Nucleoside exposure in the children of HIV-infected women receiving antiretroviral drugs: Absence of clear evidence for mitochondrial disease in children who died before 5 years of age in five United States cohorts

Marc Bulterys, Sandra K. Burchett, Mary Culnane, Bethann Cunningham-Schrader, Ken Dominguez, Lisa Dunkle, Linda Draper, Mary Glenn Fowler, Celine Hanson, Eloi Kpamegan, Mary Lou Lindegren, Louise Martin-Carpenter, Kenneth McIntosh, James McNamara, George McSherry, Wendy G. Mitchell, Lynne M. Mofenson, James M. Oleske, Phillip Rhodes, David E. ShapiroMary E. Smith, Barbara Styrt

Research output: Contribution to journalArticle

140 Scopus citations

Abstract

Background: Nucleoside reverse transcriptase inhibitors (NRTIs) have been associated with mitochondrial toxicity in individuals receiving treatment. A report of two deaths in Europe attributed to mitochondrial dysfunction in HIV-uninfected infants with perinatal NRTI exposure prompted a review of five U.S. cohorts. Methods: Deaths in HIV-exposed children <60 months of age and HIV-uninfected or indeterminate were reviewed. Review included birth history; perinatal antiretroviral drug exposure; hospital, laboratory, and clinic records; death reports; autopsy results; and local physician queries. Deaths were classified as unrelated (Class 1), unlikely related (Class 2), possibly related (Class 3), or highly suggestive or proven relationship (Class 4), to mitochondrial dysfunction; sudden infant death syndrome (SIDS) was categorized separately. Results and Conclusions: Among over 20,000 children of HIV-infected women, over half of whom had been exposed to NRTIs, 223 died. In HIV-uninfected children, 26 deaths were attributed to Class 1, and 4 were attributed to SIDS. In HIV-indeterminate children, 141, 10, 3, and 0 were Classes 1, 2, 3, and 4, respectively; 33 were due to SIDS and 6 could not be classified. There was no indication that antiretroviral exposure was associated with Class 2 or 3 deaths, or deaths from SIDS. A search for mitochondrial dysfunction among living children in these cohorts is ongoing.

Original languageEnglish (US)
Pages (from-to)261-268
Number of pages8
JournalJournal of Acquired Immune Deficiency Syndromes
Volume25
Issue number3
DOIs
StatePublished - Nov 1 2000

All Science Journal Classification (ASJC) codes

  • Infectious Diseases
  • Pharmacology (medical)

Keywords

  • Antiretroviral drugs
  • HIV
  • Infants
  • Mitochondrial dysfunction
  • Mothers

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    Bulterys, M., Burchett, S. K., Culnane, M., Cunningham-Schrader, B., Dominguez, K., Dunkle, L., Draper, L., Fowler, M. G., Hanson, C., Kpamegan, E., Lindegren, M. L., Martin-Carpenter, L., McIntosh, K., McNamara, J., McSherry, G., Mitchell, W. G., Mofenson, L. M., Oleske, J. M., Rhodes, P., ... Styrt, B. (2000). Nucleoside exposure in the children of HIV-infected women receiving antiretroviral drugs: Absence of clear evidence for mitochondrial disease in children who died before 5 years of age in five United States cohorts. Journal of Acquired Immune Deficiency Syndromes, 25(3), 261-268. https://doi.org/10.1097/00126334-200011010-00009