Objectives: To assess the effect of protease inhibitor (PI)-based dual therapy on CD4/CD8 ratio during the first year of therapy in antiretroviral therapy (ART)-naïve patients using data from randomized controlled clinical trials. Methods: We pooled data from the GARDEL and ANDES studies, both randomized controlled clinical trials that recruited ART-naïve people living with HIV and randomly assigned them to receive PI-based dual therapy (DT) or triple therapy (TT) aiming to compare viral efficacy. We compared median CD4/CD8 ratios and the proportion of patients with CD4/CD8 ratio > 1 at 48 weeks after ART initiation in both treatment arms using the Mann–Whitney U-test and the χ2 test. We performed subgroup analysis for patients > 50 years old, with baseline CD4 counts ≤ 200 cells/μL, viral load > 100 000 HIV RNA copies/mL, and ritonavir-boosted lopinavir-based therapy. Results: We analysed data from 571 patients: 292 on DT and 279 on TT. No differences were observed in CD4/CD8 ratio (0.632 vs. 0.617, P = 0.729) or in the proportion of patients with CD4/CD8 ratio > 1 (17.9% vs. 19.3%, P = 0.678) 48 weeks after ART initiation. Subgroup analysis showed no further differences. Conclusion: The impact of PI-based DT regimens on the CD4/CD8 ratio during the first year of treatment for ART-naïve patients is similar to that of TT.