The efficacy and safety of HAART regimens based on fixed-dose combination zidovudine/lamivudine (ZDV/3TC) or abacavir/lamivudine (ABC/3TC) have been well studied over the years. Although ZDV is not recommended as first-choice regimen in current guidelines, several patients are still on a ZDV-based regimen. The aim of this retrospective observational study was to evaluate the presence of significant improvements and/or possible side effects after switching from ZDV to ABC in 19 patients with HIV infection on HAART, who switched from a ZDV based regimen to ABC/3TC, at the Outpatient Clinic of Infectious Diseases of the Garibaldi Nesima Hospital, Catania. 13 patients (68%) switched for simplification, 6 (32%) for toxicity. We found no statistically significant changes in HIV viral load, CD4+ count, CD8+ count and CD4/CD8 ratio, hemoglobin levels, creatinine, glucose, GPT, total cholesterol and triglycerides. We found a significant increase in red (p=0.0001) and white (p=0.002) blood cell count and a significant decrease in MCV (p=0.003) and platelet count (p=0.012). This study shows that switching from ZDV to ABC is safe and results in an improvement of MCV, red and white blood cell count. The decrease in platelet count should be confirmed and further analyzed.