Tese
Disfunção imune em indivíduos HIV positivos sob terapia antirretroviral: papel da razão CD4/CD8 e da atividade da enzima adenosina desaminase
Date
2021-03-31Author
Passos, Daniela Ferreira
Institutions
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.