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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 
* Corresponding author
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/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.
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Submitted on : Saturday, October 20, 2018 - 3:04:15 PM
Last modification on : Thursday, August 4, 2022 - 5:27:05 PM

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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, Oxford University Press (OUP), 2018, 66 (10), pp.1588 - 1594. ⟨10.1093/cid/cix1070⟩. ⟨hal-01899957⟩



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