Impact of Human Immunodeficiency Virus Type 1 Minority Variants on the Virus Response to a Rilpivirine-Based First-line Regimen

Raymond, Stéphanie; Nicot, François; Pallier, C.; Bellecave, Pantxika; Maillard, Anne; Trabaud, Mary‐Anne; Morand‐Joubert, Laurence; Rodallec, Audrey; Amiel, Corinne; Mourez, Thomas; Bocket, Laurence; Beby‐Defaux, Agnès; Lambert-Niclot, Sidonie; Charpentier, Charlotte; Malvé, Brice; Mirand, Audrey; Marque-Juillet, Stéphanie; Signori-Schmück, Anne; Barin, Françis; Si-Mohamed, Ali; Fenoel, Véronique Avettand; Cálvez, Vincent; Sauné, Karine; Marcelin, Anne Geneviève; Rodriguez, Christophe; Descamps, Diane; Izopet, Jacques; Lagier, E; Roussel, Catherine; Guillou‐Guillemette, Hélène Le; Alloui, Chakib; Bettinger, Dominique; Fleury, Hervé; Reigadas, Sandrine; Recordon-Pinson, Patricia; Payan, Christopher; Vallet, Sophie; Vabret, Astrid; Dina, Julia; Henquell, Cécile; Bouvier‐Alias, Magali; Rougemont, Alexis de; Santos, Georges Dos; Morand, Patrice; Rogez, S.; André, Patrice; Tardy, J. C.; Trabaud, Mary‐Anne; Tamalet, Catherine; Delamare, Catherine; Montès, Brigitte; Schvoerer, Évelyne; Ferré, Virginie; André-Garnier, Élisabeth; Cottalorda, J.; Guinard, Jérôme; Guiguon, A.; Brun‐Vézinet, Françoise; Visseaux, Benoît; Peytavin, Gilles; Krivine, Anne; Avettand-Fènoël, Véronique; Soulié, Cathia; Wirden, Marc; Delaugerre, Constance; Chaix, Marie‐Laure; Schneider, Véronique; Giraudeau, G.; Defaux, A Beby-; Brodard, Véronique; Plantier, Jean‐Christophe; Chaplain, C.; Bourlet, Thomas; Fafi‐Kremer, Samira; Stoll‐Keller, Françoise; Schmitt, Marie-Paule; Barth, Hubert; Yerly, Sabine; Poggi, Cécile; Chaillon, Antoine; Roque–Afonso, Anne–Marie; Haïm-Boukobza, Stéphanie; Flandre, Philippe; Grudé, Maxime; Assoumou, Lambert; Costagliola, Dominique; Allègre, Thierry; Schmit, Jean‐Luc; Chennebault, Jean‐Marie; Bouchaud, Olivier; Magy‐Bertrand, N.; Delfraissy, Jean François; Dupon, M.; Morlat, Philippe; Néau, Didier; Ansart, Séverine; Jaffuel, S.; Verdon, Renaud; Jacomet, Christine; Lévy, Yves; Dominguez, Stéphanie; Chavanet, P.; Piroth, Lionel; Cabie, André; Leclercq, Pascale; Ajana, F.; Chéret, Antoine; Weinbreck, P.; Cotte, Laurent; Poizot‐Martin, Isabelle; Ravaud, I.; Berthou, Christian; Truchetet, F.; Grandidier, Michel; Reynes, Jacques; May, Thierry; Goehringer, François; Raffi, François; Dellamonica, P.; Prazuck, Thiérry; Hocqueloux, Laurent; Landman, Roland; Yazdanpanah,; Launay, Odile; Weiss, Laurence; Viard, Jean‐Paul; Katlama, Christine; Simon, Anne; Pm, Girard; Meynard, Jean-Luc; Molina, J M; Pialoux, Gilles; Hoën, Bruno; Goeger-Sow, M. T.; Lamaury, I.; Beaucaire, G.; Moal, G. Le; Jaussaud, R.; Rouger, C.; Michelet, Christian; Borsa-Lebas, F.; Caron, François; Khuong, M. A.; Lucht, F.; Rey, David; Calmy, Alexandra; Lafeuillade, Alain; Marchou, B.; Delobel, Pierre; Gras, Gabriel; Greder-Belan, A.; Vittecoq, D.; Teiche, E

doi:10.1093/cid/cix1070

Cited by 17 publications

(9 citation statements)

References 27 publications

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“…However, a recent study by Raymond S et al, using the NGS 454 GS-FLX system, showed that drug-resistant minority variants had no impact on the virological failure of treatment-naive patients to a rilpivirine-based regimen [23].…”

