More Than Ever, Less Is More: Superior Effectiveness of Simplified Dual Art in Real-World Data From a Large Brazilian Cohort

Simplification of antiretroviral therapy (ART) to two-drug regimens aims to improve adherence and tolerability without compromising efficacy. This observational study, conducted in a reference center in Brazil, aimed to evaluate whether dual therapy is associated with better virological and immunological outcomes compared to triple-drug regimens. We included 1,020 people living with HIV (PLHIV), older than 18 years, on continuous ART between January 2020 and July 2022. Participants were allocated into two groups: simplified dual therapy (G2D, n = 379; 37.1%) and triple therapy (G3D, n = 641; 62.9%). Variables analyzed included age, sex, ART duration, CD4+ T-cell count, and HIV viral load (VL). Viral suppression was defined as VL < 50 copies/mL and virological failure as VL > 500 copies/mL. Multivariate logistic regression identified independent predictors of viral suppression, including age (≤ 50 vs. > 50 years), sex, ART duration (< 11 vs. ≥ 11 years), and regimen type. Frequencies were compared by chi-square test and means by Student’s or Mann-Whitney test (p < 0.05). Approved by the ethics committee. The proportion of male PLHIV was similar between G2D and G3D (∼66%; p = 0.432). Participants >50 years were more frequent in G2D (37.8% vs. 28.3%; p < 0.05). Viral suppression was higher in G2D (93.1% vs. 81.7%; p < 0.05), and virological failure was lower (1.6% vs. 10.1%; p < 0.05). CD4+ < 350 cells/mm³ occurred in 7.0% of G2D vs. 13.3% of G3D (p = 0.001). Dual therapy was an independent predictor of viral suppression (adjusted OR 2.57; 95% CI: 1.36–4.85; p = 0.0006), as was ART ≥ 11 years (adjusted OR 1.57; 95% CI: 1.02–2.42; p = 0.042). In real-world clinical practice, dual therapy showed higher viral suppression and better immune recovery, even after adjusting for age, sex, and ART duration. These findings support the feasibility of therapeutic simplification, offering reduced toxicity and complexity without loss of efficacy. Although this cohort suggests superiority of dual over triple therapy, prospective multicenter long-term studies are warranted to consolidate evidence on safety, effectiveness, and cost-effectiveness.