Cardiac effects of in-utero exposure to antiretroviral therapy in HIV-uninfected children born to HIV-infected mothers

Steven E. Lipshultz, Paige L. Williams, Bret Zeldow, James D. Wilkinson, Kenneth C. Rich, Russell B. Van Dyke, George R. Seage, Laurie B. Dooley, Jonathan R. Kaltman, George K. Siberry, Lynne M. Mofenson, William T. Shearer, Steven D. Colan, Mary Paul, Norma Cooper, Lynette Harris, Murli Purswani, Emma Stuard, Anna Cintron, Ana Puga & 58 others Dia Cooley, Doyle Patton, Deyana Leon, Richard Rutstein, Carol Vincent, Nancy Silverman, Ram Yogev, Margaret Ann Sanders, Kathleen Malee, Scott Hunter, Andrew Wiznia, Marlene Burey, Molly Nozyce, William Borkowsky, Sandra Deygoo, Helen Rozelman, Katherine Knapp, Kim Allison, Megan Wilkins, Midnela Acevedo-Flores, Lourdes Angeli-Nieves, Vivian Olivera, Hermann Mendez, Ava Dennie, Susan Bewley, Sharon Nachman, Margaret Oliver, Karen Craig, Patricia Sirois, Marilyn Crain, Newana Beatty, Dan Marullo, Stephen Spector, Jean Manning, Sharon Nichols, Elizabeth McFarland, Emily Barr, Robin McEvoy, Mobeen Rathore, Kristi Stowers, Ann Usitalo, Delmyra Turpin, Renee Smith, Douglas Watson, Latoya Stubbs, Rose Belanger, Arry Dieudonne, Linda Bettica, Susan Adubato, Gwendolyn Scott, Claudia Florez, Elizabeth Willen, Toinette Frederick, Mariam Davtyan, Maribel Mejia, Zoe Rodriguez, Ibet Heyer, Nydia Scalley Trifilio

Research output: Contribution to journalArticle

Abstract

Objectives: We evaluated the potential cardiac effects of in-utero exposures to antiretroviral drugs in HIV-exposed but uninfected (HEU) children. Design and methods: We compared echocardiographic parameters of left ventricular function (ejection fraction, fractional shortening, and stress-velocity index) and structure (left ventricular dimension, posterior wall/septal thickness, mass, thickness-todimension ratio, and wall stress) (expressed as Z-scores to account for age and body surface area) between HEU and HIV-unexposed cohorts from the Pediatric HIV/AIDS Cohort Study's Surveillance Monitoring for ART Toxicities study. Within the HEU group, we investigated the associations between the echocardiographic Z-scores and in-utero exposures to maternal antiretroviral drugs . Results: There were no significant differences in echocardiographic Z-scores between 417HEUand 98 HIV-unexposed children aged 2-7 years. Restricting the analysis toHEU children, first-trimester exposures to combination antiretroviral therapy (a regimen including at least three antiretroviral drugs) and to certain specific antiretroviral drugs were associated with significantly lower stress-velocity Z-scores (mean decreases of 0.22-0.40 SDs). Exposure to combination antiretroviral therapy was also associated with lower left ventricular dimension Z-scores (mean decrease of 0.44 SD). First-trimester exposure to combination antiretroviral therapy was associated with higher mean left ventricular posterior wall thickness and lower mean left ventricular wall stress Z-scores . Conclusion: There was no evidence of significant cardiac toxicity of perinatal combination antiretroviral therapy exposure in HEU children. Subclinical differences in left ventricular structure and function with specific in-utero antiretroviral exposures indicate the need for a longitudinal cardiac study in HEU children to assess long-term cardiac risk and cardiac monitoring recommendations .

Original languageEnglish (US)
Pages (from-to)91-100
Number of pages10
JournalAIDS
Volume29
Issue number1
DOIs
StatePublished - 2015
Externally publishedYes

Fingerprint

Mothers
HIV
First Pregnancy Trimester
Therapeutics
Left Ventricular Function
Pharmaceutical Preparations
Implosive Therapy
Maternal Exposure
Body Surface Area
Stroke Volume
Longitudinal Studies
Acquired Immunodeficiency Syndrome
Cohort Studies
Pediatrics

Keywords

  • Antiretroviral drugs
  • Cardiac
  • HIV
  • Pediatrics
  • Toxicity

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Lipshultz, S. E., Williams, P. L., Zeldow, B., Wilkinson, J. D., Rich, K. C., Van Dyke, R. B., ... Trifilio, N. S. (2015). Cardiac effects of in-utero exposure to antiretroviral therapy in HIV-uninfected children born to HIV-infected mothers. AIDS, 29(1), 91-100. https://doi.org/10.1097/QAD.0000000000000499

