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

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 antiretro...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5766130/
https://www.ncbi.nlm.nih.gov/pubmed/29329318
http://dx.doi.org/10.1371/journal.pone.0191069
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author 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
author_facet 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
author_sort Peltenburg, N. Chantal
collection PubMed
description 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.
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spelling pubmed-57661302018-01-23 Erythrocyte Inosine triphosphatase activity: A potential biomarker for adverse events during combination antiretroviral therapy for HIV 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 PLoS One Research Article 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. Public Library of Science 2018-01-12 /pmc/articles/PMC5766130/ /pubmed/29329318 http://dx.doi.org/10.1371/journal.pone.0191069 Text en © 2018 Peltenburg et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
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
Erythrocyte Inosine triphosphatase activity: A potential biomarker for adverse events during combination antiretroviral therapy for HIV
title Erythrocyte Inosine triphosphatase activity: A potential biomarker for adverse events during combination antiretroviral therapy for HIV
title_full Erythrocyte Inosine triphosphatase activity: A potential biomarker for adverse events during combination antiretroviral therapy for HIV
title_fullStr Erythrocyte Inosine triphosphatase activity: A potential biomarker for adverse events during combination antiretroviral therapy for HIV
title_full_unstemmed Erythrocyte Inosine triphosphatase activity: A potential biomarker for adverse events during combination antiretroviral therapy for HIV
title_short Erythrocyte Inosine triphosphatase activity: A potential biomarker for adverse events during combination antiretroviral therapy for HIV
title_sort erythrocyte inosine triphosphatase activity: a potential biomarker for adverse events during combination antiretroviral therapy for hiv
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5766130/
https://www.ncbi.nlm.nih.gov/pubmed/29329318
http://dx.doi.org/10.1371/journal.pone.0191069
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