title: Abnormal newborn screens and acylcarnitines in HIV-exposed and ARV-exposed infants.
abstract: BACKGROUND
  Antiretroviral drugs (ARV), specifically nucleoside analogs, are toxic to mitochondrial oxidative phosphorylation. Other metabolic pathways, such as fatty acid oxidation, organic acid metabolism and amino acid metabolism, are dependent on normal oxidative phosphorylation but remain unexamined as potential points of ARV toxicity.
  
  
  METHODS
  We analyzed newborn screening data from New York and compared proportions of abnormal newborn metabolic screens in HIV antibody screen-positive and HIV screen-negative neonates. Subsequently, we compared acylcarnitine levels in ARV-exposed (n = 16) and ARV-unexposed (n = 14) HIV-exposed infants to assess for dysfunctional fatty and organic acid metabolism.
  
  
  RESULTS
  : The rate of abnormal newborn metabolic screens in HIV screen-positive infants was higher than that in the general population (2.2% versus 1.2%; P = 0.00025), most of which were for disorders of mitochondria-related metabolism. Abnormal acylcarnitine levels occurred more frequently in ARV-exposed compared with ARV-unexposed infants (43% versus 0%; P = 0.02).
  
  
  CONCLUSIONS
  A higher proportion of positive metabolic screens in HIV screen-positive neonates suggests that HIV or ARV exposure is associated with dysfunctional intermediary metabolism in newborns. Abnormal acylcarnitine levels were more frequent in ARV-exposed infants, suggesting that ARV may perturb normal fatty acid oxidation in some infants. Studies designed to validate and determine the clinical significance of these findings are warranted.
authors.affiliation: Genetics & Metabolism, Children's National Medical Center, Washington, DC 20016, USA. bkirmse@cnmc.org
authors.forename: Brian
authors.initials: B
authors.lastname: Kirmse
authors.forename: Charlotte V
authors.initials: CV
authors.lastname: Hobbs
authors.forename: Inga
authors.initials: I
authors.lastname: Peter
authors.forename: Bryan
authors.initials: B
authors.lastname: Laplante
authors.forename: Michele
authors.initials: M
authors.lastname: Caggana
authors.forename: Karen
authors.initials: K
authors.lastname: Kloke
authors.forename: Kimiyo
authors.initials: K
authors.lastname: Raymond
authors.forename: Marshall
authors.initials: M
authors.lastname: Summar
authors.forename: William
authors.initials: W
authors.lastname: Borkowsky
mesh_terms: D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D002331:Carnitine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D016022:Case-Control Studies; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism* / Q000517:prevention & control; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000097:blood / Q000175:diagnosis / Q000378:metabolism* / Q000821:virology; D015997:Neonatal Screening; D009518:New York
chemical_list: D044966:Anti-Retroviral Agents; C116917:acylcarnitine; D002331:Carnitine