Lack of definitive severe mitochondrial signs and symptoms among deceased HIV-uninfected and HIV-indeterminate children ≤ 5 years of age, pediatric spectrum of HIV disease project (PSD), USA

K. Dominguez, J. Bertolli, M. Fowler, V. Peters, I. Ortiz, S. Melville, T. Rakusan, T. Frederick, H. Hsu, P. D'Almada, Y. Maldonado, C. Wilfert, M. Bulterys, S. K. Burchett, M. Culnane, B. Cunningham-Schrader, L. Dunkle, L. Draper, C. Hanson, E. KpameganM. L. Lindegren, L. Martin-Carpenter, K. McIntosh, J. McNamara, G. McSherry, W. G. Mitchell, L. M. Mofenson, J. M. Oleske, P. Rhodes, D. E. Shapiro, M. E. Smith, B. Styrt

Research output: Contribution to journalArticle

Abstract

Background: In response to recent reports of mitochondrial dysfunction in HIV-uninfected infants exposed to antiretroviral (ARV) prophylaxis, the Perinatal Safety Review Working Group reviewed deaths in five large HIV-exposed perinatal cohorts in the United States to determine if similar cases of severe mitochondrial toxicity could be detected. We describe the results of this review for the PSD cohort. Methods: Hospitalization, clinic and death records for deceased HIV-uninfected and HIV-indeterminate children who were less than 5 years of age were reviewed. Standard definitions were used to classify HIV infection status and the likelihood that signs and symptoms were related to mitochondrial dysfunction. Children were classified as having signs and symptoms that were considered (1) unrelated, (2) unlikely, (3) consistent with, or (4) likely related to mitochondrial disease. SIDS deaths were put into a separate category. Results: 8,465 of 13,125 HIV-exposed children were either HIV-uninfected or HIV-indeterminate. Among the 84 deaths in the subgroup of 8,465 children, 9 were considered in Class 2 (unlikely), 4 were considered in Class 3 (consistent with), and none were considered in Class 4 (likely). 97% of those children who received ARV prophylaxis received zidovudine alone. None of the HIV-uninfected deaths were classified in 2, 3, or 4; and only one of these was exposed to ARV prophylaxis. Among the 3 HIV-indeterminate children who were classifled in 3 (consistent with), 2 had no or unknown ARV exposure before 1994 when use of ZDV prophylaxis became the standard of care. Both HIV-uninfected and HIV-indeterminate children with ARV exposure or unknown exposure had lower mortality rates than children without ARV exposure. Conclusion: Monoprophylaxis with ZDV was not associated with higher death rates in the cohort of 8,465 children or with any findings likely consistent with mitochondrial dysfunction among the 85 deaths. Ongoing monitoring of drug safety in large multi-site prospective cohort studies of HIV-exposed children is essential in the era of highly active antiretroviral therapy.

Original languageEnglish (US)
Pages (from-to)236-246
Number of pages11
JournalAnnals of the New York Academy of Sciences
Volume918
StatePublished - 2000
Externally publishedYes

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Pediatrics
Signs and Symptoms
HIV
Zidovudine
Toxicity
Monitoring
Pharmaceutical Preparations
Indeterminate
AIDS/HIV
Safety
Mitochondrial Diseases
Death Certificates
Sudden Infant Death
Mortality
Drug Monitoring
Highly Active Antiretroviral Therapy
Standard of Care
HIV Infections
Hospitalization
Cohort Studies

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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Lack of definitive severe mitochondrial signs and symptoms among deceased HIV-uninfected and HIV-indeterminate children ≤ 5 years of age, pediatric spectrum of HIV disease project (PSD), USA. / Dominguez, K.; Bertolli, J.; Fowler, M.; Peters, V.; Ortiz, I.; Melville, S.; Rakusan, T.; Frederick, T.; Hsu, H.; D'Almada, P.; Maldonado, Y.; Wilfert, C.; Bulterys, M.; Burchett, S. K.; Culnane, M.; Cunningham-Schrader, B.; Dunkle, L.; Draper, L.; 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.; Shapiro, D. E.; Smith, M. E.; Styrt, B.

In: Annals of the New York Academy of Sciences, Vol. 918, 2000, p. 236-246.

