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 Citations (Scopus)

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

Fingerprint

Mitochondrial Diseases
Nucleosides
HIV
Sudden Infant Death
Reverse Transcriptase Inhibitors
Pharmaceutical Preparations
Hospital Laboratories
Reproductive History
Autopsy
Physicians

All Science Journal Classification (ASJC) codes

  • Infectious Diseases
  • Pharmacology (medical)

Keywords

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

Cite this

Bulterys, Marc ; Burchett, Sandra K. ; Culnane, Mary ; Cunningham-Schrader, Bethann ; Dominguez, Ken ; Dunkle, Lisa ; Draper, Linda ; Fowler, Mary Glenn ; Hanson, Celine ; Kpamegan, Eloi ; Lindegren, Mary Lou ; Martin-Carpenter, Louise ; McIntosh, Kenneth ; McNamara, James ; McSherry, George ; Mitchell, Wendy G. ; Mofenson, Lynne M. ; Oleske, James M. ; Rhodes, Phillip ; Shapiro, David E. ; Smith, Mary E. ; Styrt, Barbara. / 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. In: Journal of Acquired Immune Deficiency Syndromes. 2000 ; Vol. 25, No. 3. pp. 261-268.
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title = "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",
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.",
keywords = "Antiretroviral drugs, HIV, Infants, Mitochondrial dysfunction, Mothers",
author = "Marc Bulterys and Burchett, {Sandra K.} and Mary Culnane and Bethann Cunningham-Schrader and Ken Dominguez and Lisa Dunkle and Linda Draper and Fowler, {Mary Glenn} and Celine Hanson and Eloi Kpamegan and Lindegren, {Mary Lou} and Louise Martin-Carpenter and Kenneth McIntosh and James McNamara and George McSherry and Mitchell, {Wendy G.} and Mofenson, {Lynne M.} and Oleske, {James M.} and Phillip Rhodes and Shapiro, {David E.} and Smith, {Mary E.} and Barbara Styrt",
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Bulterys, M, Burchett, SK, Culnane, M, Cunningham-Schrader, B, Dominguez, K, Dunkle, L, Draper, L, Fowler, MG, Hanson, C, Kpamegan, E, Lindegren, ML, Martin-Carpenter, L, McIntosh, K, McNamara, J, McSherry, G, Mitchell, WG, Mofenson, LM, Oleske, JM, Rhodes, P, Shapiro, DE, Smith, ME & 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, vol. 25, no. 3, pp. 261-268. https://doi.org/10.1097/00126334-200011010-00009

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

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 25, No. 3, 01.11.2000, p. 261-268.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Nucleoside exposure in the children of HIV-infected women receiving antiretroviral drugs

T2 - Absence of clear evidence for mitochondrial disease in children who died before 5 years of age in five United States cohorts

AU - Bulterys, Marc

AU - Burchett, Sandra K.

AU - Culnane, Mary

AU - Cunningham-Schrader, Bethann

AU - Dominguez, Ken

AU - Dunkle, Lisa

AU - Draper, Linda

AU - Fowler, Mary Glenn

AU - Hanson, Celine

AU - Kpamegan, Eloi

AU - Lindegren, Mary Lou

AU - Martin-Carpenter, Louise

AU - McIntosh, Kenneth

AU - McNamara, James

AU - McSherry, George

AU - Mitchell, Wendy G.

AU - Mofenson, Lynne M.

AU - Oleske, James M.

AU - Rhodes, Phillip

AU - Shapiro, David E.

AU - Smith, Mary E.

AU - Styrt, Barbara

PY - 2000/11/1

Y1 - 2000/11/1

N2 - 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.

AB - 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.

KW - Antiretroviral drugs

KW - HIV

KW - Infants

KW - Mitochondrial dysfunction

KW - Mothers

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