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Background Maintaining good adherence to combined antiretroviral therapy is essential for retaining virologic success. Low adherence is a common condition in clinical practice, and one possible way to deal with this issue is to switch poorly adherent individuals to triple regimens with a high genetic barrier and a favourable forgiveness profile to reduce failure. The present study aimed to describe the rate of virologic success when people with HIV (PWH) who are poorly adherent are switched from 2DR to 3DR.Methods This retrospective, monocentric study enrolled all individuals with low adherence, defined as at least two detectable viral loads in the previous 18 months, from 2018 to 2025. Participants were stratified according to the treatment decided by the physicians in (i) remaining in 3DR (control group); (ii) remaining in 2DR; and (iii) switching to 3DR regimens with high genetic barrier and forgiveness. Descriptive and nonparametric statistics were used to describe study population, while bivariate logistic regression analysis was used to assess the effect of the regimen on the achievement of virologic control, defined as >90% of the follow-up time spent with an undetectable viral load. Standard survival analyses were used to estimate the risk of virologic failure (i.e., two consecutive values >200 cp/mL or one value >1,000 co/mL).Results Of the 2,485 PWH who attended our clinic during the study period, 548 presented with poor adherence (22.1%). They were mainly men (77.7%), with a median age of 50 (IQR 42-58) years, and GBMSM (42.5%); however, the proportions of IVDU and foreign-born PWH were relevant (17.9% and 33.6%, respectively). The majority remained with their ongoing regimens (3DR in 53.4% and 2DR in 34.1%); only 13.5% switched to a 3DR with a high genetic barrier and forgiveness (BIC-based in 59.5% of cases, mostly IVDUs and foreign-born, and with a higher baseline viral load). The rate of PWH who remained for >90% of the time with an undetectable viral load was higher with 2DR (32.6 %) than with switching (23.0%) or remaining in 3DR (22.7%) at the limit of statistical significance. After adjusting for age, risk of exposure, Italian birth, and baseline viral load, switching was not associated with an increased odds of achieving virologic success (aOR 0.32, 95%CI 0.48-1.67). We registered 66 virologic failures (12.0%; figure 1). Adjusted Cox regression analysis did not find a protective effect when switching (aHR 1.20, 95%CI 0.61-2.36).Discussion Poor adherence is a common condition affecting frequently IVDUs and foreign-born PWH. Switching from 2DR to 3DR with high genetic barrier and forgiveness did not lead to increased virologic success and reduced virologic failure. These results should be interpreted cautiously because the individuals who switched were characterised by more detrimental conditions that could not be compensated by the treatment change alone.Abstract OC52 Figure 1Kaplan-Meier estimate for virologic failure according to treatment group