CONTEXT: Twenty years after the advent of combined antiretroviral therapies (ARTs), there is a growing need for up-to-date information about the daily experience of people living with HIV (PLWH). OBJECTIVES: This study aimed to investigate the relationship between socioepidemiological groups and the types of bothersome symptoms reported by PLWH participating in a national survey in France. METHODS: We analyzed self-reported bothersome symptoms in a representative sample of PLWH (ANRS-VESPA2 survey), most of whom were receiving ART treatment. PLWH (N = 2505) were grouped into three clusters according to the number of bothersome symptoms reported: Cluster A (low number, n = 1848), Cluster B (moderate number, n = 271), and Cluster C (high number, n = 386). RESULTS: Individuals in Cluster A (low number of bothersome symptoms) were less likely to report all the symptom types investigated. Psychological, sexual, and general symptoms were more likely to be reported in Cluster B (moderate number), whereas gastric-, pain-, and appearance-related symptoms were more likely in Cluster C (high number). In multivariate analyses, women not natives of Sub-Saharan Africa and former/active female injecting drug users were more likely to report a medium or high number of symptoms, and lower adherence to ART. CONCLUSION: Combining new biomedical strategies with coping mechanisms and providing better support to socially vulnerable PLWH may improve this population's quality of health and daily life.