Research output: Contribution to journalArticle

Dominguez, K, Bertolli, J, Fowler, M, Peters, V, Ortiz, I, Melville, S, Rakusan, T, Frederick, T, Hsu, H, D'Almada, P, Maldonado, Y, Wilfert, C, Bulterys, M, Burchett, SK, Culnane, M, Cunningham-Schrader, B, Dunkle, L, Draper, L, 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, 'Lack of definitive severe mitochondrial signs and symptoms among deceased HIV-uninfected and HIV-indeterminate children ≤ 5 years of age, pediatric spectrum of HIV disease project (PSD), USA', Annals of the New York Academy of Sciences, vol. 918, pp. 236-246.
Dominguez, K. ; Bertolli, J. ; Fowler, M. ; Peters, V. ; Ortiz, I. ; Melville, S. ; Rakusan, T. ; Frederick, T. ; Hsu, H. ; D'Almada, P. ; Maldonado, Y. ; Wilfert, C. ; Bulterys, M. ; Burchett, S. K. ; Culnane, M. ; Cunningham-Schrader, B. ; Dunkle, L. ; Draper, L. ; 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. ; Shapiro, D. E. ; Smith, M. E. ; Styrt, B. / Lack of definitive severe mitochondrial signs and symptoms among deceased HIV-uninfected and HIV-indeterminate children ≤ 5 years of age, pediatric spectrum of HIV disease project (PSD), USA. In: Annals of the New York Academy of Sciences. 2000 ; Vol. 918. pp. 236-246.
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title = "Lack of definitive severe mitochondrial signs and symptoms among deceased HIV-uninfected and HIV-indeterminate children ≤ 5 years of age, pediatric spectrum of HIV disease project (PSD), USA",
abstract = "Background: In response to recent reports of mitochondrial dysfunction in HIV-uninfected infants exposed to antiretroviral (ARV) prophylaxis, the Perinatal Safety Review Working Group reviewed deaths in five large HIV-exposed perinatal cohorts in the United States to determine if similar cases of severe mitochondrial toxicity could be detected. We describe the results of this review for the PSD cohort. Methods: Hospitalization, clinic and death records for deceased HIV-uninfected and HIV-indeterminate children who were less than 5 years of age were reviewed. Standard definitions were used to classify HIV infection status and the likelihood that signs and symptoms were related to mitochondrial dysfunction. Children were classified as having signs and symptoms that were considered (1) unrelated, (2) unlikely, (3) consistent with, or (4) likely related to mitochondrial disease. SIDS deaths were put into a separate category. Results: 8,465 of 13,125 HIV-exposed children were either HIV-uninfected or HIV-indeterminate. Among the 84 deaths in the subgroup of 8,465 children, 9 were considered in Class 2 (unlikely), 4 were considered in Class 3 (consistent with), and none were considered in Class 4 (likely). 97{\%} of those children who received ARV prophylaxis received zidovudine alone. None of the HIV-uninfected deaths were classified in 2, 3, or 4; and only one of these was exposed to ARV prophylaxis. Among the 3 HIV-indeterminate children who were classifled in 3 (consistent with), 2 had no or unknown ARV exposure before 1994 when use of ZDV prophylaxis became the standard of care. Both HIV-uninfected and HIV-indeterminate children with ARV exposure or unknown exposure had lower mortality rates than children without ARV exposure. Conclusion: Monoprophylaxis with ZDV was not associated with higher death rates in the cohort of 8,465 children or with any findings likely consistent with mitochondrial dysfunction among the 85 deaths. Ongoing monitoring of drug safety in large multi-site prospective cohort studies of HIV-exposed children is essential in the era of highly active antiretroviral therapy.",
author = "K. Dominguez and J. Bertolli and M. Fowler and V. Peters and I. Ortiz and S. Melville and T. Rakusan and T. Frederick and H. Hsu and P. D'Almada and Y. Maldonado and C. Wilfert and M. Bulterys and Burchett, {S. K.} and M. Culnane and B. Cunningham-Schrader and L. Dunkle and L. Draper and C. Hanson and E. Kpamegan and Lindegren, {M. L.} and L. Martin-Carpenter and K. McIntosh and J. McNamara and G. McSherry and Mitchell, {W. G.} and Mofenson, {L. M.} and Oleske, {J. M.} and P. Rhodes and Shapiro, {D. E.} and Smith, {M. E.} and B. Styrt",
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pages = "236--246",
journal = "Annals of the New York Academy of Sciences",
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TY - JOUR

T1 - Lack of definitive severe mitochondrial signs and symptoms among deceased HIV-uninfected and HIV-indeterminate children ≤ 5 years of age, pediatric spectrum of HIV disease project (PSD), USA

AU - Dominguez, K.

AU - Bertolli, J.

AU - Fowler, M.

AU - Peters, V.

AU - Ortiz, I.

AU - Melville, S.

AU - Rakusan, T.

AU - Frederick, T.

AU - Hsu, H.

AU - D'Almada, P.