Cardiac effects of in-utero exposure to antiretroviral therapy in HIV-uninfected children born to HIV-infected mothers. / Lipshultz, Steven E.; Williams, Paige L.; Zeldow, Bret; Wilkinson, James D.; Rich, Kenneth C.; Van Dyke, Russell B.; Seage, George R.; Dooley, Laurie B.; Kaltman, Jonathan R.; Siberry, George K.; Mofenson, Lynne M.; Shearer, William T.; Colan, Steven D.; Paul, Mary; Cooper, Norma; Harris, Lynette; Purswani, Murli; Stuard, Emma; Cintron, Anna; Puga, Ana; Cooley, Dia; Patton, Doyle; Leon, Deyana; Rutstein, Richard; Vincent, Carol; Silverman, Nancy; Yogev, Ram; Sanders, Margaret Ann; Malee, Kathleen; Hunter, Scott; Wiznia, Andrew; Burey, Marlene; Nozyce, Molly; Borkowsky, William; Deygoo, Sandra; Rozelman, Helen; Knapp, Katherine; Allison, Kim; Wilkins, Megan; Acevedo-Flores, Midnela; Angeli-Nieves, Lourdes; Olivera, Vivian; Mendez, Hermann; Dennie, Ava; Bewley, Susan; Nachman, Sharon; Oliver, Margaret; Craig, Karen; Sirois, Patricia; Crain, Marilyn; Beatty, Newana; Marullo, Dan; Spector, Stephen; Manning, Jean; Nichols, Sharon; McFarland, Elizabeth; Barr, Emily; McEvoy, Robin; Rathore, Mobeen; Stowers, Kristi; Usitalo, Ann; Turpin, Delmyra; Smith, Renee; Watson, Douglas; Stubbs, Latoya; Belanger, Rose; Dieudonne, Arry; Bettica, Linda; Adubato, Susan; Scott, Gwendolyn; Florez, Claudia; Willen, Elizabeth; Frederick, Toinette; Davtyan, Mariam; Mejia, Maribel; Rodriguez, Zoe; Heyer, Ibet; Trifilio, Nydia Scalley.

In: AIDS, Vol. 29, No. 1, 2015, p. 91-100.

Research output: Contribution to journalArticle

Lipshultz, SE, Williams, PL, Zeldow, B, Wilkinson, JD, Rich, KC, Van Dyke, RB, Seage, GR, Dooley, LB, Kaltman, JR, Siberry, GK, Mofenson, LM, Shearer, WT, Colan, SD, Paul, M, Cooper, N, Harris, L, Purswani, M, Stuard, E, Cintron, A, Puga, A, Cooley, D, Patton, D, Leon, D, Rutstein, R, Vincent, C, Silverman, N, Yogev, R, Sanders, MA, Malee, K, Hunter, S, Wiznia, A, Burey, M, Nozyce, M, Borkowsky, W, Deygoo, S, Rozelman, H, Knapp, K, Allison, K, Wilkins, M, Acevedo-Flores, M, Angeli-Nieves, L, Olivera, V, Mendez, H, Dennie, A, Bewley, S, Nachman, S, Oliver, M, Craig, K, Sirois, P, Crain, M, Beatty, N, Marullo, D, Spector, S, Manning, J, Nichols, S, McFarland, E, Barr, E, McEvoy, R, Rathore, M, Stowers, K, Usitalo, A, Turpin, D, Smith, R, Watson, D, Stubbs, L, Belanger, R, Dieudonne, A, Bettica, L, Adubato, S, Scott, G, Florez, C, Willen, E, Frederick, T, Davtyan, M, Mejia, M, Rodriguez, Z, Heyer, I & Trifilio, NS 2015, 'Cardiac effects of in-utero exposure to antiretroviral therapy in HIV-uninfected children born to HIV-infected mothers', AIDS, vol. 29, no. 1, pp. 91-100. https://doi.org/10.1097/QAD.0000000000000499
Lipshultz, Steven E. ; Williams, Paige L. ; Zeldow, Bret ; Wilkinson, James D. ; Rich, Kenneth C. ; Van Dyke, Russell B. ; Seage, George R. ; Dooley, Laurie B. ; Kaltman, Jonathan R. ; Siberry, George K. ; Mofenson, Lynne M. ; Shearer, William T. ; Colan, Steven D. ; Paul, Mary ; Cooper, Norma ; Harris, Lynette ; Purswani, Murli ; Stuard, Emma ; Cintron, Anna ; Puga, Ana ; Cooley, Dia ; Patton, Doyle ; Leon, Deyana ; Rutstein, Richard ; Vincent, Carol ; Silverman, Nancy ; Yogev, Ram ; