Lower mitochondrial DNA and altered mitochondrial fuel metabolism in HIV-exposed uninfected infants in Cameroon

Jennifer Jao, Kathleen M. Powis, Brian Kirmse, Chunli Yu, Fanny Epie, Emmanuel Nshom, Elaine J. Abrams, Rhoda S. Sperling, Derek Leroith, Mitchell E. Geffner, Irwin J. Kurland, Hélène C.F. Côté

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Objective: Evaluate blood mitochondrial DNA (mtDNA) content in HIV/antiretroviral-exposed uninfected (HEU) vs. HIV-unexposed uninfected (HUU) infants and investigate differences in mitochondrial-related metabolites by exposure group. Design: We enrolled a prospective cohort of HIV-infected and HIV-uninfected pregnant woman/infant pairs in Cameroon. Methods: Dried blood spot mtDNA:nuclear DNA ratio was measured by monochrome multiplex quantitative polymerase chain reaction in HEU infants exposed to in-utero antiretrovirals and postnatal zidovudine (HEU-Z) or nevirapine (HEU-N), and in HUU infants at 6 weeks of life. Acylcarnitines and branch-chain amino acids (BCAAs) were measured via tandem mass spectrometry and consolidated into seven uncorrelated components using principal component analysis. Linear regression models were fit to assess the association between in-utero/postnatal HIV/antiretroviral exposure and infant mtDNA, adjusting for confounders and principal component analysis-derived acylcarnitine/BCAA component scores. Results: Of 364 singleton infants, 38 were HEU-Z, 117 HEU-N, and 209 HUU. Mean mtDNA content was lowest in HEU-Z infants (140 vs. 160 in HEU-N vs. 174 in HUU, P=0.004). After adjusting for confounders, HEU-Z infants remained at increased risk for lower mtDNA content compared with HUU infants (β: -4.46, P=0.045), whereas HEU-N infants did not, compared with HUU infants (β: -1.68, P=0.269. Furthermore, long-chain acylcarnitines were associated with lower (β: -2.35, P=0.002) and short-chain and BCAA-related acylcarnitines were associated with higher (β: 2.96, P=0.001) mtDNA content. Conclusion: Compared with HUU infants, HEU infants receiving postnatal zidovudine appear to be at increased risk for decreased blood mtDNA content which may be associated with altered mitochondrial fuel utilization in HEU-Z infants.

Original languageEnglish (US)
Pages (from-to)2475-2481
Number of pages7
JournalAIDS
Volume31
Issue number18
DOIs
StatePublished - Nov 28 2017

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Cameroon
Mitochondrial DNA
HIV
Zidovudine
Principal Component Analysis
Amino Acids
Linear Models
Dried Blood Spot Testing

Keywords

  • acylcarnitines
  • branched-chain amino acids
  • HIV-exposed infants
  • mitochondria
  • mitochondrial DNA
  • zidovudine infant prophylaxis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Jao, J., Powis, K. M., Kirmse, B., Yu, C., Epie, F., Nshom, E., ... Côté, H. C. F. (2017). Lower mitochondrial DNA and altered mitochondrial fuel metabolism in HIV-exposed uninfected infants in Cameroon. AIDS, 31(18), 2475-2481. https://doi.org/10.1097/QAD.0000000000001647

Lower mitochondrial DNA and altered mitochondrial fuel metabolism in HIV-exposed uninfected infants in Cameroon. / Jao, Jennifer; Powis, Kathleen M.; Kirmse, Brian; Yu, Chunli; Epie, Fanny; Nshom, Emmanuel; Abrams, Elaine J.; Sperling, Rhoda S.; Leroith, Derek; Geffner, Mitchell E.; Kurland, Irwin J.; Côté, Hélène C.F.

In: AIDS, Vol. 31, No. 18, 28.11.2017, p. 2475-2481.

