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Impact of the mutational load on the virological response to a first-line rilpivirine-based regimen

Abstract : Objectives: To determine how the load of rilpivirine-resistant variants (mutational load) influences the virological response (VR) of HIV-1-infected patients to a rilpivirine-based first-line regimen. Patients and methods: Four hundred and eighty-nine patients infected with HIV-1 whose reverse transcriptase gene had been successfully resistance genotyped using next-generation sequencing were given a first-line regimen containing rilpivirine. Variables associated with the VR at 12 months were identified using a logistic model. The results were used to build a multivariate model for each mutational load threshold and the R2 variations were analysed to identify the mutational load threshold that best predicted the VR. Results: The mutational load at baseline was the only variable linked to the VR at 12 months (P < 0.01). The VR at 12 months decreased from 96.9% to 83.4% when the mutational load was >1700 copies/mL and to 50% when the mutational load was > 9000 copies/mL. The threshold of 9000 copies/mL was associated with the VR at 12 months with an OR of 36.7 (95% CI 4.7-285.1). The threshold of 1700 copies/mL was associated with the VR at 12 months with an OR of 7.2 (95% CI 1.4-36.8). Conclusions: There is quantifiable evidence that determining a mutational load threshold can be used to identify those patients on a first-line regimen containing rilpivirine who are at risk of virological failure. The clinical management of HIV-infected patients can be improved by evaluating the frequency of mutant variants at a threshold of < 20% together with the plasma HIV-1 viral load at the time of resistance genotyping.
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https://hal-normandie-univ.archives-ouvertes.fr/hal-02154171
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Submitted on : Wednesday, June 12, 2019 - 5:34:26 PM
Last modification on : Tuesday, March 15, 2022 - 11:29:34 AM

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Chloé Dimeglio, Stéphanie Raymond, Florence Nicot, Nicolas Jeanne, Romain Carcenac, et al.. Impact of the mutational load on the virological response to a first-line rilpivirine-based regimen. Journal of Antimicrobial Chemotherapy, Oxford University Press (OUP), 2018, 74 (3), pp.718-721. ⟨10.1093/jac/dky495⟩. ⟨hal-02154171⟩

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