Section: Introductionmentioning

confidence: 99%

First evaluation of the Next-Generation Sequencing platform for the detection of HIV-1 drug resistance mutations in Belgium

et al. 2018

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IntroductionThe WHO urges action against the threat posed by HIV drug resistance. It is well known that the sensitivity of Next-Generation Sequencing (NGS) is greater than that of Sanger Sequencing (SS). The objective of this study was to evaluate the performance of the novel NGS HIV-1 drug resistance monitoring system.Materials & methodsNGS analyses were performed on 67 plasma samples from HIV-1 infected patients using the Sentosa SQ HIV Genotyping Assay from Vela-Dx. This kit was used on a semi-automated Ion Torrent-based platform. Sequences were compared to those obtained by SS. Samples were analysed in the same and in separate runs. Quality controls (QC) were added to control sequencing processes of protease (PRO), reverse transcriptase (RT) and integrase (INT) regions.ResultsOf the 41 analysed samples, 33 (80.5%) had identical drug resistance interpretation reports. Discrepant results were observed for eight samples. Five of them were only detected by NGS and had drug resistance mutations (DRMs) with an allelic frequency below the limit of detection of the SS method (between 6.3 to 20.5%). Two DRMs were only identified using the SS method. The sequences were similar in 98.2% of cases (counting variants as mismatches) and homologous in 99.9% if missed variants. Duplicated samples in a single run were similar in 95.7% (99.9%) of cases. Duplicated samples in two different runs were 98% (100%) homologous. QC results were manually assessed with a score of 340/340 for detection of DRMs in PRO and RT and 100% for INT sequencing.ConclusionsThis is the first preliminary evaluation in Belgium employing the Sentosa SQ HIV Genotyping Assay. The NGS appears to be a promising tool for the detection of DRMs in HIV-1 patients and showed a higher sensitivity compared to SS. Large studies assessing the clinical relevance of low frequency DRMs are needed.

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Section: Introductionmentioning

confidence: 99%

First evaluation of the Next-Generation Sequencing platform for the detection of HIV-1 drug resistance mutations in Belgium

et al. 2018

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“…Ultradeep sequencing technologies capable of detecting variants present at a frequency as low as 1% of the virus population, for example, next-generation sequencing (NGS), are slowly being introduced into clinical microbiology diagnostic laboratories. However, the evidence for the clinical significance of drug-resistant minority variants (DRMinVs) is contradictory, and more data are required to inform their interpretation in clinical management of HIV-infected individuals using validated assays and large-scale clinical studies [2][3][4][5][6][7][8][9][10].…”

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confidence: 99%

Determining the Origins of Human Immunodeficiency Virus Type 1 Drug-resistant Minority Variants in People Who Are Recently Infected Using Phylogenetic Reconstruction

Mbisa

Kirwan

Tostevin

et al. 2018

Clinical Infectious Diseases

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Background. Drug-resistant minority variants (DRMinVs) detected in patients who recently acquired human immunodeficiency virus type 1 (HIV-1) can be transmitted, generated de novo through virus replication, or technical errors. The first form is likely to persist and result in treatment failure, while the latter two could be stochastic and transient.Methods. Ultradeep sequencing of plasma samples from 835 individuals with recent HIV-1 infection in the United Kingdom was performed to detect DRMinVs at a mutation frequency between 2% and 20%. Sequence alignments including >110 000 HIV-1 partial pol consensus sequences from the UK HIV Drug Resistance Database (UK-HDRD), linked to epidemiological and clinical data from the HIV and AIDS Reporting System, were used for transmission cluster analysis. Transmission clusters were identified using Cluster Picker with a clade support of >90% and maximum genetic distances of 4.5% or 1.5%, the latter to limit detection to likely direct transmission events.Results. Drug-resistant majority variants (DRMajVs) were detected in 66 (7.9%) and DRMinVs in 84 (10.1%) of the recently infected individuals. High levels of clustering to sequences in UK-HDRD were observed for both DRMajV (n = 48; 72.7%) and DRMinV (n = 63; 75.0%) sequences. Of these, 43 (65.2%) with DRMajVs were in a transmission cluster with sequences that harbored the same DR mutation compared to only 3 (3.6%) sequences with DRMinVs (P < .00001, Fisher exact test). Evidence of likely direct transmission of DRMajVs was observed for 25/66 (37.9%), whereas none were observed for the DRMinVs (P < .00001).Conclusions. Using a densely sampled HIV-infected population, we show no evidence of DRMinV transmission among recently infected individuals.

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“…Second, the analyzed data was generated by research laboratories that adopted measures to improve the detection of low frequency variants, avoided samples with very low virus loads, and made their data publicly available. Indeed, previous studies have suggested that a five percent threshold is likely to be more reproducible in clinical settings [7,24,32,33].…”

Section: Discussionmentioning

confidence: 99%

Analysis of unusual and signature APOBEC-mutations in HIV-1 pol next-generation sequences

et al. 2020

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Impact of Human Immunodeficiency Virus Type 1 Minority Variants on the Virus Response to a Rilpivirine-Based First-line Regimen

Abstract: Minority resistant variants had no impact on the VR of treatment-naive patients to a rilpivirine-based regimen.

Cited by 17 publications

References 27 publications

First evaluation of the Next-Generation Sequencing platform for the detection of HIV-1 drug resistance mutations in Belgium

First evaluation of the Next-Generation Sequencing platform for the detection of HIV-1 drug resistance mutations in Belgium

Determining the Origins of Human Immunodeficiency Virus Type 1 Drug-resistant Minority Variants in People Who Are Recently Infected Using Phylogenetic Reconstruction

Analysis of unusual and signature APOBEC-mutations in HIV-1 pol next-generation sequences

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