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J Antimicrob Chemother. 2019 Mar 1;74(3):718-721. doi: 10.1093/jac/dky495.

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

Author information

1
INSERM U1043 - CNRS UMR5282 - Toulouse University Paul Sabatier, CPTP, Toulouse, France.
2
CHU de Toulouse, Hôpital Purpan, Laboratoire de Virologie, Toulouse, France.

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.

PMID:
30535228
DOI:
10.1093/jac/dky495

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