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Abnormal newborn screens and acylcarnitines in HIV-exposed and ARV-exposed infants
Brian Kirmse1, Charlotte V Hobbs, Inga Peter
1Genetics & Metabolism, Children's National Medical Center, Washington, DC 20016, USA. bkirmse@cnmc.org
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.
Insights
Antiretroviral drug (ARV) exposure in newborns is linked to abnormal newborn metabolic screens and impaired fatty acid oxidation. Further studies are needed to confirm these findings and their clinical significance.
Area of Science:
- Biochemistry
- Neonatal Metabolism
- Pharmacology
Background:
- Antiretroviral drugs (ARV), particularly nucleoside analogs, are known to cause mitochondrial oxidative phosphorylation toxicity.
- Metabolic pathways like fatty acid, organic acid, and amino acid metabolism rely on oxidative phosphorylation but haven't been fully assessed for ARV toxicity.
Purpose of the Study:
- To investigate potential toxicity of antiretroviral drugs (ARV) on intermediary metabolism in newborns.
- To examine the association between HIV/ARV exposure and newborn metabolic screening abnormalities.
Main Methods:
- Analysis of newborn screening data from New York, comparing HIV-positive and HIV-negative neonates.
- Measurement of acylcarnitine levels in ARV-exposed versus ARV-unexposed HIV-exposed infants to assess fatty and organic acid metabolism.
Main Results:
- HIV screen-positive infants showed a higher rate of abnormal newborn metabolic screens (2.2% vs. 1.2%) compared to the general population, often related to mitochondrial metabolism.
- Abnormal acylcarnitine levels were significantly more frequent in ARV-exposed infants (43%) than in unexposed infants (0%).
Conclusions:
- Elevated abnormal metabolic screens in HIV-positive neonates suggest HIV or ARV exposure impacts intermediary metabolism.
- Increased abnormal acylcarnitine levels in ARV-exposed infants indicate potential ARV-induced perturbation of fatty acid oxidation.
- Further research is warranted to validate these findings and determine their clinical implications.
