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Clin Infect Dis. 2018 May 2;66(10):1588-1594. doi: 10.1093/cid/cix1070.

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

Collaborators (144)

Lagier E, Roussel C, Le Guillou-Guillemette H, Alloui C, Bettinger D, Pallier C, Fleury H, Reigadas S, Bellecave P, Recordon-Pinson P, Payan C, Vallet S, Vabret A, Dina J, Henquell C, Mirand A, Bouvier-Alias M, de Rougemont A, Dos Santos G, Morand P, Signori-Schmuck A, Bocket L, Rogez S, Andre P, Tardy JC, Trabaud MA, Tamalet C, Delamare C, Montes B, Schvoerer E, Ferré V, André-Garnier E, Cottalorda J, Guinard J, Guiguon A, Descamps D, Brun-Vézinet F, Charpentier C, Visseaux B, Peytavin G, Krivine A, Si-Mohamed A, Avettand-Fenoel V, Marcelin AG, Calvez V, Lambert-Niclot S, Soulié C, Wirden M, Morand-Joubert L, Delaugerre C, Chaix ML, Amiel C, Schneider V, Giraudeau G, Beby-Defaux A, Brodard V, Maillard A, Plantier JC, 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, Allegre T, Schmit JL, Chennebault JM, Bouchaud O, Magy-Bertrand N, Delfraissy JF, Dupon M, Morlat P, Neau D, Ansart S, Jaffuel S, Verdon R, Jacomet C, Lévy Y, Dominguez S, Chavanet P, Piroth L, Cabié A, Leclercq P, Ajana F, Cheret A, Weinbreck P, Cotte L, Poizot-Martin I, Ravaud I, Christian B, Truchetet F, Grandidier M, Reynes J, May T, Goehringer F, Raffi F, Dellamonica P, Prazuck T, Hocqueloux L, Landman R, Yazdanpanah, Launay O, Weiss L, Viard JP, Katlama C, Simon A, Girard PM, Meynard JL, Molina JM, Pialoux G, Hoen B, Goeger-Sow MT, Lamaury I, Beaucaire G, Le Moal G, Jaussaud R, Rouger C, Michelet C, Borsa-Lebas F, Caron F, Khuong MA, Lucht F, Rey D, Calmy A, Lafeuillade A, Marchou B, Delobel P, Gras G, Greder-Belan A, Vittecoq D, Teiche E.

Author information

1
Institut national de la santé et de la recherche médicale (INSERM).
2
Université de Toulouse, Université Paul Sabatier, Physiopathology Center of Toulouse-Purpan.
3
Laboratoire de Virologie, Centre Hospitalier Universitaire (CHU) de Toulouse.
4
Laboratoire de Virologie, Hôpital Paul Brousse, Villejuif.
5
Laboratoire de Virologie, CHU de Bordeaux.
6
Laboratoire de Virologie, CHU de Rennes.
7
Laboratoire de Virologie, Hôpital de la Croix-Rousse, Hospices Civils de Lyon.
8
Laboratoire de Virologie, Hôpital Saint-Antoine, Paris.
9
Laboratoire de Virologie, CHU Hôtel-Dieu, Nantes.
10
Laboratoire de Virologie, Hôpital Tenon, Paris.
11
Laboratoire de Virologie, CHU de Rouen.
12
Laboratoire de Virologie, CHU de Lille.
13
Laboratoire de Virologie, CHU de Poitiers.
14
Laboratoire de Virologie, Hôpital Henri Mondor, Créteil.
15
Laboratoire de Virologie, Hôpital de la Pitié-Salpêtrière.
16
Infection, Antimicrobials, Modelling, Evolution, Unité Mixte de Recherche 1137, INSERM, Université Paris Diderot, Sorbonne Paris Cité, Assistance Publique-Hôpitaux de Paris.
17
Laboratoire de Virologie, Hôpital Bichat-Claude Bernard.
18
Laboratoire de Virologie, CHU de Nancy.
19
Laboratoire de Virologie, CHU de Clermont-Ferrand.
20
Laboratoire de Virologie, CHU de Caen.
21
Laboratoire de Virologie, CHU d'Angers.
22
Laboratoire de Virologie, Hôpital de Versailles, Le Chesnay.
23
Laboratoire de Virologie, CHU de Grenoble.
24
Laboratoire de Virologie, CHU de Tours.
25
Laboratoire de Virologie, CHU de Dijon.
26
Laboratoire de Virologie, Hôpital Necker, Paris.
27
Laboratoire de Virologie, CHU d'Amiens, France.

Abstract

Background:

Minority resistant variants of human immunodeficiency virus type 1 (HIV-1) could influence the virological response to treatment based on nonnucleoside reverse transcriptase inhibitors (NNRTIs). Data on minority rilpivirine-resistant variants are scarce. This study used next-generation sequencing (NGS) to identify patients harboring minority resistant variants to nucleos(t)ide reverse transcriptase inhibitors and NNRTIs and to assess their influence on the virological response (VR).

Methods:

All the subjects, 541 HIV-1-infected patients started a first-line regimen containing rilpivirine. VR was defined as a HIV-1 RNA load <50 copies/mL at month 6 with continued suppression at month 12. NGS was performed at baseline (retrospectively) on the 454 GS-FLX platform (Roche).

Results:

NGS revealed resistance-associated mutations accounting for 1% to <5% of variants in 17.2% of samples, for 5%-20% in 5.7% of samples, and for >20% in 29% of samples. We identified 43 (8.8%) and 36 (7.4%) patients who harbored rilpivirine-resistant variants with a 1% sensitivity threshold according to the French National Agency for Research on AIDS and Viral Hepatitis and Stanford algorithms, respectively. The VR was 96.9% at month 12. Detection of minority rilpivirine resistant variants was not associated with virological failure (VF). Multivariate analysis indicated that VF at month 12 was associated with a CD4 count <250 cells/µL at baseline, a slower decrease in viral load at month 3, and rilpivirine resistance at baseline using the Stanford algorithm with a 20% threshold.

Conclusions:

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

PMID:
29244143
DOI:
10.1093/cid/cix1070
[Indexed for MEDLINE]

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