Clinical mitochondrial dysfunction in uninfected children born to HIV-infected mothers following perinatal exposure to nucleoside analogues.
Clinical and biological observations of mitochondrial dysfunction in children exposed to zidovudine (azidothymidine, AZT) during the perinatal period rapidly followed similar observations in animal experiments. To date, two different disorders have been identified. The first, asymptomatic hyperlactatemia, is observed during treatment in one third of exposed newborns, and is reversible with treatment cessation. In rare cases, it is associated with symptomatic acidosis. Regression may be slow, taking up to several months after the end of the treatment. The long-term clinical consequences of this biochemical disturbance are unknown. The second disorder involves severe neurological symptoms, which become clinically detectable during the first 2 years of life. These symptoms are associated with a series of biochemical and ultrastructural changes consistent with persistent mitochondrial dysfunction. This latter phenomenon is rare, and affects only 0.3-0.5% of exposed children in the French pediatric cohort, in which observations continue. Despite initial controversy, several similar observations in other cohorts have since confirmed its occurrence. The pathophysiology of these two mitochondrial dysfunctions may differ. Continued efforts to identify and understand clinical mitochondrial toxicities are essential, given the intensification and diversification of perinatal prophylaxis strategies, and the number of pregnant women potentially involved.
Benhammou
Valérie
V
INSERM U569 Epidémiologie et Reproduction, Hôpital Bicêtre, Kremlin Bicêtre, France.
Tardieu
Marc
M
Warszawski
Josiane
J
Rustin
Pierre
P
Blanche
Stéphane
S
D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000517:prevention & control*; D006801:Humans; D028361:Mitochondrial Diseases / Q000139:chemically induced* / Q000453:epidemiology; D009035:Mothers; D009705:Nucleosides / Q000009:adverse effects* / Q000627:therapeutic use; D011247:Pregnancy; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use
D019380:Anti-HIV Agents; D009705:Nucleosides; D018894:Reverse Transcriptase Inhibitors