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

N. Chantal Peltenburg, Jorgen Bierau, Jaap A. Bakker, Jolanda A. Schippers, Selwyn H. Lowe, Aimee D. C. Paulussen, Bianca J. C. van den Bosch, Mathie P. G. Leers, Bettina E. Hansen, Annelies Verbon*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Web of Science)

Abstract

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+21 A>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.
Original languageEnglish
Article numbere0191069
Number of pages14
JournalPLOS ONE
Volume13
Issue number1
DOIs
Publication statusPublished - 12 Jan 2018

Keywords

  • HUMAN-IMMUNODEFICIENCY-VIRUS
  • RIBAVIRIN-INDUCED ANEMIA
  • CHRONIC HEPATITIS-C
  • REVERSE-TRANSCRIPTASE
  • ITPA GENE
  • PYROPHOSPHOHYDROLASE DEFICIENCY
  • INFECTED PATIENTS
  • POLYMORPHISMS
  • INHIBITION
  • VARIANTS
  • Humans
  • Middle Aged
  • Male
  • HIV Infections/drug therapy
  • Young Adult
  • Anti-HIV Agents/administration & dosage
  • Erythrocytes/enzymology
  • Aged, 80 and over
  • Adult
  • Biomarkers/blood
  • Female
  • Pyrophosphatases/blood
  • Aged
  • Drug Therapy, Combination

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