Impact of HIV-1 minority variants on the virus response to a rilpivirine-based first line regimen

Abstract

Background

Minority resistant variants of HIV-1 could influence the virological response to treatment based on non-nucleoside reverse transcriptase (RT) inhibitors. Data on minority rilpivirine-resistant variants are scarce. This study used next-generation sequencing (NGS) to identify patients harbouring minority resistant variants to nucleos(t)ide and non-nucleoside RT inhibitors and to assess their influence on the virological response (VR).

Methods

All the subjects, 541 HIV-1-infected patients being treated at 24 French virology laboratories, started their first line regimen containing rilpivirine between 2012 and 2015. VR was defined as a HIV-1 RNA virus load <50 copies/mL at month 6 with continued suppression at month 12. The RT gene was analysed by NGS at baseline (retrospectively) on the 454 GS-FLX platform (Roche).

Results

NGS revealed resistance-associated mutations (RAMs) accounting for 1-5% 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 (5.7%) patients who harbored rilpivirine-resistant variants with a 1% sensitivity threshold according to the ANRS 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 cell count <250 cells/µl at baseline, a slower decrease in virus 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 the treatment-naive patients to a rilpivirine-based regimen.