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The main objective of the work was to evaluate the use of CD38 on T lymphocytes, IFNγ (+874 A/T), and IL-10 (−1082 A/G) polymorphisms in HIV-infected patients under antiretroviral (ARV) therapy. Sixty-one patients were selected at the outpatient clinic for HIV infection at the Hospital São José de Doenças Infecciosas, Fortaleza, Ceará, Brazil. The patients were classified into two groups, according to viral load after one year of ARV therapy. In the aviremic group (group I), a reduction of 35.5% of CD38+CD4+ T cells was observed (p = 0.02) and 49.3% of CD38+CD8+ T cells (p = 0.001). In the viremic group (group II), a reduction of 37.2% of CD38+CD4+ T cells (p = 0.067), and 21.4% of CD38+CD8+ T cells (p = 0.60) occurred. No association was found between IL-10 (−1082) polymorphism and the type of response to ARV therapy. Regarding the gene polymorphism on IFNγ (+874 T/A), 73.34% of group I and 33.3% of group II presented the AA genotype. The relative risk of the individuals carrying AA genotype or the A allele and not being able to suppress the viral load level after one year of ARV therapy was 3.44 (1.25-9.45; p = 0.014) or 2.35 (1.05-5.26; p = 0.027), respectively. Our data suggested that an augmented frequency of activated CD38+CD8+ T cells as well as the presence of the A allele of IFNγ polymorphism could contribute to a reduced virological suppression in patients under antiretroviral therapy.