Metabolic events in HIV-infected patients using abacavir are associated with erythrocyte inosine triphosphatase activity.
J Antimicrob Chemother
; 74(1): 157-164, 2019 01 01.
Article
em En
| MEDLINE
| ID: mdl-30304447
ABSTRACT
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 <4 mmol IMP/mmol Hb/h was considered decreased. ITPA polymorphisms tested were c.94C>A (rs1127354) and c.124â+â21A>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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pirofosfatases
/
Didesoxinucleosídeos
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Infecções por HIV
/
Inibidores da Transcriptase Reversa
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Eritrócitos
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Hipercolesterolemia
/
Hipertensão
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
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Aged
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
J Antimicrob Chemother
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Holanda