Published online October 18, 2004
PEDIATRICS Vol. 114 No. 5 November 2004, pp. e598-e603 (doi:10.1542/peds.2004-0955)
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ELECTRONIC ARTICLE

Hyperlactatemia in Human Immunodeficiency Virus–Uninfected Infants Who Are Exposed to Antiretrovirals

Antoni Noguera, MD*, Claudia Fortuny, MD, PhD*, Carmen Muñoz-Almagro, MD{ddagger}, Emilia Sanchez, MD, PhD§, M. Antonia Vilaseca, PhD{ddagger}, Rafael Artuch, MD, PhD{ddagger}, Jordi Pou, MD, PhD* and Rafael Jimenez, MD, PhD*

* Infectious Diseases Unit, Pediatrics Department, Integrated Unit Hospital Sant Joan de Déu, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain
{ddagger} Laboratory Department, Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain
§ Catalan Agency for Health Technology Assessment and Research, Catalan Health Service, Department of Health and Social Security, Generalitat de Catalunya, Barcelona, Spain

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.

Key Words: alanine • children • HAART • HIV infection • hyperlactatemia • mitochondria • vertical transmission

Abbreviations: HIV, human immunodeficiency virus • ARV, antiretroviral • NRTI, nucleoside analogue reverse transcriptase inhibitor • LA, lactate • HLA, hyperlactatemia • HCV, hepatitis C virus • HBV, hepatitis B virus • ZDV, zidovudine • HAART, highly active antiretroviral therapy • 3TC, lamivudine • d4T, stavudine • NVP, nevirapine • NFV, nelfinavir • ddI, didanosine

Accepted Jun 8, 2004.