Background: Prior research has documented associations between treatment optimism related to highly active anti-retroviral therapy (HAART) and lower levels of protective behavior. The majority of these studies were conducted in higher income countries and with men who have sex with men (MSM). Researchers now recognize the impartance of examining the existence and nature of optimism in lower income countries and with other populations. This stady sought to investigate local beliefs and behaviors related to HAART among heterosexuals, injection drug users (IDU), and MSM in Rio de Janeiro, Brazil. Methods: 80 semi-structured in-depth interviews were conducted with 40 heterosexuals, 20 IDU and 10 MSM recruited from 3 pubtic health facilities catering to low-income groups. Half of ‘participants were HIV+. Selection criteria included HIV+ participants receiving HAART and HIV- participants seeking STI services. Topics explored included: HAART-related Imowledge, attitudes, and experiences; relationship whealth ‘providers; family and social support; historic/current HIV protective behavior. Results: Some participants acknowledged the existence of HAART optimism and associated risk behavior. However, the construction of optimism in this setting is distinct from prior conceptions where optimism measures have focused on how perceptions of lower viral loads lead people to perceive themselves or others as less infectious. Our findings suggest that many participants had very little knowledge of their treatment regimens and very few could define viral load. According to participants, optimism was more likely related to people feeling better and no longer looking sick than technical associations between viral load and perceived risk. Conclusions: The nature of treatment optimism is distinct across populations and contexts. Measures and interventions related to HAART and HIV prevention should be adapted to fit local knowledge and beliefs.