Frequency of genotypic factors possibly associated with cabotegravir/rilpivirine failure in antiretroviral treatment-naïve and -experienced HIV-1- infected population

Objectives: The long-acting injectable (LAI) cabotegravir (CAB) and rilpivirine (RPV) treatment offers important advantages over oral ART (antiretroviral therapy), however baseline factors possibly contributing to the CAB/RPV treatment failure were identified. The purpose of this study was to describe the frequency of virologic factors previously influencing efficacy of this treatment, namely RPV and CAB resistance-associated mutations (RAMs) and A1/A6 subtype among naïve and treatment-experienced HIV-1-infected patients from Poland.

Methods: The following datasets of HIV-1 sequences were analysed: 4809 protease and reverse transcriptase (PR/RT) sequences obtained from 4649 Polish Caucasian patients (4122 naive and 687 non-naïve) supplemented with integrase (PR/RT/INT) sequences in 1217 cases (942 naïve and 275 non-naïve). Sub-subtypes A were assigned by phylogenetic methods. Major and minor CAB and RPV RAMs were determined according to the IAS-USA 2019 list, while minor RAMs were additionally defined based on the Stanford database algorithm.

Results: Subtype A1/A6 frequency ranged from 6.11% in ART failing cases with PR/RT sequences only, to 15.92% for the PR/RT/INT treatment-naïve dataset, while RPV RAMs were found in up to 5.89% of treatment-naïve and 14.56% of ART failing cases. Regardless treatment history, only <1% sequences had combination of two factors (RPV RAMs and A1/A6 subtype). Furthermore, CAB RAMs were found in 1.27% of treatment-naïve and 14.54% of experienced patients.

Conclusions: Despite notable frequency of subtype A1/A6 or CAB/RPV RAMs analysed separately, combination of at least two factors previously associated with failure or this treatment is rare. As subtype A1/A6 becomes more common across real-life cohorts continued subtyping and RAM screening will remain of key importance for LAI treatment implementation. Sequence data from this article have been deposited in GenBank under accession numbers: GU906860, GU906864, GU906871-GU906874, JQ305750-JQ305791, KC409134-KC409222, KM057341-KM057362, KM283892-KM284490, KT340108-KT340205, MZ468643-MZ468894, MZ671788-MZ671823, OP298017-OP302727.