Background <p>People living with HIV (PLWH) aged ≥ 50 years face health challenges, including HIV-associated mild neurocognitive disorder. Cognitive reserve is a crucial neuroprotective mechanism that may help this population benefit from interventions designed to enhance cognitive function. However, the factors influencing cognitive reserve development in this group remain underexplored.</p> Objective <p>This study aimed to identify facilitators and barriers to enhancing cognitive reserve in individuals aged ≥ 50 with HIV-associated mild neurocognitive disorder, to inform the development of personalized interventions.</p> Methods <p>Purposive sampling was used to recruit participants from Luzhou, Sichuan. Semi-structured interviews were conducted with 26 PLWH aged ≥ 50 experiencing mild cognitive issues, including 19 men and seven women, with a mean age of 61.1 years. Interviews were recorded, transcribed, and analyzed using NVivo 14 and traditional content analysis.</p> Results <p>Qualitative analysis identified two primary themes, comprising 12 sub-themes, related to facilitators and barriers to improving cognitive reserve. Key facilitators included perceived cognitive symptoms, compensatory strategies, individualized needs, valued self-efficacy, and external monitoring. Significant barriers included negative perceptions of health status, limited risk perception, concerns about privacy breaches, knowledge deficits, physical limitations, competing priorities, and financial cost.</p> Conclusion <p>This study highlights key factors influencing cognitive reserve enhancement in PLWH aged ≥ 50 years, emphasizing the need for tailored interventions to address barriers and leverage facilitators. These findings provide a foundation for targeted programs to improve cognitive function in this population.</p>