title: Effects of paediatric HIV infection on childhood vasculature.
abstract: Human immunodeficiency virus (HIV) infection may alter childhood vascular properties and influence future cardiovascular risk. Whether vascular changes are associated with HIV infection per se or antiretroviral therapy (ART) is unknown. We investigated the effects of ART-naive or ART-exposed HIV infection in children on childhood vascular characteristics.
  
  
  
  We performed vascular ultrasound to measure carotid intima media thickness (cIMT), distensibility, and elastic modulus on 114 children with vertically acquired HIV infection (56 ART-naive, 58 ART treated) and 51 healthy children in Jakarta, Indonesia. Children also underwent clinical and blood examinations. We used general linear modelling to estimate associations between HIV infection/treatment status and vascular characteristics with adjustment for confounders or possible mediators. Vascular measurements were successful in 42 ART-naive HIV-infected [median age 4.0 years (min 0.4-max 11.5)]; 53 ART-treated HIV infected [5.7 years (0.6-12.2), median ART duration 2.4 years (0.1-9.9)]; and 48 healthy children, 6.5 years (2.4-14.0). The ART-naive HIV infected had thicker cIMT (difference 70.4 µm, 95% CI 32.1-108.7, P < 0.001), adjusted for age, sex, socioeconomic status, parental smoking, body mass index, systolic and diastolic blood pressure, LDL cholesterol, and HbA1c. Addition of high-sensitivity C-reactive protein (hs-CRP) level to the model did not affect the results (71.6 µm, 31.9-111.2, P = 0.001). The ART-exposed children had similar cIMT dimensions to healthy children. Distensibility was not significantly different between HIV infected, either ART-naive or -exposed, and healthy children, but adjusted analysis including only ART-exposed children with controlled HIV (CD4+ ≥200/mm3or CD4+ ≥15%) showed that the ART-exposed had an increased elastic modulus (difference 37.9 kPa, 95% CI 6.5-69.3, P = 0.02), and following adjustment for hs-CRP (35.5 kPa, 95% CI 4.2-66.8, P = 0.03).
  
  
  
  ART-naive HIV infection in children is associated with increased cIMT. Children with ART-controlled HIV may have increased arterial stiffness, although further confirmation is required.
authors.affiliation: Department of Child Health, Faculty of Medicine, University of Indonesia-Cipto Mangunkusumo National General Hospital, Jl. Diponegoro No. 71, Jakarta 10430, Indonesia nikmah@ikafkui.org.|Julius Global Health, Julius Centre for Health Sciences and Primary Care, The University Medical Centre Utrecht, Utrecht, The Netherlands.|Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Melbourne, Victoria, Australia.
authors.forename: Nikmah S
authors.initials: NS
authors.lastname: Idris
authors.affiliation: Julius Global Health, Julius Centre for Health Sciences and Primary Care, The University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Diederick E
authors.initials: DE
authors.lastname: Grobbee
authors.affiliation: Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Melbourne, Victoria, Australia.|Department of Paediatrics, University of Melbourne, Parkville, Melbourne, Victoria, Australia.|Department of Paediatrics, Monash University, Melbourne, Victoria, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Burgner
authors.affiliation: Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Melbourne, Victoria, Australia.|Department of Paediatrics, University of Melbourne, Parkville, Melbourne, Victoria, Australia.
authors.forename: Michael M H
authors.initials: MM
authors.lastname: Cheung
authors.affiliation: Department of Child Health, Faculty of Medicine, University of Indonesia-Cipto Mangunkusumo National General Hospital, Jl. Diponegoro No. 71, Jakarta 10430, Indonesia.|Julius Global Health, Julius Centre for Health Sciences and Primary Care, The University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Nia
authors.initials: N
authors.lastname: Kurniati
authors.affiliation: Julius Global Health, Julius Centre for Health Sciences and Primary Care, The University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Cuno S P M
authors.initials: CS
authors.lastname: Uiterwaal
mesh_terms: D002097:C-Reactive Protein; D002318:Cardiovascular Diseases; D059168:Carotid Intima-Media Thickness; D002648:Child; D002675:Child, Preschool; D015658:HIV Infections; D006801:Humans; D007223:Infant; D012307:Risk Factors
chemical_list: D002097:C-Reactive Protein
keywords: Children; Distensibility; HIV; Intima media thickness