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

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.

• Authors: Stéphanie Raymond, Florence Nicot, Coralie Pallier, Pantxika Bellecave, Anne Maillard, Mary Anne Trabaud, Laurence Morand-Joubert, Audrey Rodallec, Corinne Amiel, Thomas Mourez, Laurence Bocket, Agnès Beby-Defaux, Magali Bouvier-Alias, Sidonie Lambert-Niclot, Charlotte Charpentier, Brice Malve, Audrey Mirand, Julia Dina, Hélène Le Guillou-Guillemette, Stéphanie Marque-Juillet, Anne Signori-Schmuck, Francis Barin, Ali Si-Mohamed, Véronique Avettand Fenoel, Catherine Roussel, Vincent Calvez, Karine Saune, Anne Geneviève Marcelin, Christophe Rodriguez, Diane Descamps, Jacques Izopet, French National Agency for Research on AIDS and Viral Hepatitis (ANRS) AC11 Resistance Study Group
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 66 Issue 10 Pg. 1588-1594 (05 02 2018) ISSN: 1537-6591 [Electronic] United States
• PMID: 29244143 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Rilpivirine

Topics

• Adult
• Drug Resistance, Viral
• Female
• Genetic Variation
• HIV Infections (drug therapy, virology)
• HIV-1 (drug effects, genetics)
• Humans
• Male
• Mutation
• Rilpivirine (administration & dosage, therapeutic use)
• Viral Load