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

Title: Impact of the mutational load on the virological response to a first-line rilpivirine-based regimen.
Authors: 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, vol 74, iss 3
Publisher Information: eScholarship, University of California
Publication Year: 2019
Collection: University of California: eScholarship
Subject Terms: Clinical Research; Genetics; HIV/AIDS; Infectious Diseases; Infection; Antiretroviral Therapy; Highly Active; Drug Resistance; Viral; Female; Genome; Genotype; HIV Infections; HIV-1; High-Throughput Nucleotide Sequencing; Humans; Male; Mutation; Rilpivirine; Treatment Outcome; Viral Load; French National Agency for Research on AIDS and Viral Hepatitis (ANRS) AC11 Resistance Study Group; Microbiology; Medical Microbiology; Pharmacology and Pharmaceutical Sciences
Subject Geographic: 718 - 721
Description: 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 < 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).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 < 20% together with the plasma HIV-1 viral load at the time of resistance genotyping.
Document Type: article in journal/newspaper
Language: unknown
Relation: qt51f9n6dx; https://escholarship.org/uc/item/51f9n6dx
DOI: 10.1093/jac/dky495
Availability: https://escholarship.org/uc/item/51f9n6dx; https://doi.org/10.1093/jac/dky495
Rights: public
Accession Number: edsbas.3703ED13
Database: BASE