Impact of Human Immunodeficiency Virus Type 1 Minority Variants on the Virus Response to a Rilpivirine-Based First-line Regimen
Authors: Raymond Stéphanie , Nicot Florence , Pallier Coralie , Bellecave Pantxika , Maillard Anne , Trabaud Mary Anne , Morand-Joubert Laurence , Rodallec Audrey , Amiel Corinne , Mourez Thomas , Bocket Laurence , Beby-Defaux Agnès , Bouvier-Alias Magali , Lambert-Niclot Sidonie , Charpentier Charlotte , Malve Brice , Mirand Audrey , Dina Julia , Le Guillou-Guillemette Hélène , Marque-Juillet Stéphanie , Signori-Schmuck Anne , Barin Francis , Si-Mohamed Ali , Avettand Fenoel Véronique , Roussel Catherine , Calvez Vincent , Saune Karine , Marcelin Anne Geneviève , Rodriguez Christophe , Descamps Diane , Izopet Jacques ,   French National Agency for Research on AIDS and Viral Hepatitis (ANRS) AC11 Resistance Study Group, 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 J C , Trabaud M A , 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 A G , Calvez V , Lambert-Niclot S , Soulié C , Wirden M , Morand-Joubert L , Delaugerre C , Chaix M L , Amiel C , Schneider V , Giraudeau G , Beby- Defaux A , Brodard V , Maillard A , Plantier J C , Chaplain C , Bourlet T , Fafi-Kremer S , Stoll-Keller F , Schmitt M P , Barth H , Yerly S , Poggi C , Izopet J , Raymond S , Barin F , Chaillon A , Marque-Juillet S , Roque-Afonso A M , Haïm-Boukobza S , Flandre P , Grudé M , Assoumou L , Costagliola D , Allegre T , Schmit J L , Chennebault J M , Bouchaud O , Magy-Bertrand N , Delfraissy J F , 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 J P , Katlama C , Simon A , Girard P M , Meynard J L , Molina J M , Pialoux G , Hoen B , Goeger-Sow M T , Lamaury I , Beaucaire G , Le Moal G , Jaussaud R , Rouger C , Michelet C , Borsa-Lebas F , Caron F , Khuong M A , Lucht F , Rey D , Calmy A , Lafeuillade A , Marchou B , Delobel P , Gras G , Greder-Belan A , Vittecoq D , Teiche E 
Published: December 2017

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 &lt;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 &lt;5% of variants in 17.2% of samples, for 5%–20% in 5.7% of samples, and for &gt;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 &lt;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.