Blood Mitochondrial DNA Content in HIV-Exposed Uninfected Children with Autism Spectrum Disorder

Area of Science:

• Perinatology
• Neurodevelopmental Disorders
• Mitochondrial Biology

Background:

• Long-term outcomes for children exposed to maternal antiretroviral therapy (ART) are not fully understood.
• Both ART and autism spectrum disorder (ASD) are linked to mitochondrial alterations.
• Leukocyte mitochondrial DNA (mtDNA) content is a potential biomarker for mitochondrial dysfunction.

Purpose of the Study:

• To investigate the association between perinatal ART exposure and mitochondrial DNA content in HIV-exposed uninfected (HEU) children.
• To explore the relationship between leukocyte mtDNA content and ASD diagnosis in HEU children.
• To compare mtDNA content across different study groups: HEU with ASD, HEU without ASD, HIV-unexposed uninfected (HUU) controls, and HUU with ASD.

Main Methods:

• A cross-sectional, nested case-control study design was employed.
• HEU children with ASD were matched to HEU children without ASD, HUU controls, and HUU children with ASD.
• Quantitative PCR was used to measure leukocyte mtDNA content in 299 HEU children and controls.

Main Results:

• The prevalence of ASD among HEU children in this cohort was 4.7%, exceeding general population estimates.
• HEU children without ASD and HUU children with ASD exhibited higher mtDNA content than HUU controls.
• HEU children with ASD demonstrated significantly elevated leukocyte mtDNA content compared to all other groups.

Conclusions:

• Elevated leukocyte mtDNA content is strongly associated with both HIV-exposed, uninfected status and ASD diagnosis.
• Mitochondrial dysfunction may play a role in the increased prevalence of ASD observed in HEU children.
• Further research is warranted to elucidate the mechanisms linking perinatal ART exposure, mitochondrial function, and neurodevelopmental outcomes.