title: Hyperlactatemia in human immunodeficiency virus-uninfected infants who are exposed to antiretrovirals.
abstract: OBJECTIVE
  Exposure to nucleoside analogues in fetal or early life has been associated with rare clinically significant mitochondrial toxic effects, mainly neurologic symptoms. Lactate (LA) measurements have been used to monitor nucleoside-related mitochondrial toxicity. Our aim was to determine the prevalence, clinical evolution, and risk factors for hyperlactatemia in our cohort of human immunodeficiency virus (HIV)-uninfected children who were exposed to antiretrovirals.
  
  
  METHODS
  We conducted a prospective observational study of 127 HIV-uninfected infants who were born to HIV-infected women. Clinical symptoms suggesting mitochondrial dysfunction were analyzed in routine follow-up, and LA and alanine plasma levels were obtained at 6 weeks, 3 months, 6 months, and 12 months in all patients. Elevated alanine levels, together with hyperlactatemia, suggest chronic mitochondrial injury.
  
  
  RESULTS
  Most (85%) women received highly active antiretroviral therapy (HAART) during pregnancy (mean duration: 31 weeks) and zidovudine during labor (93%). Most (96%) children received zidovudine alone. Hyperlactatemia with hyperalaninemia was detected in 63 children in at least 1 of the measurements. Mean LA levels were significantly higher in children who were exposed to nucleoside analogue reverse transcriptase inhibitors than in control subjects (2.88 vs 1.61 at 6 weeks, 2.78 vs 1.49 at 3 months, 1.89 vs 1.39 at 6 months, and 1.71 vs 1.24 at 12 months; peak levels: 8.06, 10.1, 7.28, and 4.48 mmol/L, respectively). In 44 patients, LA levels progressed spontaneously to normality within the first year of life. Three girls presented a slight and self-limited delay in psychomotor development, with LA peak levels of 7.3, 4.0, and 4.6 mmol/L. Only the gestational use of didanosine was associated with a higher risk of hyperlactatemia.
  
  
  CONCLUSIONS
  In our series, almost half of the children (63 of 127) who were exposed to nucleoside analogues developed benign and self-limited hyperlactatemia. When symptomatic, nucleoside analogue-induced toxicity affected neurologic development.
authors.affiliation: Infectious Diseases Unit, Pediatrics Department, Integrated Unit Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Noguera
authors.forename: Claudia
authors.initials: C
authors.lastname: Fortuny
authors.forename: Carmen
authors.initials: C
authors.lastname: Muñoz-Almagro
authors.forename: Emilia
authors.initials: E
authors.lastname: Sanchez
authors.forename: M Antonia
authors.initials: MA
authors.lastname: Vilaseca
authors.forename: Rafael
authors.initials: R
authors.lastname: Artuch
authors.forename: Jordi
authors.initials: J
authors.lastname: Pou
authors.forename: Rafael
authors.initials: R
authors.lastname: Jimenez
mesh_terms: D000409:Alanine / Q000097:blood; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D016049:Didanosine / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D015658:HIV Infections / Q000188:drug therapy; D018023:HIV Seronegativity; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D019344:Lactic Acid; D016015:Logistic Models; D008297:Male; D008928:Mitochondria / Q000187:drug effects*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D015215:Zidovudine / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D018894:Reverse Transcriptase Inhibitors; D019344:Lactic Acid; D015215:Zidovudine; D016049:Didanosine; D000409:Alanine