N Chantal Peltenburg1,2, Jörgen Bierau3, Jolanda A Schippers4, Selwyn H Lowe5,6, Aimée D C Paulussen3, Bianca J C van den Bosch3, Mathie P G Leers7, Eleni-Rosalina Andrinopoulou8, Jaap A Bakker9, Annelies Verbon1,2. 1. Department of Internal Medicine, Division of Infectious Diseases, Erasmus University Medical Center, Rotterdam, The Netherlands. 2. Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center, Rotterdam, The Netherlands. 3. Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands. 4. Department of Integrated Care, Maastricht University Medical Center, Maastricht, The Netherlands. 5. Department of Internal Medicine, Division of Infectious Diseases, Maastricht University Medical Center, Maastricht, The Netherlands. 6. Department of Medical Microbiology, School of CAPHRI, Maastricht University Medical Center, Maastricht, The Netherlands. 7. Department of Clinical Chemistry & Hematology, Zuyderland Medical Center, Heerlen, The Netherlands. 8. Department of Biostatistics, Erasmus University Medical Center, Rotterdam, The Netherlands. 9. Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, The Netherlands.
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.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.
Objectives:Abacavir use has been associated with an increased risk of cardiovascular disease (CVD) and metabolic events in HIV-infectedpatients, although this finding was not consistently found. It is unclear whether abacavir only increases this risk in subpopulations of HIV-infectedpatients. 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-infectedpatients. Methods: ITPase activity and ITPA genotype were determined in 393 HIV-infectedpatients. ITPase activity <4 mmol IMP/mmol Hb/h was considered decreased. ITPA polymorphisms tested were: c.94C>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.
Authors: Natalia A Osna; Rakesh Bhatia; Christopher Thompson; Surinder K Batra; Sushil Kumar; Yeonhee Cho; Gyongyi Szabo; Patricia E Molina; Steven A Weinman; Murali Ganesan; Kusum K Kharbanda Journal: Alcohol Date: 2020-06-01 Impact factor: 2.405
Authors: Willy Albert Flegel; Kshitij Srivastava; Tristan Michael Sissung; Barry Ronald Goldspiel; William Douglas Figg Journal: Vox Sang Date: 2020-09-30 Impact factor: 2.996