Acylcarnitines and Genetic Variation in Fat Oxidation Genes in HIV-infected, Antiretroviral-treated Children With and Without Myopathy. Issue 8 (13th July 2022)

• Record Type: Journal Article
• Authors: Kirmse, Brian; Hobbs, Charlotte; Aaron, Lisa; Montepiedra, Grace; Summar, Marshall; Williams, Paige L.; Smith, Caitlin J.; Van Dyke, Russell; Yu, Chunli; Ryckman, Kelli K.; Borkowsky, William
• Other Names: Chadwick Ellen author non-byline.; Sanders Margaret Ann author non-byline.; Malee Kathleen author non-byline.; Pyun Yoonsun author non-byline.; Paul Mary author non-byline.; Buschur Shelley author non-byline.; McMullen-Jackson Chivon author non-byline.; Harris Lynnette author non-byline.; Purswani Murli author non-byline.; Baig Mahboobullah Mirza author non-byline.; Villegas Alma author non-byline.; Robinson Lisa- Gaye author non-byline.; Navarro Sandra author non-byline.; Garvie Patricia author non-byline.; Burchett Sandra K. author non-byline.; Pinsky Rebecca author non-byline.; Cassidy Adam R. author non-byline.; Wiznia Andrew author non-byline.; Burey Marlene author non-byline.; Shaw Ray author non-byline.; Dieudonne Arry author non-byline.; Bettica Linda author non-byline.; Johnson Juliette author non-byline.; Surowiec Karen author non-byline.; Chen Janet S. author non-byline.; White Taesha author non-byline.; Grant Mitzie author non-byline.; Knapp Katherine author non-byline.; Russell-Bell Jamie author non-byline.; Wilkins Megan author non-byline.; Odero Erick author non-byline.; Acevedo-Flores Midnela author non-byline.; Rios Heida author non-byline.; Olivera Vivian author non-byline.; Silio Margarita author non-byline.; Gabriel Medea author non-byline.; Sirois Patricia author non-byline.; Spector Stephen A. author non-byline.; Loughran Megan author non-byline.; Figueroa Veronica author non-byline.; Nichols Sharon author non-byline.; McFarland Elizabeth author non-byline.; Chambers Carrie author non-byline.; Barr Emily author non-byline.; Glidden Mary author non-byline.; Scott Gwendolyn author non-byline.; Alvarez Grace author non-byline.; Caffroni Juan author non-byline.; Cuadra Anai author non-byline.;
• Is Part Of: Pediatric infectious disease journal. Volume 41:Issue 8(2022)
• Page Start: e306
• Page End: e311
• Publication Date: 2022-07-13
• Subjects: HIV -- fatty acid oxidation -- acylcarnitines -- myopathy -- cardiomyopathy; Communicable diseases in children -- Periodicals; Infection in children -- Periodicals; 618.929
• DOI: 10.1097/INF.0000000000003586
• Languages: English
• ISSNs: 0891-3668

Abstract

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.