1. Elevated Blood Mitochondrial DNA in Early Life Among Uninfected Children Exposed to Human Immunodeficiency Virus and Combination Antiretroviral Therapy in utero
- Author
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Jason Brophy, Sara Saberi, Deborah Money, Neora Pick, Mary Lou Smith, Hugo Soudeyns, Children (Children), Ari Bitnun, Ariane Alimenti, Hélène C. F. Côté, Melanie C.M. Murray, Cihr Team in Cellular Aging, Michael Silverman, Fatima Kakkar, Patricia A. Janssen, Arianne Albert, Jerilynn C. Prior, Mayanne Zhu, Joel Singer, Normand Lapointe, Hiv Comorbidities in Women, Abhinav Ajaykumar, and Women: AntiRetrovirals
- Subjects
0301 basic medicine ,Cart ,Male ,Mitochondrial DNA ,Anti-HIV Agents ,Physiology ,HIV Infections ,Mitochondrion ,DNA, Mitochondrial ,03 medical and health sciences ,Major Articles and Brief Reports ,0302 clinical medicine ,Pregnancy ,Placenta ,Antiretroviral Therapy, Highly Active ,medicine ,Immunology and Allergy ,Humans ,030212 general & internal medicine ,Longitudinal Studies ,Pregnancy Complications, Infectious ,business.industry ,Transmission (medicine) ,Infant, Newborn ,Gestational age ,Infant ,medicine.disease ,Infectious Disease Transmission, Vertical ,3. Good health ,030104 developmental biology ,Infectious Diseases ,medicine.anatomical_structure ,Cross-Sectional Studies ,In utero ,Child, Preschool ,Prenatal Exposure Delayed Effects ,Female ,business - Abstract
BackgroundCombination antiretroviral therapy (cART) during pregnancy prevents vertical transmission, but many antiretrovirals cross the placenta and several can affect mitochondria. Exposure to maternal human immunodeficiency virus (HIV) and/or cART could have long-term effects on children who are HIV exposed and uninfected (CHEU). Our objective was to compare blood mitochondrial DNA (mtDNA) content in CHEU and children who are HIV unexposed and uninfected (CHUU), at birth and in early life.MethodsWhole-blood mtDNA content at birth and in early life (age 0–3 years) was compared cross-sectionally between CHEU and CHUU. Longitudinal changes in mtDNA content among CHEU was also evaluated.ResultsAt birth, CHEU status and younger gestational age were associated with higher mtDNA content. These remained independently associated with mtDNA content in multivariable analyses, whether considering all infants, or only those born at term. Longitudinally, CHEU mtDNA levels remained unchanged during the first 6 months of life, and gradually declined thereafter. A separate age- and sex-matched cross-sectional analysis (in 214 CHEU and 214 CHUU) illustrates that the difference in mtDNA between the groups remains detectable throughout the first 3 years of life.ConclusionThe persistently elevated blood mtDNA content observed among CHEU represents a long-term effect, possibly resulting from in utero stresses related to maternal HIV and/or cART. The clinical impact of altered mtDNA levels is unclear.
- Published
- 2020