1. Prevalence and clinical impact of minority resistant variants in patients failing an integrase inhibitor-based regimen by ultra-deep sequencing
- Author
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Eve Todesco, Maxime Grude, Sidonie Lambert-Niclot, A G Marcelin, Nathalie Désiré, Diane Descamps, Gilles Peytavin, Minh Patrick Lê, Christine Katlama, Philippe Flandre, Charlotte Charpentier, Thuy Van Nguyen, Marc Wirden, D. B. Fofana, Laurence Morand-Joubert, Vincent Calvez, Gestionnaire, Hal Sorbonne Université, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Virologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Virologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Virologie [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], and Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière]
- Subjects
Adult ,Male ,0301 basic medicine ,Microbiology (medical) ,Paris ,medicine.medical_specialty ,Genotyping Techniques ,[SDV]Life Sciences [q-bio] ,030106 microbiology ,Integrase inhibitor ,HIV Infections ,Drug resistance ,03 medical and health sciences ,chemistry.chemical_compound ,symbols.namesake ,Antiretroviral Therapy, Highly Active ,Internal medicine ,Drug Resistance, Viral ,Prevalence ,medicine ,Humans ,Pharmacology (medical) ,HIV Integrase Inhibitors ,Treatment Failure ,Pharmacology ,Sanger sequencing ,Elvitegravir ,business.industry ,High-Throughput Nucleotide Sequencing ,Middle Aged ,Raltegravir ,Resistance mutation ,[SDV] Life Sciences [q-bio] ,Regimen ,Infectious Diseases ,chemistry ,Dolutegravir ,HIV-1 ,symbols ,Female ,business ,medicine.drug - Abstract
Background Integrase strand transfer inhibitors (INSTIs) are recommended by international guidelines as first-line therapy in antiretroviral-naive and -experienced HIV-1-infected patients. Objectives This study aimed at evaluating the prevalence at failure of INSTI-resistant variants and the impact of baseline minority resistant variants (MiRVs) on the virological response to an INSTI-based regimen. Methods Samples at failure of 134 patients failing a raltegravir-containing (n = 65), an elvitegravir-containing (n = 20) or a dolutegravir-containing (n = 49) regimen were sequenced by Sanger sequencing and ultra-deep sequencing (UDS). Baseline samples of patients with virological failure (VF) (n = 34) and of those with virological success (VS) (n = 31) under INSTI treatment were sequenced by UDS. Data were analysed using the SmartGene platform, and resistance was interpreted according to the ANRS algorithm version 27. Results At failure, the prevalence of at least one INSTI-resistant variant was 39.6% by Sanger sequencing and 57.5% by UDS, changing the interpretation of resistance in 17/134 (13%) patients. Among 53 patients harbouring at least one resistance mutation detected by both techniques, the most dominant INSTI resistance mutations were N155H (45%), Q148H/K/R (23%), T97A (19%) and Y143C (11%). There was no difference in prevalence of baseline MiRVs between patients with VF and those with VS. MiRVs found at baseline in patients with VF were not detected at failure either in majority or minority mutations. Conclusions UDS is more sensitive than Sanger sequencing at detecting INSTI MiRVs at treatment failure. The presence of MiRVs at failure could be important to the decision to switch to other INSTIs. However, there was no association between the presence of baseline MiRVs and the response to INSTI-based therapies in our study.
- Published
- 2018