{Reference Type}: Case Reports
{Title}: HIV-1 resistance against dolutegravir fluctuates rapidly alongside erratic treatment adherence: a case report.
{Author}: van Kampen JJA;Pham HT;Yoo S;Overmars RJ;Lungu C;Mahmud R;Schurink CAM;van Boheemen S;Gruters RA;Fraaij PLA;Burger DM;Voermans JJC;Rokx C;van de Vijver DAMC;Mesplède T;
{Journal}: J Glob Antimicrob Resist
{Volume}: 31
{Issue}: 0
{Year}: 12 2022
{Factor}: 4.349
{DOI}: 10.1016/j.jgar.2022.11.001
{Abstract}: 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.