Research output: Contribution to journalArticle

Jao, J, Powis, KM, Kirmse, B, Yu, C, Epie, F, Nshom, E, Abrams, EJ, Sperling, RS, Leroith, D, Geffner, ME, Kurland, IJ & Côté, HCF 2017, 'Lower mitochondrial DNA and altered mitochondrial fuel metabolism in HIV-exposed uninfected infants in Cameroon', AIDS, vol. 31, no. 18, pp. 2475-2481. https://doi.org/10.1097/QAD.0000000000001647
Jao, Jennifer ; Powis, Kathleen M. ; Kirmse, Brian ; Yu, Chunli ; Epie, Fanny ; Nshom, Emmanuel ; Abrams, Elaine J. ; Sperling, Rhoda S. ; Leroith, Derek ; Geffner, Mitchell E. ; Kurland, Irwin J. ; Côté, Hélène C.F. / Lower mitochondrial DNA and altered mitochondrial fuel metabolism in HIV-exposed uninfected infants in Cameroon. In: AIDS. 2017 ; Vol. 31, No. 18. pp. 2475-2481.
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abstract = "Objective: Evaluate blood mitochondrial DNA (mtDNA) content in HIV/antiretroviral-exposed uninfected (HEU) vs. HIV-unexposed uninfected (HUU) infants and investigate differences in mitochondrial-related metabolites by exposure group. Design: We enrolled a prospective cohort of HIV-infected and HIV-uninfected pregnant woman/infant pairs in Cameroon. Methods: Dried blood spot mtDNA:nuclear DNA ratio was measured by monochrome multiplex quantitative polymerase chain reaction in HEU infants exposed to in-utero antiretrovirals and postnatal zidovudine (HEU-Z) or nevirapine (HEU-N), and in HUU infants at 6 weeks of life. Acylcarnitines and branch-chain amino acids (BCAAs) were measured via tandem mass spectrometry and consolidated into seven uncorrelated components using principal component analysis. Linear regression models were fit to assess the association between in-utero/postnatal HIV/antiretroviral exposure and infant mtDNA, adjusting for confounders and principal component analysis-derived acylcarnitine/BCAA component scores. Results: Of 364 singleton infants, 38 were HEU-Z, 117 HEU-N, and 209 HUU. Mean mtDNA content was lowest in HEU-Z infants (140 vs. 160 in HEU-N vs. 174 in HUU, P=0.004). After adjusting for confounders, HEU-Z infants remained at increased risk for lower mtDNA content compared with HUU infants (β: -4.46, P=0.045), whereas HEU-N infants did not, compared with HUU infants (β: -1.68, P=0.269. Furthermore, long-chain acylcarnitines were associated with lower (β: -2.35, P=0.002) and short-chain and BCAA-related acylcarnitines were associated with higher (β: 2.96, P=0.001) mtDNA content. Conclusion: Compared with HUU infants, HEU infants receiving postnatal zidovudine appear to be at increased risk for decreased blood mtDNA content which may be associated with altered mitochondrial fuel utilization in HEU-Z infants.",
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AU - Epie, Fanny

AU - Nshom, Emmanuel

AU - Abrams, Elaine J.

AU - Sperling, Rhoda S.

AU - Leroith, Derek

AU - Geffner, Mitchell E.

AU - Kurland, Irwin J.

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N2 - Objective: Evaluate blood mitochondrial DNA (mtDNA) content in HIV/antiretroviral-exposed uninfected (HEU) vs. HIV-unexposed uninfected (HUU) infants and investigate differences in mitochondrial-related metabolites by exposure group. Design: We enrolled a prospective cohort of HIV-infected and HIV-uninfected pregnant woman/infant pairs in Cameroon. Methods: Dried blood spot mtDNA:nuclear DNA ratio was measured by monochrome multiplex quantitative polymerase chain reaction in HEU infants exposed to in-utero antiretrovirals and postnatal zidovudine (HEU-Z) or nevirapine (HEU-N), and in HUU infants at 6 weeks of life. Acylcarnitines and branch-chain amino acids (BCAAs) were measured via tandem mass spectrometry and consolidated into seven uncorrelated components using principal component analysis. Linear regression models were fit to assess the association between in-utero/postnatal HIV/antiretroviral exposure and infant mtDNA, adjusting for confounders and principal component analysis-derived acylcarnitine/BCAA component scores. Results: Of 364 singleton infants, 38 were HEU-Z, 117 HEU-N, and 209 HUU. Mean mtDNA content was lowest in HEU-Z infants (140 vs. 160 in HEU-N vs. 174 in HUU, P=0.004). After adjusting for confounders, HEU-Z infants remained at increased risk for lower mtDNA content compared with HUU infants (β: -4.46, P=0.045), whereas HEU-N infants did not, compared with HUU infants (β: -1.68, P=0.269. Furthermore, long-chain acylcarnitines were associated with lower (β: -2.35, P=0.002) and short-chain and BCAA-related acylcarnitines were associated with higher (β: 2.96, P=0.001) mtDNA content. Conclusion: Compared with HUU infants, HEU infants receiving postnatal zidovudine appear to be at increased risk for decreased blood mtDNA content which may be associated with altered mitochondrial fuel utilization in HEU-Z infants.

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