Background: Modern antiretroviral therapy provides numerous effective and well-tolerated treatment options for individuals living with HIV. However, due to medication tolerability, toxicity, and cost optimization associated with the emergence of highly potent drugs, dual therapy has emerged as a new therapeutic alternative for patients with viral suppression. Observational studies worldwide are being conducted to assess the effectiveness of dual therapy in people living with HIV/AIDS. A real-world study is important to validate the findings obtained in controlled studies. Objective: Assess the effectiveness of dual therapy with lamivudine and dolutegravir compared to triple therapy in real-life settings. Methods: The study was conducted at São José Infectious Diseases Hospital, a tertiary referral hospital in the state of Ceará, northeast Brazil, for the treatment of PLWHA. Results: A total of 521 patients were taking double therapy with lamivudine plus dolutegravir and 450 patients were in triple therapy, mostly in the use of association with dolutegravir, were analyzed. Patients on dual therapy had a higher median age compared to those on triple therapy. A statistically significant higher viral suppression was observed in patients on dual therapy compared to triple therapy (p < 0,001). Viral suppression on dual therapy under 200 copies was 97.2%. There was a statistically significant higher percentage of patients with higher CD4/CD8 ratio using triple therapy compared to dual therapy. Conclusion: The current study suggests a higher effective response to dual therapy compared to triple therapy in PLWHA in the real-world, supporting therapy simplification as a sustainable option to maintain virological suppression in patients experiencing toxicity or comorbidities.