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Background CD4 lymphocyte cell count represents the main immunological marker used to monitor HIV infection. However, frequent monitoring may be unnecessary, could cause anxiety to the patient as well as burdening healthcare with extra expenses. Objectives and methods To analyse the probability of maintaining a safe number of CD4 in HIV-positive subjects under treatment with ≥350 cells/µl at baseline during a three-year follow up. We conducted a retrospective study performing three analyses with Kaplan-Meyer method considering: 1) all patients independently from their viral load (VL); 2) patients with 500 > CD4 ≥ 350 cells/µl versus (vs) CD4 ≥ 500 cells/µl at baseline; 3) patients with VL < 20 copies/ml vs VL > 20 copies/ml. Results 253 subjects were enrolled. The median CD4 count was 623 (489-805) cells/µl. Subjects maintaining ≥ 350 cells/µl in the first, second and third year were respectively 238 (94.1%), 229 (90.5%) and 226 (89.3%), independently from VL. Within subjects with ≥ 350 CD4/µl vs ≥ 500 CD4/µl at baseline, those who maintained ≥ 350 cells/µl until the third year were respectively 241 (95.3%) and 158 (98.1%). The probability of maintaining these values in the third year was 89.3% for those who had CD4 ≥ 350/µl at baseline and 98.1% for those who had CD4 ≥ 500/µl. This probability was around 90% vs 99% for subjects with HIV-RNA above or below 20 copies/ml. Secondly, we tried to estimate the costs of CD4 determinations in a three-year period (from April 1, 2013 to March 31, 2016). We analysed respectively 343 subjects in the first period, 364 in the second and 383 in the third, with a median value of 500 CD4/µl during the research time taken into account. We found a mean value of about two determinations patient/year (2.41 in 2013/2014; 2.32 in 2014/2015; 2.18 in 2015/2016), with a significant decrease between the first and the last period (p350 cells/µl) during a three-year follow up. It could be possible to save up to 66% of the costs by reducing the number of CD4 count determinations in a year, to have other favourable consequences as well, releasing new resources for patient’s management.