학술논문
Impact of the mutational load on the virological response to a first-line rilpivirine-based regimen.
Document Type
article
Author
Dimeglio, Chloé; Raymond, Stéphanie; Nicot, Florence; Jeanne, Nicolas; Carcenac, Romain; Lefebvre, Caroline; Izopet, Jacques; Roussel, C; Guillou-Guillemette, H Le; Alloui, C; Bettinger, D; Pallier, C; Fleury, H; Bellecave, P; Recordon-Pinson, P; Payan, C; Vallet, S; Vabret, A; Dina, J; Henquell, C; Mirand, A; Bouvier-Alias, M; de Rougemont, A; Si-Mohammed, A; Santos, G Dos; Morand, P; Signori-Schmuck, A; Bocket, L; Rogez, S; Andre, P; Tardy, JC; Trabaud, MA; Tamalet, C; Delamare, C; Montes, B; Schvoerer, E; Jeulin, H; Ferré, V; Rodallec, A; Guen, L Le; Cottalorda, J; Guinard, J; Guiguon, A; Descamps, D; Charpentier, C; Visseaux, B; Peytavin, G; Krivine, A; Bouviers-Alias, M; Avettand-Fenoel, V; Marcelin, AG; Calvez, V; Soulié, C; Wirden, M; Morand-Joubert, L; Lambert-Niclot, S; Fofana, D; Delaugerre, C; Chaix, ML; Mahjoub, N; Amiel, C; Schneider, V; Giraudeau, G; Beby-Defaux, A; Brodard, V; Maillard, A; Plantier, JC; Mourez, T; Leoz, M; Chaplain, C; Bourlet, T; Fafi-Kremer, S; Stoll-Keller, F; Schmitt, MP; Barth, H; Yerly, S; Poggi, C; Izopet, J; Raymond, S; Barin, F; Chaillon, A; Marque-Juillet, S; Roque-Afonso, AM; Haïm-Boukobza, S; Flandre, P; Grudé, M; Assoumou, L; Costagliola, D
Source
Journal of Antimicrobial Chemotherapy. 74(3)
Subject
Language
Abstract
ObjectivesTo 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 methodsFour 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.ResultsThe mutational load at baseline was the only variable linked to the VR at 12 months (P 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).ConclusionsThere 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