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Poor health literacy is a prevalent barrier to medical care and people with lower health literacy experience greater illness severity than people with higher health literacy. Health literacy may therefore be an important factor in the health and treatment of people living with HIV-AIDS.A community-recruited sample of 339 HIV-infected men and women completed surveys and interviews that assessed functional health literacy, health status, AIDS-related disease and treatment knowledge, and health care perceptions and experiences. Medical records were available for chart abstraction of health status for a subsample of participants.About 1 of 4 people living with HIV-AIDS demonstrated difficulty comprehending simple medical instructions and therefore lower health literacy. HIVinfected people with lower health literacy had lower CD4 cell counts, higher viral loads, were less likely to be taking antiretroviral medications, reported a greater number of hospitalizations, and reported poorer health than those with higher health literacy. In addition, after adjusting for years of formal education, lower health literacy was associated with poorer knowledge of one's HIV-related health status, poorer AIDS-related disease and treatment knowledge, and more negative health care perceptions and experiences.Health literacy is a significant factor in the health and treatment of persons living with HIV-AIDS. Interventions are needed to improve medical care and the health status of people with lower health literacy that are living with HIV-AIDS.