Combination antiretroviral therapy has dramatically decreased AIDS-related mortality, allowing Persons Living with the Human Immunodeficiency Virus (PLWH) to live into advanced ages and, by virtue of older age, become at heightened risk for the same comorbidities experienced by healthy older adults. Data suggest that both increased age and HIV are independent risk factors for cognitive impairment and cognitive impairment directly affects Health-Related Quality of Life (HRQOL). This dissertation contributes to the science of caring for older PLWH. It explores the presence of cognitive function as measured by two tools. The Patient’s Assessment of Own Function Inventory (PAOFI) is a self-report measure of cognitive function and the Neuropsychological Test Battery (NTB) is a more time intensive clinical measure of cognitive function. This cross-sectional study was a secondary data analysis that determined if PAOFI is predictive of NTB performance and to determine cognitive and depressive symptom correlates to HRQOL in a cohort of PLWH age 60 and older. This sample included a total of 73 older PLWH in the San Francisco Bay Area. Self-report of cognitive function had no correlations with clinical measures of cognitive function in older PLWH. Depression explained more of the variance in PAOFI, controlling for the NTB. Older PLWH who reported better physical HRQOL also reported better cognitive function. Furthermore, those who reported better mental HRQOL scores reported less self-report of cognitive impairment, less depression, and scored better on the NTB. This study determined that self-report alone is not enough to detect cognitive impairment in older PLWH. Instead, the mental health summary score of the HRQOL was a better measure of cognitive function as assessed by the NTB. This work has broad implications for clinical care of older PLWH. A more comprehensive understanding of an older PLWH’s HRQOL has significant implications to improve the quality of care in older PLWH with cognitive impairment.