AU - Maldonado, Y.

AU - Wilfert, C.

AU - Bulterys, M.

AU - Burchett, S. K.

AU - Culnane, M.

AU - Cunningham-Schrader, B.

AU - Dunkle, L.

AU - Draper, L.

AU - Hanson, C.

AU - Kpamegan, E.

AU - Lindegren, M. L.

AU - Martin-Carpenter, L.

AU - McIntosh, K.

AU - McNamara, J.

AU - McSherry, G.

AU - Mitchell, W. G.

AU - Mofenson, L. M.

AU - Oleske, J. M.

AU - Rhodes, P.

AU - Shapiro, D. E.

AU - Smith, M. E.

AU - Styrt, B.

PY - 2000

Y1 - 2000

N2 - Background: In response to recent reports of mitochondrial dysfunction in HIV-uninfected infants exposed to antiretroviral (ARV) prophylaxis, the Perinatal Safety Review Working Group reviewed deaths in five large HIV-exposed perinatal cohorts in the United States to determine if similar cases of severe mitochondrial toxicity could be detected. We describe the results of this review for the PSD cohort. Methods: Hospitalization, clinic and death records for deceased HIV-uninfected and HIV-indeterminate children who were less than 5 years of age were reviewed. Standard definitions were used to classify HIV infection status and the likelihood that signs and symptoms were related to mitochondrial dysfunction. Children were classified as having signs and symptoms that were considered (1) unrelated, (2) unlikely, (3) consistent with, or (4) likely related to mitochondrial disease. SIDS deaths were put into a separate category. Results: 8,465 of 13,125 HIV-exposed children were either HIV-uninfected or HIV-indeterminate. Among the 84 deaths in the subgroup of 8,465 children, 9 were considered in Class 2 (unlikely), 4 were considered in Class 3 (consistent with), and none were considered in Class 4 (likely). 97% of those children who received ARV prophylaxis received zidovudine alone. None of the HIV-uninfected deaths were classified in 2, 3, or 4; and only one of these was exposed to ARV prophylaxis. Among the 3 HIV-indeterminate children who were classifled in 3 (consistent with), 2 had no or unknown ARV exposure before 1994 when use of ZDV prophylaxis became the standard of care. Both HIV-uninfected and HIV-indeterminate children with ARV exposure or unknown exposure had lower mortality rates than children without ARV exposure. Conclusion: Monoprophylaxis with ZDV was not associated with higher death rates in the cohort of 8,465 children or with any findings likely consistent with mitochondrial dysfunction among the 85 deaths. Ongoing monitoring of drug safety in large multi-site prospective cohort studies of HIV-exposed children is essential in the era of highly active antiretroviral therapy.

AB - Background: In response to recent reports of mitochondrial dysfunction in HIV-uninfected infants exposed to antiretroviral (ARV) prophylaxis, the Perinatal Safety Review Working Group reviewed deaths in five large HIV-exposed perinatal cohorts in the United States to determine if similar cases of severe mitochondrial toxicity could be detected. We describe the results of this review for the PSD cohort. Methods: Hospitalization, clinic and death records for deceased HIV-uninfected and HIV-indeterminate children who were less than 5 years of age were reviewed. Standard definitions were used to classify HIV infection status and the likelihood that signs and symptoms were related to mitochondrial dysfunction. Children were classified as having signs and symptoms that were considered (1) unrelated, (2) unlikely, (3) consistent with, or (4) likely related to mitochondrial disease. SIDS deaths were put into a separate category. Results: 8,465 of 13,125 HIV-exposed children were either HIV-uninfected or HIV-indeterminate. Among the 84 deaths in the subgroup of 8,465 children, 9 were considered in Class 2 (unlikely), 4 were considered in Class 3 (consistent with), and none were considered in Class 4 (likely). 97% of those children who received ARV prophylaxis received zidovudine alone. None of the HIV-uninfected deaths were classified in 2, 3, or 4; and only one of these was exposed to ARV prophylaxis. Among the 3 HIV-indeterminate children who were classifled in 3 (consistent with), 2 had no or unknown ARV exposure before 1994 when use of ZDV prophylaxis became the standard of care. Both HIV-uninfected and HIV-indeterminate children with ARV exposure or unknown exposure had lower mortality rates than children without ARV exposure. Conclusion: Monoprophylaxis with ZDV was not associated with higher death rates in the cohort of 8,465 children or with any findings likely consistent with mitochondrial dysfunction among the 85 deaths. Ongoing monitoring of drug safety in large multi-site prospective cohort studies of HIV-exposed children is essential in the era of highly active antiretroviral therapy.

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