Erythrocyte Inosine triphosphatase activity: A potential biomarker for adverse events during combination antiretroviral therapy for HIV

• Published in: PloS one Vol. 13; no. 1; p. e0191069
• Main Authors: Peltenburg, N Chantal, Bierau, Jörgen, Bakker, Jaap A, Schippers, Jolanda A, Lowe, Selwyn H, Paulussen, Aimée D C, van den Bosch, Bianca J C, Leers, Mathie P G, Hansen, Bettina E, Verbon, Annelies
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12-01-2018; Public Library of Science (PLoS)
• Subjects: Abacavir; Adult; Aged; Aged, 80 and over; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - therapeutic use; Antiretroviral drugs; Biological markers; Biology and Life Sciences; Biomarkers - blood; Care and treatment; Complications and side effects; Dosage and administration; Drug Therapy, Combination; Erythrocytes - enzymology; Female; Genotypes; Health aspects; Highly active antiretroviral therapy; HIV; HIV Infections - drug therapy; Human immunodeficiency virus; Humans; Infection; Inosine Triphosphatase; Male; Medicine and Health Sciences; Middle Aged; Physical Sciences; Pyrophosphatases - blood; Regression analysis; Research and Analysis Methods; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0191069

The purine analogues tenofovir and abacavir are precursors of potential substrates for the enzyme Inosine 5'-triphosphate pyrophosphohydrolase (ITPase). Here, we investigated the association of ITPase activity and ITPA genotype with the occurrence of adverse events (AEs) during combination antiretroviral therapy (cART) for human immunodeficiency virus (HIV) infection. In 393 adult HIV-seropositive patients, AEs were defined as events that led to stop of cART regimen. ITPase activity ≥4 mmol IMP/mmol Hb/hour was considered as normal. ITPA genotype was determined by testing two ITPA polymorphisms: c.94C>A (p.Pro32Thr, rs1127354) and c.124+21A>C (rs7270101). Logistic regression analysis determined odds ratios for developing AEs. In tenofovir-containing regimens decreased ITPase activity was associated with less AEs (p = 0.01) and longer regimen duration (p = 0.001). In contrast, in abacavir-containing regimens decreased ITPase activity was associated with more AEs (crude p = 0.02) and increased switching of medication due to AEs (p = 0.03). ITPA genotype wt/wt was significantly associated with an increase in the occurrence of AEs in tenofovir-containing regimens. Decreased ITPase activity seems to be protective against occurrence of AEs in tenofovir-containing cART, while it is associated with an increase in AEs in abacavir-containing regimens.