ArticleJournal of global antimicrobial resistance2022
HIV-1 resistance against dolutegravir fluctuates rapidly alongside erratic treatment adherence: a case report.
Article in Journal of global antimicrobial resistance, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 8 citations in OpenAlex.
- Computational and Population-Based HLA Permissiveness to HIV Drug Resistance-Associated Mutations.Pathogens (Basel, Switzerland) · 2025Article
- Development and Optimization of Oligonucleotide Ligation Assay (OLA) Probes for Detection of HIV-1 Resistance to Dolutegravir.Viruses · 2024Article
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- The G118R plus R263K Combination of Integrase Mutations Associated with Dolutegravir-Based Treatment Failure Reduces HIV-1 Replicative Capacity and Integration.Antimicrobial agents and chemotherapy · 2023Article
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
objectivesWe report a case of incomplete HIV-1 suppression on a dolutegravir, lamivudine, and abacavir single-tablet regimen with the emergence of the H51Y and G118R integrase resistance mutations.
methodsIntegrase sequencing was performed retrospectively by Sanger and next-generation sequencing. Rates of emergence and decline of resistance mutations were calculated using next-generation sequencing data. Dolutegravir plasma concentrations were measured by ultra-performance liquid chromatography-tandem mass spectrometry. The effects of H51Y and G118R on infectivity, fitness, and susceptibility to dolutegravir were quantified using cell-based assays.
resultsDuring periods of non-adherence to treatment, mutations were retrospectively documented only by next-generation sequencing. Misdiagnosis by Sanger sequencing was caused by the rapid decline of mutant strains within the retroviral population. This observation was also true for a M184V lamivudine-resistant reverse transcriptase mutation found in association with integrase mutations on single HIV genomes. Resistance rebound upon treatment re-initiation was swift (>8000 copies per day). Next-generation sequencing indicated cumulative adherence to treatment. Compared to WT HIV-1, relative infectivity was 73%, 38%, and 43%; relative fitness was 100%, 35%, and 10% for H51Y, G118R, and H51Y+G118R viruses, respectively. H51Y did not change the susceptibility to dolutegravir, but G188R and H51Y+G118R conferred 7- and 28-fold resistance, respectively.
conclusionThis case illustrates how poorly-fit drug-resistant viruses wax and wane alongside erratic treatment adherence and are easily misdiagnosed by Sanger sequencing. We recommend next-generation sequencing to improve the clinical management of incomplete virological suppression with dolutegravir.
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