The CHARTER study, a cross-sectional observational study, aimed to determine the frequency and associated features of HIV-associated neurocognitive disorders (HAND) in a large, diverse sample of HIV-infected individuals receiving combination antiretroviral therapy (CART). The study included 1,555 HIV-infected adults from six university clinics across the United States. Standardized neuromedical, psychiatric, and neuropsychological examinations were conducted, and participants were classified using the Frascati criteria for HAND. Results showed that 52% of the total sample had neuropsychological impairment, with higher rates in groups with greater comorbidity burden. Prevalence estimates for specific HAND diagnoses were 33% for asymptomatic neurocognitive impairment, 12% for mild neurocognitive disorder, and only 2% for HIV-associated dementia (HAD). Among participants with minimal comorbidities, a history of low nadir CD4 was a strong predictor of impairment, and the lowest impairment rate on CART occurred in those with suppressed plasma viral loads and nadir CD4 ≥200 cells/mm³. The study concluded that while HAD is rare, milder forms of HAND remain common even among those receiving CART and having minimal comorbidities. Future studies should explore whether early disease events trigger chronic CNS changes and whether early CART can prevent or reverse these changes.The CHARTER study, a cross-sectional observational study, aimed to determine the frequency and associated features of HIV-associated neurocognitive disorders (HAND) in a large, diverse sample of HIV-infected individuals receiving combination antiretroviral therapy (CART). The study included 1,555 HIV-infected adults from six university clinics across the United States. Standardized neuromedical, psychiatric, and neuropsychological examinations were conducted, and participants were classified using the Frascati criteria for HAND. Results showed that 52% of the total sample had neuropsychological impairment, with higher rates in groups with greater comorbidity burden. Prevalence estimates for specific HAND diagnoses were 33% for asymptomatic neurocognitive impairment, 12% for mild neurocognitive disorder, and only 2% for HIV-associated dementia (HAD). Among participants with minimal comorbidities, a history of low nadir CD4 was a strong predictor of impairment, and the lowest impairment rate on CART occurred in those with suppressed plasma viral loads and nadir CD4 ≥200 cells/mm³. The study concluded that while HAD is rare, milder forms of HAND remain common even among those receiving CART and having minimal comorbidities. Future studies should explore whether early disease events trigger chronic CNS changes and whether early CART can prevent or reverse these changes.