Prevalence of Dolutegravir Resistance Among Adults Receiving Dolutegravir-based Antiretroviral Therapy with Virological Failure in Cuba

Background: In late 2018, Cuba incorporated Dolutegravir, a second-generation integrase inhibitor (INSTI), into its first-line antiretroviral treatment regimens. Monitoring HIV-1 drug resistance in patients with virological failure is critical for optimizing HIV care and treatment outcomes. This study assessed the prevalence of INSTI resistance among adults experiencing virological failure while receiving Dolutegravir-based ART in Cuba. Methods: Cross-sectional analysis using programmatic data from eight healthcare facilities, representing approximately 78% of adults receiving ART in Cuba. Adults (≥18 years) receiving all individuals receiving a Dolutegravir-based ART, who presented a confirmed virological failure (two consecutive viral loads >1000 copies/mL at least three months apart) between June 2022 and December 2024, were included. Demographic and clinical data were extracted from standardized laboratory requisition forms. Blood specimens were collected for HIV drug resistance and tested by Sanger sequencing, with resistance predicted using the Stanford HIVdb tool. Results: Among 110 eligible adults, 9 (8.2%) showed INSTI resistance-associated mutations, but only 6 had high level of resistance to Dolutegravir. Acquired HIV-1 drug resistance of any type was identified in 50.0% of patients (95% CI, 40·3–59·7). Additionally, 28.2% (95% CI, 20.6–37.2) carried mutations associated with resistance to non-nucleoside reverse transcriptase inhibitors and 18·2% (95% CI, 11.5-26.7) to nucleoside reverse transcriptase inhibitors. Two patients (1.8%) were found to have multidrug-resistant virus. Conclusions: The low prevalence of Dolutegravir resistance among patients with virological failure suggests that poor adherence, rather than antiviral resistance, may be the primary contributor to unsuppressed viral load in this population. These findings underscore the need to strengthen adherence support, alongside continued surveillance to promptly detect emerging resistance.