Lactic acidemia in human immunodeficiency virus-uninfected infants exposed to perinatal antiretroviral therapy

OBJECTIVE: To investigate potential mitochondrial toxicity in HIV-uninfected infants exposed to highly active antiretroviral therapy (HAART) in utero and/or neonatal zidovudine. DESIGN: A prospective observational study performed in a tertiary referral center for HIV-infected women and their infants and children. METHODS: Plasma lactate was measured repeatedly during the first 6 months of life in a consecutive cohort of infants exposed to HAART in utero and/or neonatal zidovudine. Maternal CD4, HIV RNA concentration, antiretroviral and substance use histories, mode of delivery, infant gender, cord pH, Apgar score and birth weight were collected. RESULTS: The plasma lactate was above normal on at least 1 occasion in 35 of 38 (92%) infants and reached levels > or =5 mmol/l in 10 (26%) infants. Overall 78 of 117 (68%) lactate measurements were elevated, with 11 (10%) in the serious (> or =5 mmol/l) range. None of the infants received antiretrovirals beyond 6 weeks, yet elevated lactates persisted up to age 6 months. Two infants had reversible symptoms consistent with those of lactic acidemia. No association was found between the infant peak lactate and the type of therapy during pregnancy, its duration or maternal substance use. CONCLUSION: Transient lactic acidemia was observed in the majority of HIV uninfected infants exposed to HAART in utero and/or zidovudine neonatally. We hypothesize that the hyperlactatemia is a consequence of persistent, primarily subclinical, mitochondrial toxicity from the transplacental and neonatal exposure to antiretrovirals and of impaired hepatic lactate clearance. Although the clinical relevance of our findings is unknown, we recommend lactate monitoring in these infants, considering discontinuation of neonatal zidovudine in symptomatic infants with lactate > or =5 mmol/l and careful long term follow up of these children.