Autoimmune diseases can develop during HIV-1 infection, mainly related to the individual’s immune competence. The study investigated the association of theTREX1531C/T polymorphism and antinuclear antibodies (ANA) in HIV-1 infection and the time of antiretroviral therapy (ART) used. Cross-sectional and longitudinal assessments were carried out in 150 individuals, divided into three groups: ART-naïve, 5 years and 10 years on ART; ART-naïve individuals were evaluated for 2 years after initiation of treatment. The individuals’ blood samples were submitted to indirect immunofluorescence tests, real-time PCR and flow cytometry. TheTREX1531C/T polymorphism was associated with higher levels of TCD4+lymphocytes and IFN-α in individuals with HIV-1. Individuals on ART had a higher frequency of ANA, higher levels of T CD4+lymphocytes, a higher ratio of T CD4+/CD8+lymphocytes and higher levels of IFN-α than therapy-naïve individuals (p< 0.05). TheTREX1531C/T polymorphism was associated with better maintenance of the immune status of individuals with HIV-1 and ANA with immune restoration in individuals on ART, indicating the need to identify individuals at risk of developing an autoimmune disease.