Low prevalence of resistance mutations to integrase inhibitors (INI) in patients living with HIV-1 at baseline using next generation sequencing (NGS)

Current guidelines indicate that baseline INI resistance testing is not required; however, increased prescribing may lead to increased resistance mutation prevalence. NGS allows the detection of minority variants (MVs) not be detected by conventional methods. Barts Health NHS Trust patient records were reviewed to identify INI naïve patients prescribed INI between March 2014 and March 2017. Baseline plasma samples were extracted for nucleic acid and amplified in a single RT-PCR. Libraries were prepared using the Nextera XT library preparation kit and sequencing performed on an Illumina Miseq. Sequencing reads were assembled into consensus sequences and resistances determined using the Stanford HIV resistance database (HIVdb). MVs were variants <20 % of the overall population. Of 248 patients prescribed INI, 128 patients were excluded from the study due to an undetectable viral load or lack of sample. Of the remaining 121 patients, integrase sequences were successfully obtained from 91. No major INI mutations were detected. Six patients were identified with an HIVdb INI score ≥10: E157Q (4 patients) and T97A (2 patients). Only 1 MV accessory mutations was observed (A128T). Of patients with resistance mutations, 5 received raltegravir- and 2 received dolutegravir-based regimes. No treatment failures were observed. Prevalence of baseline INI mutations increased in recent years: 0/12 (0 %) patients in 2014–2015, 2/32 (6.3 %) patients in 2015–2016 and 5/47 (10.6 %) patients in 2016–2017. Resistance MVs to INI were extremely rare. Although this study supports current baseline INI resistance testing guidelines, increasing mutation prevalence’s may require future revision of guidelines.