Prevalence of integrase strand transfer inhibitor (INSTI) resistance in people living with HIV and virological failure

Background: This study aims to delineate the resistance profiles of integrase strand transfer inhibitors (INSTIs) among patients in southern Taiwan who had experienced antiretroviral therapy (ART) failure. We focused on individuals previously treated with highly active ART (HAART) regimens, providing insights into the implications of INSTI resistance in a broader treatment-experienced population. Methods: Data were collected from patients failing an INSTI-containing regimen in a medical center in southern Taiwan between 2009 and 2022. Virological failure was defined as a plasma viral load >1000 copies/mL. Reverse transcriptase, protease, and integrase coding regions were sequenced at failure. Resistance-associated mutations included in the 2022 International Antiviral Society (IAS)-USA list were used. Drug resistance was analyzed using the HIV Stanford HIVDB 9.4 edition algorithm. Logistic regression analysis was used to analyze the risk factors associated with INSTI failure. Results: A total of 184 patients were enrolled for genotypic drug resistance testing due to virological failure, of whom 104 failed on nonnucleoside reverse transcriptase inhibitors, 58 on protease inhibitors (PIs), and 21 on INSTIs. Among 21 patients who failed INSTI therapy, 6 failed raltegravir-based treatment, 3 elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (EVG/COBI/FTC/TAF), 2 bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), and 10 abacavir/dolutegravir/lamivudine (ABC/DTG/3TC). Only 10 patients had INSTI drug resistance testing results available, and 40% (4/10) showed INSTI resistance at failure. Among the seven patients who failed on second-generation INSTIs with drug resistance reports available, one harbored E157Q and another with R263K mutations, respectively. Multivariable logistic regression analysis showed that patients with INSTI failure were less likely to have pol resistance ( p = 0.007, adjusted odds ratio [OR], 0.176, 95% CI, 0.050-0.618), less previous exposure to NNRTI ( p = 0.003, aOR, 0.063, 95% CI, 0.010-0.401), PIs ( p = 0.002, aOR, 0.030, 95% CI, 0.003-0.272), and with long duration of HAART ( p = 0.018, aOR, 1.02, 95% CI, 1.003-1.037). Conclusion: INSTI resistance was uncommon when used as the first-line single tablet regimen in Taiwan. The results confirmed the robustness of ABC/DTG/3TC and BIC/FTC/TAF regarding integrase resistance in cases of virological failure in routine clinical care.