People with HIV (PWH) are vulnerable to mental health and substance use disorders (MSDs), but the extent to which these are associated with other non-communicable diseases in ageing PWH populations remains poorly documented. We assessed comorbidities associated with symptoms of MSD among PWH ≥40 years in the Sentinel Research Network (SRN) of the International epidemiology Database to Evaluate AIDS (IeDEA). Baseline data collected between June 2020 and September 2022, from 10 HIV clinics in Asia, Latin America and Africa contributing to the SRN, were analysed. Symptoms of MSDs and comorbidities were assessed using standardized questionnaires, anthropometric and laboratory tests, including weight, height, blood pressure, glucose, lipids, chronic viral hepatitis and liver transient elastography. HIV viral load, CD4 count and additional routine clinical data were accessed from participant interview or medical records. HIV and non-HIV clinical associations of mental illness symptoms and unhealthy substance use were analysed using logistic regression. Mental illness symptoms were defined as moderate-to-severe depressive symptoms (PHQ-9 score >9), moderate-to-severe anxiety symptoms (GAD-7 >9) or probable post-traumatic stress disorder (PCL-5 >32). Unhealthy substance use was defined as ASSIST score >3, or AUDIT ≥7 for women (≥8 for men). Of 2614 participants assessed at baseline study visits, 57% were female, median age was 50 years, median CD4 was 548 cells/mm and 86% had HIV viral load 25 kg/m, 38% hypertension, 15% type 2 diabetes, 35% dyslipidaemia, 34% liver disease and 23% history of tuberculosis. BMI >25 and dyslipidaemia were found in 54% and 40% of those with mental illness symptoms compared to 49% and 34% of those without. Mental illness symptoms were not significantly associated with the clinical factors assessed. Unhealthy substance use was more likely among those with dyslipidaemia (OR 1.55, CI 1.16-2.09, p = 0.003), and less likely in those with BMI >25 (OR 0.48, CI 0.30-0.77, p = 0.009). Improved integration of MSD and comorbidity services in HIV clinical settings, and further research on the association between MSD and comorbidities, and care integration among older PWH in low-middle-income countries, are required.< Réduire