Approximately two-thirds of Romanian HIV patients were parenterally infected with the F subtype of HIV in early childhood. They are now in the context of immunological aging, with immunosuppression posing an additional challenge in developing the most effective and well-tolerated regimens. The risk of an improper immune recovery is higher in these patients than in newly diagnosed patients. The primary goal of this retrospective study was to conduct a comparative analysis of the immune recovery, measured at three time points, on 462 HIV-infected patients who were registered at the “Matei Balş National Institute of Infectious Diseases”, Bucharest, Romania, between 2018 and 2021, as follows: darunavir (DRV) 600 mg plus ritonavir (RTV) 100 mg (twice daily) was given to 384 patients, while DRV 800 mg plus cobicistat (COBI) 150 mg was given to 78 patients (once daily). The immune response was assessed by counting T lymphocytes, CD4 count cells/mm³, and the CD4/CD8 lymphocyte count ratio. Additionally, the study assessed the relationship between the immune and virological responses to therapy. Using various statistical tests, the results revealed that the immune response is normal in both groups, but with a statistically significant difference (p < 0.05) for the DRV/c group. Statistical associations between RNA viral plasma load and immune response (CD4 count and CD4/CD8 ratio) were assessed at all three visits and showed an insignificant association for the first two time points; however, at the final visit, the outcomes changed and reached statistical significance for both groups.