This study compared the prevalence and risk factors for noninfectious comorbidities (NICMs) among HIV-infected adults with those in a matched general population. The research involved a case-control study of 2854 HIV-infected patients and 8562 control subjects from the CINECA ARNO database. NICMs included cardiovascular disease, hypertension, diabetes mellitus, bone fractures, and renal failure. Polypathology (Pp), defined as the presence of ≥2 NICMs, was also assessed. The results showed that the prevalence of individual NICMs and Pp was significantly higher among HIV-infected patients compared to controls across all age strata. Pp prevalence among patients aged 41-50 years was similar to that among controls aged 51-60 years. Independent predictors of Pp in the overall cohort included age, male sex, nadir CD4 cell count <200 cells/μL, and exposure to antiretroviral therapy (ART). The findings suggest that HIV-infected patients have a higher prevalence of age-related NICMs and Pp compared to the general population, with the onset of these conditions occurring earlier. This highlights the need for earlier screening and preemptive interventions to prevent common age-related NICMs in HIV-infected individuals.This study compared the prevalence and risk factors for noninfectious comorbidities (NICMs) among HIV-infected adults with those in a matched general population. The research involved a case-control study of 2854 HIV-infected patients and 8562 control subjects from the CINECA ARNO database. NICMs included cardiovascular disease, hypertension, diabetes mellitus, bone fractures, and renal failure. Polypathology (Pp), defined as the presence of ≥2 NICMs, was also assessed. The results showed that the prevalence of individual NICMs and Pp was significantly higher among HIV-infected patients compared to controls across all age strata. Pp prevalence among patients aged 41-50 years was similar to that among controls aged 51-60 years. Independent predictors of Pp in the overall cohort included age, male sex, nadir CD4 cell count <200 cells/μL, and exposure to antiretroviral therapy (ART). The findings suggest that HIV-infected patients have a higher prevalence of age-related NICMs and Pp compared to the general population, with the onset of these conditions occurring earlier. This highlights the need for earlier screening and preemptive interventions to prevent common age-related NICMs in HIV-infected individuals.