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.
From the *Genetics & Metabolism, Children’s National Medical Center, Washington, DC; †National Institutes of Health (NIAID), Laboratory of Malaria Immunology and Vaccinology, Rockville, MD; ‡Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY; §New York State Department of Health/Wadsworth Center, Albany, NY; ¶Biochemical Genetics Laboratory, Mayo Medical Laboratories, Rochester, MN; and ║Division of Infectious Disease and Immunology, Department of Pediatrics, New York University/Bellevue Medical Center, New York, NY.
Accepted for publication May 01, 2012.
BK and CVH contributed equally to this work.
Supported by National Institutes of Health T32 Grant, New York State (Empire Clinical Research Investigator Program) and Thrasher Research Fund. The authors have no other funding or conflicts of interest to disclose.
Address for correspondence: Brian Kirmse, MD, Genetics & Metabolism, Children’s National Medical Center, 111 Michigan Avenue, NW, Suite 4800, Washington, DC 20016. E-mail: firstname.lastname@example.org.
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