PMID- 29329318
OWN - NLM
STAT- MEDLINE
DCOM- 20180215
LR  - 20231213
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 13
IP  - 1
DP  - 2018
TI  - Erythrocyte Inosine triphosphatase activity: A potential biomarker for adverse 
      events during combination antiretroviral therapy for HIV.
PG  - e0191069
LID - 10.1371/journal.pone.0191069 [doi]
LID - e0191069
AB  - 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.
FAU - Peltenburg, N Chantal
AU  - Peltenburg NC
AUID- ORCID: 0000-0002-8723-3397
AD  - Department of Internal medicine, Division Infectious Diseases, Erasmus Medical 
      Center, Rotterdam, The Netherlands.
AD  - Department of Medical Microbiology and Infectious Diseases, Erasmus Medical 
      Center, Rotterdam, The Netherlands.
FAU - Bierau, Jorgen
AU  - Bierau J
AD  - Department of Clinical Genetics, Maastricht University Medical Center, 
      Maastricht, The Netherlands.
FAU - Bakker, Jaap A
AU  - Bakker JA
AD  - Department of Clinical Chemistry and Laboratory Medicine, Leiden University 
      Medical Center, Leiden, The Netherlands.
FAU - Schippers, Jolanda A
AU  - Schippers JA
AD  - Department of Integrated Care, Maastricht University Medical Center, Maastricht, 
      The Netherlands.
FAU - Lowe, Selwyn H
AU  - Lowe SH
AD  - Department of internal medicine, Division Infectious Diseases, Maastricht 
      University Medical Center, Maastricht, The Netherlands.
AD  - Department of Medical Microbiology, School of CAPHRI, Maastricht University 
      Medical Center, Maastricht, The Netherlands.
FAU - Paulussen, Aimee D C
AU  - Paulussen ADC
AD  - Department of Clinical Genetics, Maastricht University Medical Center, 
      Maastricht, The Netherlands.
FAU - van den Bosch, Bianca J C
AU  - van den Bosch BJC
AD  - Department of Clinical Genetics, Maastricht University Medical Center, 
      Maastricht, The Netherlands.
FAU - Leers, Mathie P G
AU  - Leers MPG
AD  - Department of Clinical Chemistry & Hematology, Zuyderland Medical Center, 
      Heerlen, The Netherlands.
FAU - Hansen, Bettina E
AU  - Hansen BE
AD  - Department of Gastroenterology & Hepatology, Erasmus Medical Center, Rotterdam, 
      The Netherlands.
FAU - Verbon, Annelies
AU  - Verbon A
AD  - Department of Internal medicine, Division Infectious Diseases, Erasmus Medical 
      Center, Rotterdam, The Netherlands.
AD  - Department of Medical Microbiology and Infectious Diseases, Erasmus Medical 
      Center, Rotterdam, The Netherlands.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180112
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Biomarkers)
RN  - EC 3.6.1.- (Pyrophosphatases)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Anti-HIV Agents/administration & dosage/*therapeutic use
MH  - Biomarkers/*blood
MH  - Drug Therapy, Combination
MH  - Erythrocytes/*enzymology
MH  - Female
MH  - HIV Infections/*drug therapy
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Pyrophosphatases/*blood
MH  - Young Adult
MH  - Inosine Triphosphatase
PMC - PMC5766130
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2018/01/13 06:00
MHDA- 2018/02/16 06:00
PMCR- 2018/01/12
CRDT- 2018/01/13 06:00
PHST- 2017/06/09 00:00 [received]
PHST- 2017/12/26 00:00 [accepted]
PHST- 2018/01/13 06:00 [entrez]
PHST- 2018/01/13 06:00 [pubmed]
PHST- 2018/02/16 06:00 [medline]
PHST- 2018/01/12 00:00 [pmc-release]
AID - PONE-D-17-22115 [pii]
AID - 10.1371/journal.pone.0191069 [doi]
PST - epublish
SO  - PLoS One. 2018 Jan 12;13(1):e0191069. doi: 10.1371/journal.pone.0191069. 
      eCollection 2018.