TY - JOUR
T1 - Metabolic events in HIV-infected patients using abacavir are associated with erythrocyte inosine triphosphatase activity
AU - Peltenburg, N. Chantal
AU - Bierau, Jorgen
AU - Schippers, Jolanda A.
AU - Lowe, Selwyn H.
AU - Paulussen, Aimee D. C.
AU - van den Bosch, Bianca J. C.
AU - Leers, Mathie P. G.
AU - Andrinopoulou, Eleni-Rosalina
AU - Bakker, Jaap A.
AU - Verbon, Annelies
N1 - Funding Information:
This work was supported by an unrestricted scientific grant by Janssen pharmaceutical companies of Johnson & Johnson to A. V.
Publisher Copyright:
© 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.
PY - 2019/1
Y1 - 2019/1
N2 - Objectives: Abacavir use has been associated with an increased risk of cardiovascular disease (CVD) and metabolic events in HIV-infected patients, although this finding was not consistently found. It is unclear whether abacavir only increases this risk in subpopulations of HIV-infected patients. It may be hypothesized that inosine 5'-triphosphate pyrophosphohydrolase (ITPase), an enzyme involved in the metabolism of purine analogues used in HIV treatment, plays a role in the risk of CVD and metabolic events in HIV-infected patients.Methods: ITPase activity and ITPA genotype were determined in 393 HIV-infected patients. ITPase activity A (rs1127354) and c.124 + 21A>C (rs7270101). ORs were determined using generalized estimating equation models for developing CVD in patients who had ever been exposed to abacavir, tenofovir or didanosine and for developing metabolic events in patients currently using these drugs.Results: In patients using abacavir, metabolic events were associated with ITPase activity. No association was demonstrated for tenofovir or didanosine. The OR for metabolic events was 3.11 in patients using abacavir with normal ITPase activity (95% CI 1.34-7.21; P = 0.008) compared with patients with decreased ITPase activity [adjusted for age, BMI, cumulative duration of combination ART (cART) use and the use of PI and NNRTI]. CVD was not associated with ITPase activity or ITPA genotype.Conclusions: This study shows, for the first time, that ITPase activity is associated with the occurrence of metabolic events in patients using abacavir. Further studies are needed to confirm this association and to elucidate the possible mechanism.
AB - Objectives: Abacavir use has been associated with an increased risk of cardiovascular disease (CVD) and metabolic events in HIV-infected patients, although this finding was not consistently found. It is unclear whether abacavir only increases this risk in subpopulations of HIV-infected patients. It may be hypothesized that inosine 5'-triphosphate pyrophosphohydrolase (ITPase), an enzyme involved in the metabolism of purine analogues used in HIV treatment, plays a role in the risk of CVD and metabolic events in HIV-infected patients.Methods: ITPase activity and ITPA genotype were determined in 393 HIV-infected patients. ITPase activity A (rs1127354) and c.124 + 21A>C (rs7270101). ORs were determined using generalized estimating equation models for developing CVD in patients who had ever been exposed to abacavir, tenofovir or didanosine and for developing metabolic events in patients currently using these drugs.Results: In patients using abacavir, metabolic events were associated with ITPase activity. No association was demonstrated for tenofovir or didanosine. The OR for metabolic events was 3.11 in patients using abacavir with normal ITPase activity (95% CI 1.34-7.21; P = 0.008) compared with patients with decreased ITPase activity [adjusted for age, BMI, cumulative duration of combination ART (cART) use and the use of PI and NNRTI]. CVD was not associated with ITPase activity or ITPA genotype.Conclusions: This study shows, for the first time, that ITPase activity is associated with the occurrence of metabolic events in patients using abacavir. Further studies are needed to confirm this association and to elucidate the possible mechanism.
KW - ACUTE LYMPHOBLASTIC-LEUKEMIA
KW - CARDIOVASCULAR-DISEASE
KW - MYOCARDIAL-INFARCTION
KW - ENDOTHELIAL DYSFUNCTION
KW - LIFE EXPECTANCY
KW - RISK-FACTORS
KW - CYCLASE
KW - THERAPY
KW - POLYMORPHISM
KW - STIMULATION
U2 - 10.1093/jac/dky383
DO - 10.1093/jac/dky383
M3 - Article
C2 - 30304447
SN - 0305-7453
VL - 74
SP - 157
EP - 164
JO - Journal of Antimicrobial Chemotherapy
JF - Journal of Antimicrobial Chemotherapy
IS - 1
ER -