‘Leaving no stones unturned’: up to 10 years results on the effectiveness, tolerability and metabolic safety of dolutegravir+lamivudine (DTG+3TC) as a switch regimen in the ODOACRE cohort

Background: Dolutegravir plus lamivudine (DTG+3TC) is widely used as a two-drug switch regimen for virologically suppressed PWH. We report long-term real-world data on effectiveness, tolerability, immunological recovery and metabolic/cardiovascular outcomes in a large, multicentre Italian cohort. Methods: We performed a retrospective observational analysis of participants in the ODOACRE cohort who switched to DTG+3TC between January 2015 and January 2025 across eight Italian centres. Inclusion criteria were age ≥18, HIV-RNA <50 copies/mL for ≥6 months at switch, HBsAg negative. Primary outcomes were time to virological failure (VF) and time to treatment discontinuation (TD) for any cause. Kaplan-Meier survival analysis and Cox regression models were used to evaluate predictors. Changes in metabolic and immunological markers were assessed using linear mixed models and linear regression. Results: A total of 2535 participants were included. Estimated probabilities of maintaining virological suppression were 99.5% at 48 weeks, 96.1% at 240 weeks and 90.4% at 480 weeks. In multivariate analysis, longer time since HIV diagnosis (per year aHR 1.038) and zenith HIV-RNA >500 000 copies/mL (aHR 2.205) predicted VF, whereas longer prior virological suppression was protective (per year aHR 0.869). During 9721.6 PYFU we observed 362 TDs (3.72 per 100 PYFU), with probabilities of regimen maintenance of 94.4%, 83.5% and 78.7% at weeks 48, 240 and 480, respectively. Conclusions: In our real-world cohort with extended follow-up, DTG+3TC as a switch regimen was associated with durable virological suppression and favourable tolerability. Metabolic findings should be considered descriptive and exploratory, within the limits of an observational, uncontrolled study.