%0 Case Reports
%T HIV-1 resistance against dolutegravir fluctuates rapidly alongside erratic treatment adherence: a case report.
%A van Kampen JJA
%A Pham HT
%A Yoo S
%A Overmars RJ
%A Lungu C
%A Mahmud R
%A Schurink CAM
%A van Boheemen S
%A Gruters RA
%A Fraaij PLA
%A Burger DM
%A Voermans JJC
%A Rokx C
%A van de Vijver DAMC
%A Mesplède T
%J J Glob Antimicrob Resist
%V 31
%N 0
%D 12 2022
%M 36347497
%F 4.349
%R 10.1016/j.jgar.2022.11.001
%X We 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.<BR>Integrase 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.<BR>During 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.<BR>This 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.