Surveillance of HIV-1 transmitted integrase strand transfer inhibitor resistance in the UK

Background: HIV treatment guidelines have traditionallly recommended that all HIV-positive individuals are tested for evidence of drug resistance prior to starting ART. Testing for resistance to reverse transcriptase inhibitors and PIs is well established in routine care. However, testing for integrase strand transfer inhibitor (InSTI) resistance is Less consistent. Objectives: To inform treatment guidelines by determining the prevalence of InSTI resistance in a national cohort of recenly infected individuals. Patients and methods: Recent (within 4 months) HIV-1 infections were identified using a Recent Infection Testing Algorithm of new HIV-1 diagnoses in the UK. Resistance-associated mutations (RAMs) in integrase, protease and reverse transcriptase were detected by ultradeep sequencing, which allows for the sensitive estimation of the frequency of each resistant variant in a sample. Results: The analysis included 655 randomly selected individuals (median age= 33 years, 95% male, 83% MSM, 78% white) sampled in the period 2014 to 2016 and determined to have a recent infection. These comprised 320, 138 and 197 samples from 2014, 2015 and 2016, respectively. None of the samples had major InSTI RAMs occurring at high variant frequency (>= 20%). A subset (25/640, 3.9%) had major InSTI RAMs occurring onLy as Low-frequency variants (2%-20%). In contrast, 47/588 (8.0%) had major reverse transcriptase inhibitor and PI RAMs at high frequency. Conclusions: Between 2014 and 2016, major InSTI RAMs were uncommon in adults with recent HIV-1 infection, only occurring as low-frequency variants of doubtful clinical significance. Continued surveilance of newly diagnosed patients for evidence of transmitted InSTI resistance is recommended to inform clinical practice.