Persistent mitochondrial dysfunction in HIV-1-exposed but uninfected infants: clinical screening in a large prospective cohort.
BACKGROUND
Antiretroviral prevention of mother to child HIV-1 is established but tolerance remains to be assessed. AIM To determine the risk for persistent mitochondrial dysfunction in HIV-uninfected children born to seropositive mothers.


METHODS
An exhaustive study in a large prospective cohort with predetermined algorithm of the unexplained symptoms compatible with mitochondrial dysfunction. A total of 2644 of 4392 children were exposed to antiretrovirals. Complementary investigations were carried out on a case-by-case basis using classification with a diagnostic probability scale, based on experience with constitutional diseases. A spontaneous notification register for children not included in the cohort was created.


RESULTS
Good circumstantial evidence of mitochondrial dysfunction was found for twelve children. Seven were from the cohort. All presented neurological symptoms, often associated with abnormal magnetic resonance image (10 of 12) and/or a significant episode of hyperlactatemia (seven of 12). All had either a profound deficit in one of the respiratory chain complexes (11 of 12) and/or a typical histological pattern (two of 12). All were perinatally exposed to antiretrovirals. None of them had perinatal morbidity that could explain this symptomatology. The 18-month incidence was 0.26% (95% confidence interval, 0.10-0.54) in exposed children, in comparison with the general figure of 0.01% for paediatric neuro-mitochondrial diseases in the general population. Fourteen other children in the cohort, all exposed to antiretrovirals, had unexplained symptoms, mostly neurological, for which one of the possible differential diagnoses was mitochondrial dysfunction. Close similarities in clinical, neuroradiological and histological findings strongly suggest a common pathological process in all these 26 children.


CONCLUSIONS
Children exposed to nucleoside analogues during the perinatal period are at risk of a neurological syndrome associated with persistent mitochondrial dysfunction.
Barret
Béatrice
B
INSERM U569 (Epidémiologie, Démographie et Sciences Sociales) Hôpital Bicêtre AP-HP, Le Kremlin Bicêtre, France.
Tardieu
Marc
M
Rustin
Pierre
P
Lacroix
Catherine
C
Chabrol
Brigitte
B
Desguerre
Isabelle
I
Dollfus
Catherine
C
Mayaux
Marie-Jeanne
MJ
Blanche
Stéphane
S
D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001921:Brain / Q000473:pathology; D016009:Chi-Square Distribution; D005260:Female; D015658:HIV Infections / Q000517:prevention & control* / Q000635:transmission; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D008279:Magnetic Resonance Imaging; D008854:Microscopy, Electron; D008931:Mitochondria, Muscle / Q000648:ultrastructure; D028361:Mitochondrial Diseases / Q000175:diagnosis / Q000209:etiology* / Q000473:pathology; D018482:Muscle, Skeletal / Q000201:enzymology; D011247:Pregnancy; D011446:Prospective Studies; D012307:Risk Factors; D015215:Zidovudine / Q000009:adverse effects* / Q000627:therapeutic use
D019380:Anti-HIV Agents; D015215:Zidovudine