Patient self-reported outcomes are increasingly important in measuring disease, treatment and care outcomes. It is unclear what constitutes well-being using a combined biomedical and psychosocial approach for patients with antiretroviral therapy (ART) access. This study aimed to determine the variance within the visual analogue scale (VAS) measure of health status using the existing five dimensions of the EuroQOL-5D, to identify which domains have the greatest effect on self-reported health status and to identify associations with the VAS using both biomedical and psychosocial factors among HIV outpatients. Consecutive patients in five UK clinics were recruited to a cross-sectional survey, n=778 (86% response rate). Patients self-completed validated measures, with treatment variables extracted from file. On the EuroQOL-5D, nearly one-third (28.1%) had mobility problems, one-fifth (18.7%) self-care problems, one-third (37.4%) difficulty in performing usual tasks and one-half (44.4%) reported pain/discomfort. In the regression model to determine associations with self-reported health status (VAS score), neither CD4 count nor ART status was associated with the outcome. However, in addition to four dimensions of the EuroQOL-5D, poorer health status was associated with worse physical symptom burden, treatment optimism and psychological symptoms. There is a relatively high prevalence of psychological morbidity and poor physical function, and these burdens of disease are associated with worse self-reported health status. As HIV management focuses on treatment for extended survival and a chronic model of disease, clinical attention to physical and psychological dimensions of patient care are essential to achieve optimal well-being.