Disfunção imune em indivíduos HIV positivos sob terapia antirretroviral: papel da razão CD4/CD8 e da atividade da enzima adenosina desaminase

Abstract

Human immunodeficiency virus (HIV) uncontrolled replication results in the Acquired Immunodeficiency Syndrome (AIDS). Antiretroviral therapy (ART) reduces morbidity and mortality but inflammation and immune activation remain. Two parameters are assessed in this thesis in HIV-positive individuals under ART and on viral suppression: the CD4/CD8 ratio and the activity of adenosine deaminase (ADA). CD4/CD8 and its relationships with comorbidities and aging were evaluated in a retrospective study with clinical and laboratory data from 352 HIV-positive individuals under ART. Despite the high prevalence of CD4/CD8 <1 (68%) and comorbidities (62%), no association was observed between them. The prevalence of comorbidities increased with aging, while the decrease in CD4/CD8 was associated only with neurocognitive diseases. ADA was investigated by studying the activity of ADA in serum and ecto-ADA in peripheral blood mononuclear cells (PBMCs) of 47 HIV-positive individuals and 71 controls, as well as serum parameters of oxidative stress. Compared to the control group, the HIV group showed increased serum ADA activity and reactive oxygen species (EROS) levels, and a reduction of E-ADA activity in PBMCs. The increase in serum ADA activity in the HIV group was associated with CD4/CD8<1 (66%) and elevated EROS levels, while the decrease in E-ADA in PBMCs was associated with the decrease in the CD4/CD8 ratio. A high prevalence of CD4/CD8<1 was observed in both studies and the activities of ADA were associated with changes in the CD4/CD8 ratio. Both markers indicate the permanence of immune dysfunction, regardless of the duration of treatment and the duration of viral suppression.