Long-Term Persistence of Mitochondrial DNA Instability in HIV-Exposed Uninfected Children during and after Exposure to Antiretroviral Drugs and HIV
Valérie Desquiret-Dumas,
Morgana D’Ottavi,
Audrey Monnin,
David Goudenège,
Nicolas Méda,
Amélie Vizeneux,
Chipepo Kankasa,
Thorkild Tylleskar,
Céline Bris,
Vincent Procaccio,
Nicolas Nagot,
Philippe Van de Perre,
Pascal Reynier,
Jean-Pierre Molès
Affiliations
Valérie Desquiret-Dumas
Department of Biochemistry and Genetics, University Hospital of Angers, F-49000 Angers, France
Morgana D’Ottavi
Pathogenesis and Control of Chronic and Emerging Infections, INSERM, Etablissement Français du Sang, University of Montpellier, University of Antilles, F-34394 Montpellier, France
Audrey Monnin
Pathogenesis and Control of Chronic and Emerging Infections, INSERM, Etablissement Français du Sang, University of Montpellier, University of Antilles, F-34394 Montpellier, France
David Goudenège
Department of Biochemistry and Genetics, University Hospital of Angers, F-49000 Angers, France
Nicolas Méda
Centre MURAZ, Bobo-Dioulasso 01 B.P. 390, Burkina Faso
Amélie Vizeneux
Pathogenesis and Control of Chronic and Emerging Infections, INSERM, Etablissement Français du Sang, University of Montpellier, University of Antilles, F-34394 Montpellier, France
Chipepo Kankasa
Department of Paediatrics and Child Health, University Teaching Hospital, Lusaka P.O. Box 50001, Zambia
Thorkild Tylleskar
Centre for International Health, University of Bergen, N-5020 Bergen, Norway
Céline Bris
Department of Biochemistry and Genetics, University Hospital of Angers, F-49000 Angers, France
Vincent Procaccio
Department of Biochemistry and Genetics, University Hospital of Angers, F-49000 Angers, France
Nicolas Nagot
Pathogenesis and Control of Chronic and Emerging Infections, INSERM, Etablissement Français du Sang, University of Montpellier, University of Antilles, F-34394 Montpellier, France
Philippe Van de Perre
Pathogenesis and Control of Chronic and Emerging Infections, INSERM, Etablissement Français du Sang, University of Montpellier, University of Antilles, F-34394 Montpellier, France
Pascal Reynier
Department of Biochemistry and Genetics, University Hospital of Angers, F-49000 Angers, France
Jean-Pierre Molès
Pathogenesis and Control of Chronic and Emerging Infections, INSERM, Etablissement Français du Sang, University of Montpellier, University of Antilles, F-34394 Montpellier, France
HIV-exposed uninfected (HEU) children show impaired health outcomes during childhood. A high rate of mitochondrial DNA (mtDNA) instability was reported in the blood of HEU at birth. We aimed to explore the relationship between these health outcomes and mtDNA deletions over time in a case series of 24 HEU children. MtDNA instability was assessed by deep sequencing and analyzed by eKLIPse-v2 algorithm at three time points, namely birth, 1 year, and 6 years of age. Association between mtDNA deletion and health outcomes, including growth, clinical, and neurodevelopmental parameters, were explored using univariate statistical analyses and after stratification with relevant variables. HEU children were selected with an equal male:female ratio. An elevated number of mtDNA deletions and duplications events was observed at 7 days’ post-partum. Median heteroplasmy increased at one year of life and then returned to baseline by six years of age. The mtDNA instability was acquired and was not transmitted by the mother. No risk factors were significantly associated with mtDNA instability. In this small case series, we did not detect any association between any health outcome at 6 years and mtDNA instability measures. A significant effect modification of the association between the duration of maternal prophylaxis and child growth was observed after stratification with heteroplasmy rate. Genomic instability persists over time among HEU children but, despite its extension, stays subclinical at six years.
