, France.
⁶ CHU Bordeaux, Service des Maladies Infectieuses et Tropicales, Bordeaux, France.

Abstract

Background: Ritonavir-boosted darunavir (DRV/r) is a protease inhibitor (PI) indicated for the treatment of naïve and pretreated HIV-infected patients since 2007. Our study aims to describe DRV/r-treated patients experiencing virological failure (VF) documented with HIV resistance testing.

Methods: Data from patients belonging to the ANRS CO3 Aquitaine Cohort treated with a regimen including DRV/r between February 2007 and December 2015 were analyzed. Baseline characteristics of patients experiencing VF (defined by 2 consecutive plasma viral loads >50 copies/mL) were compared with those without VF. We then described factors associated with VF as emergence of IAS DRV resistance-associated mutations (RAMs).

Results: Among the 1458 patients treated at least once with a DRV/r-based regimen, 270 (18.5%) patients experienced VF during follow-up, including 240 with at least 1 genotype resistance test (GRT). DRV RAMs were detected in 29 patients (12%). Among them, 25/29 patients had ≥2 DRV RAMs before DRV/r initiation, all of whom had experienced VF during previous PI treatments. For 18/29, DRV/r was maintained after VF, and controlled viremia was restored after modification of DRV-associated antiretroviral molecules or increased DRV dose. Finally, only 6/29 patients selected new DRV RAMs after DRV/r initiation. All of these experienced previous VFs while on other PIs.

Conclusions: These results highlight the efficacy and robustness of DRV/r, as the emergence of DRV RAMs appeared in <0.4% of patients receiving a DRV/r-based regimen in our large cohort.

Keywords: HIV-1; darunavir; genotype; mutation rate.