title: HIV-associated CD4+/CD8+ depletion in infancy is associated with neurometabolic reductions in the basal ganglia at age 5 years despite early antiretroviral therapy.
abstract: Investigating consequences of early or late antiretroviral therapy (ART) initiation in infancy on young brain development using magnetic resonance spectroscopy.
  
  
  
  Most pediatric HIV/ART-related neurological studies are from neuropsychological/clinical perspectives. Magnetic resonance spectroscopy can elucidate the mechanisms underpinning neurocognitive outcomes by quantifying the brain's chemical condition through localized metabolism to provide insights into health and development.
  
  
  
  Basal ganglia metabolite concentrations were assessed in thirty-eight 5-year-old HIV-infected children previously participating in a randomized trial comparing early limited ART to deferred continuous ART, as well as 15 uninfected controls (12 HIV exposed). Metabolite levels were compared between 26 infected children who initiated ART at/before 12 weeks and 12 who initiated afterward, and were correlated with clinical HIV and treatment-related measures.
  
  
  
  HIV-infected children initiating ART after 12 weeks had lower creatine, choline and glutamate (P < 0.05) than those initiating ART at/before 12 weeks. The CD4/CD8 ratio at baseline correlated with N-acetyl-aspartate (r = 0.56, P = 0.003) and choline (r = 0.36, P = 0.03) at 5 years, irrespective of treatment regimen and ART interruption. In comparison with uninfected controls, 80% of whom were HIV-exposed in utero, children on early treatment had higher N-acetyl-aspartate (P = 0.006) and choline (P = 0.03).
  
  
  
  Despite early ART (<12 weeks), low baseline CD4/CD8 predicts brain metabolite levels in later childhood. Also, HIV exposure and antiretroviral exposure for preventing vertical HIV transmission may hinder metabolite health, but needs further investigation.
authors.affiliation: aMRC/UCT Medical Imaging Research Unit, Department of Human Biology, Faculty of Health Sciences, University of Cape Town bChildren's Infectious Diseases Clinical Research Unit, Department of Paediatrics & Child Health, Tygerberg Children's Hospital and Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa cA.A. Martinos Centre for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown dDepartment of Radiology, Harvard Medical School, Boston, Massachusetts, USA eDepartment of Statistical Sciences, Faculty of Sciences, University of Cape Town, South Africa fOxford Centre for Clinical Magnetic Resonance Research (OCMR), Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Kenneth K
authors.initials: KK
authors.lastname: Mbugua
authors.forename: Martha J
authors.initials: MJ
authors.lastname: Holmes
authors.forename: Mark F
authors.initials: MF
authors.lastname: Cotton
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Ratai
authors.forename: Francesca
authors.initials: F
authors.lastname: Little
authors.forename: Aaron T
authors.initials: AT
authors.lastname: Hess
authors.forename: Els
authors.initials: E
authors.lastname: Dobbels
authors.forename: Andre J W
authors.initials: AJ
authors.lastname: Van der Kouwe
authors.forename: Barbara
authors.initials: B
authors.lastname: Laughton
authors.forename: Ernesta M
authors.initials: EM
authors.lastname: Meintjes
mesh_terms: D015526:AIDS Dementia Complex / Q000503:physiopathology*; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D001479:Basal Ganglia / Q000737:chemistry*; D001685:Biological Factors / Q000032:analysis*; D001921:Brain / Q000000981:diagnostic imaging; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D018655:Lymphocyte Count; D009682:Magnetic Resonance Spectroscopy; D008297:Male
chemical_list: D044966:Anti-Retroviral Agents; D001685:Biological Factors