AIMS: To assess associations of comorbidity patterns observed in people living with HIV (PLWH) with risk factors and health outcomes. METHODS: Common patters of comorbidities in PLWH participating in the POPPY study were determined using principal component analysis and a severity score for each pattern was derived. Associations between each pattern's severity score and risk factors were assessed using median regression. The independent associations of patterns' severity scores with self-reported physical and mental health (SF-36 summary scores) were assessed using linear regression, with functional impairment (Lawton IADL < 8) and hospitalization in last year using logistic regression and with number of general practitioner (GP) visits using Poisson regression. RESULTS: 1073 PLWH were analysed: 85.2% male, median (IQR) age 52 (47-59) years, 98% on therapy. Duration of HIV was associated with higher severity in 4/6 of patterns: cardiovascular diseases (CVD), mental health problems, metabolic disorders and chest/other infections (all p's≤0.001). Prior AIDS was associated with higher severity scores for the same patterns and for the pattern of cancers (p < 0.001). CVD was associated with poorer physical health (p = 0.02), higher risk of functional impairment (p = 0.02) and hospitalization (p < 0.001) and with higher number of GP visits (p < 0.001). Severity of mental health (all p's < 0.001) and of chest/other infections patterns negatively affected all the five health outcomes. CONCLUSION: Common patterns of comorbidities seen in PLWH appear to have different risk factors and to differently affect health outcomes. These findings may assist the development of targeted intervention to prevent, treat and manage the increasingly prevalent multimorbidity in PLWH.