PURPOSE: Health literacy is lower in minorities and older adults, and has been associated with nonadherence to medications, treatment, and care in people living with human immunodeficiency virus (HIV). Likewise, African Americans with HIV are more likely to be nonadherent to their HIV medications, less likely to keep their clinic appointments related to HIV treatment and care, and more likely to die during hospitalizations than their ethnic counterparts. The present study explored the preferences of older African Americans with HIV for a health literacy intervention to promote HIV management. PATIENTS AND METHODS: In this qualitative study, 20 older adult African Americans living with HIV were recruited from an HIV/acquired immunodeficiency syndrome outpatient clinic in the southeastern region of the US. Using patient-centered participatory design methods, semi-structured individual interviews were conducted to determine patient preferences for intervention development and design. Health literacy was also measured using the Rapid Estimate of Adult Literacy in Medicine - Revised (REALM-R). RESULTS: Four major themes emerged related to intervention development and design: keep health information simple; use a team-based approach for health education; tailor teaching strategies to patients' individual needs; and account for patients' low experience, but high interest, in technology. Forty-five percent of the study population had low health literacy based on the revised Rapid Estimate of Adult Literacy in Medicine. CONCLUSION: Future interventions that target minorities and older adults living with HIV should consider patients' learning needs, sex-specific and mental health needs, and delivery approaches, in order to increase uptake and improve disease management and health outcomes.