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 INFECTIOUS DISEASES(2020)

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摘要
Background. Ritonavir-boosted darunavir (DRV/r) is a protease inhibitor (PI) indicated for the treatment of naive 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 be- tween February 2007 and December 2015 were analyzed. Baseline characteristics of patients experiencing VF (defined by 2 consecutive plasma viral loads >50 copies/mI,) 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 Pls.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.
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关键词
darunavir, HIV-1, genotype, mutation rate
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