Dataset Information

Acylcarnitines and Genetic Variation in Fat Oxidation Genes in HIV-infected, Antiretroviral-treated Children With and Without Myopathy.

ABSTRACT:

Background

Mitochondrial toxicity resulting in myopathy and lactic acidosis has been described in antiretroviral (ARV)-exposed patients. We hypothesized that myopathy in HIV-infected, ARV-treated children would be associated with metabolic (acylcarnitines) and genetic (variants in metabolic genes) markers of dysfunctional fatty acid oxidation (FAO).

Methods

Acylcarnitine profiles (ACP) were analyzed for 74 HIV-infected children on nucleoside reverse transcriptase inhibitor (NRTI)-containing ARV. Thirty-seven participants with ≥2 creatine kinase measurements >500 IU (n = 18) or evidence of echocardiographic cardiomyopathy (n = 19) were matched with 37 participants without myopathy. Single nucleotide polymorphisms (SNPs) in FAO genes were also evaluated.

Results

Abnormal ACP was 73% (95% CI: 56%-86%) and 62% (95% CI: 45%-78%) in the myopathic and nonmyopathic groups, respectively. No significant association was found between myopathy and having an abnormal ACP (OR = 2.10, P = 0.22). In univariate analysis, a 1-year increase in NRTI use was associated with a 20% increase in odds of at least 1 ACP abnormality [OR (95% CI) = 1.20 (1.03-1.41); P = 0.02), and a 1-year increase in protease inhibitor use was associated with 28% increase in the odds of having at least 1 ACP abnormality [OR (95% CI) = 1.28 (1.07-1.52); P = 0.006). Three SNPs, all in the gene for the carnitine transporter ( SLC22A5 ), were associated with the cardiomyopathy phenotype.

Conclusion

FAO appears to be altered in HIV-infected children with and without myopathy, but abnormal FAO does not fully explain myopathy in ARV-exposed children. Further study of SLC22A5 variation in ARV-exposed people is warranted carnitine transporter dysfunction-related cardiomyopathy may be treatable.

SUBMITTER: Kirmse B

PROVIDER: S-EPMC9288497 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Publications

Acylcarnitines and Genetic Variation in Fat Oxidation Genes in HIV-infected, Antiretroviral-treated Children With and Without Myopathy.

Kirmse Brian B Hobbs Charlotte C Aaron Lisa L Montepiedra Grace G Summar Marshall M Williams Paige L PL Smith Caitlin J CJ Van Dyke Russell R Yu Chunli C Ryckman Kelli K KK Borkowsky William W

The Pediatric infectious disease journal 20220713 8

<h4>Background</h4>Mitochondrial toxicity resulting in myopathy and lactic acidosis has been described in antiretroviral (ARV)-exposed patients. We hypothesized that myopathy in HIV-infected, ARV-treated children would be associated with metabolic (acylcarnitines) and genetic (variants in metabolic genes) markers of dysfunctional fatty acid oxidation (FAO).<h4>Methods</h4>Acylcarnitine profiles (ACP) were analyzed for 74 HIV-infected children on nucleoside reverse transcriptase inhibitor (NRTI)- ...[more]

PMID: 35622436

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Project description:BACKGROUND:Hepatitis B (HBV) and Human Immunodeficiency Virus (HIV) share common risk factors for exposure. Co-infected patients have an increased liver-related mortality risk and may have accelerated HIV progression. The epidemiology and demographic characteristics of HIV-HBV co-infection in Canada remain poorly defined. We compared the demographic and clinical characteristics and factors associated with advanced hepatic fibrosis between HIV and HIV-HBV co-infected patients. METHODS:A retrospective cohort analysis was conducted using data from the Canadian Observational Cohort (CANOC) Collaboration, including eight sites from British Columbia, Quebec, and Ontario. Eligible participants were HIV-infected patients who initiated combination ARV between January 1, 2000 and December 14, 2014. Demographic and clinical characteristics were compared between HIV-HBV co-infected and HIV-infected groups using chi-square or Fisher exact tests for categorical variables, and Wilcoxon's Rank Sum test for continuous variables. Liver fibrosis was estimated by the AST to Platelet Ratio Index (APRI). RESULTS:HBV status and APRI values were available for 2419 cohort participants. 199 (8%) were HBV co-infected. Compared to HIV-infected participants, HIV-HBV co-infected participants were more likely to use injection drugs (28% vs. 21%, p = 0.03) and be HCV-positive (31%, vs. 23%, p = 0.02). HIV-HBV co-infected participants had lower baseline CD4 T cell counts (188 cells/mm3, IQR: 120-360) compared to 235 cells/mm3 in HIV-infected participants (IQR: 85-294) (p = 0.0002) and higher baseline median APRI scores (0.50 vs. 0.37, p < 0.0001). This difference in APRI was no longer clinically significant at follow-up (0.32 vs. 0.30, p = 0.03). HIV-HBV co-infected participants had a higher mortality rate compared to HIV-infected participants (11% vs. 7%, p = 0.02). CONCLUSION:The prevalence, demographic and clinical characteristics of the HIV-HBV co-infected population in Canada is described. HIV-HBV co-infected patients have higher mortality, more advanced CD4 T cell depletion, and liver fibrosis that improves in conjunction with ARV therapy. The high prevalence of unknown HBV status demonstrates a need for increased screening among HIV-infected patients in Canada.

Dataset Information

Acylcarnitines and Genetic Variation in Fat Oxidation Genes in HIV-infected, Antiretroviral-treated Children With and Without Myopathy.

Background

Methods

Results

Conclusion

Publications

Acylcarnitines and Genetic Variation in Fat Oxidation Genes in HIV-infected, Antiretroviral-treated Children With and Without Myopathy.

Similar Datasets

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