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

Stéphanie Raymond (1, 2) , Florence Nicot (3) , Coralie Pallier (4) , Pantxika Bellecave (5) , Anne Maillard (6) , Mary Anne Trabaud (7) , Laurence Morand-Joubert (8) , Audrey Rodallec (9) , Corinne Amiel (10) , Thomas Mourez (11) , Laurence Bocket (12) , Agnès Beby-Defaux (13) , Magali Bouvier-Alias (14) , Sidonie Lambert-Niclot (15) , Charlotte Charpentier (16, 17, 18) , Brice Malve (19) , Audrey Mirand (20) , Julia Dina (21) , Hélène Leguillou-Guillemette (22) , Stéphanie Marque-Juillet (23) , Anne Signori-Schmuck (24) , Francis Barin (25) , Ali Si-Mohamed (26) , Veronique Avettand-Fenoel (27) , Catherine Roussel (28) , Vincent Calvez (15) , Karine Saune (29, 2) , Anne Geneviève Marcelin (15) , Christophe Rodriguez (30) , Diane Descamps (16, 17, 31) , Jacques Izopet (29, 2)

1 CPTP - Centre de Physiopathologie Toulouse Purpan
2 UT3 - Université Toulouse III - Paul Sabatier
3 Laboratoire Virologie [CHU Toulouse]
4 Hôpital Paul Brousse
5 CHU Bordeaux
6 Laboratoire de Virologie [Rennes] = Virology [Rennes]
7 HCL - Hospices Civils de Lyon
8 CHU Saint-Antoine [AP-HP]
9 CHU Nantes - Centre Hospitalier Universitaire de Nantes
10 CHU Tenon [AP-HP]
11 Centre Hospitalier Universitaire de Rouen
12 CHU de Lille - Centre Hospitalier Universitaire de Lille
13 CHU de Poitiers - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
14 Hôpital Henri Mondor
15 CHU Pitié-Salpêtrière [AP-HP]
16 IAME (UMR_S_1137 / U1137) - Infection, Anti-microbiens, Modélisation, Evolution
17 INSERM UMR-S 606, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, PRES Sorbonne Paris-Cité, and Université Paris Denis Diderot,
18 Laboratoire de Virologie [AP-HP Hôpital Bichat-Claude-Bernard]
19 CHU Nancy - Centre Hospitalier Universitaire de Nancy
20 CHU Clermont-Ferrand
21 Service de Virologie [CHU Caen]
22 CHU Angers - Centre Hospitalier Universitaire d'Angers
23 CeRéMAIA - Hôpital André Mignot - Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses [CH Versailles]
24 CHU de Grenoble - Centre hospitalier universitaire de Grenoble
25 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
26 CHU Dijon - Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand
27 Hôpital Necker
28 Centre Hospitalier Universitaire d'Amiens
29 INSERM - Institut National de la Santé et de la Recherche Médicale
30 Service d'immunologie clinique et maladies infectieuses [Hôpitaux universitaires CHU Henri Mondor]
31 AP-HP - Hôpital Bichat - Claude Bernard [Paris]

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/mu L 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.

Mots clés: minority resistant variants; rilpivirine; first-line antiretroviral therapy; ultra-deep sequencing

Domaines: Maladies infectieuses; Virologie

Stéphanie Raymond, Florence Nicot, Coralie Pallier, Pantxika Bellecave, Anne Maillard, et al.. Impact of Human Immunodeficiency Virus Type 1 Minority Variants on the Virus Response to a Rilpivirine-Based First-line Regimen. Clinical Infectious Diseases, 2018, 66 (10), pp.1588 - 1594. ⟨10.1093/cid/cix1070⟩. ⟨hal-01899957⟩