Adenosine Deaminase as a Biomarker of Tenofovir Mediated Inflammation in Naïve HIV Patients

• Published in: International journal of molecular sciences 2020-05, Vol.21 (10), p.3590
• Main Authors: Conesa-Buendía, Francisco Miguel, Llamas-Granda, Patricia, Atencio, Patricia, Cabello, Alfonso, Górgolas, Miguel, Largo, Raquel, Herrero-Beaumont, Gabriel, Mediero, Aránzazu
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; Adenosine; Adenosine deaminase; Adenosine Deaminase - blood; Adenosine Deaminase - metabolism; Adult; AIDS; Antiretroviral drugs; Antiretroviral therapy; biomarker; Biomarkers; Biomarkers - metabolism; CD4 antigen; Cytokines; Cytokines - metabolism; Granulocyte-macrophage colony-stimulating factor; HIV; HIV Infections - blood; HIV Infections - drug therapy; Human immunodeficiency virus; Humans; Inflammation; Inflammation - blood; Inflammation - pathology; Leukocytes (neutrophilic); Lymphocytes; Lymphocytes T; Male; Monocytes; Monocytes - metabolism; Neutrophils - metabolism; Nucleoside analogs; Plasma levels; Rheumatoid arthritis; Tenofovir; Tenofovir - pharmacology; Tenofovir - therapeutic use
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21103590

Plasma levels of adenosine deaminase (ADA), an enzyme that deaminates adenosine to inosine, are increased during inflammation. An increase in ADA activity occurs with lower human immunodeficiency virus (HIV) viral load and higher CD4 T cell counts. We aimed to investigate the role of plasma ADA as a biomarker of inflammation in treatment-naïve HIV patients who received tenofovir or another nucleoside analog for comparison. Ninety-two treatment-naïve patients were included in the study and grouped by treatment, i.e., tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF) or Triumeq. ADA activity was measured in plasma and cytokines were analyzed by MILLIPLEX MAP-Luminex Technology. Plasma concentration of monocytes and neutrophils was measured at 0, 3, and 12 months post-treatment. Treatment-naïve HIV patients had increased ADA concentrations (over 15 U/L) that decreased after treatment with TAF and Triumeq, though this did not occur in TDF-treated patients. However, all groups exhibited a pro-inflammatory systemic profile at 12 months of treatment. Plasma GM-CSF levels decreased after 12 months of treatment in the TDF group, with a concomitant decrease in blood monocyte count, and a negative correlation with ADA values was found. In conclusion, ADA levels may be modulated by antiretroviral therapy in HIV patients, possibly affecting inflammatory status.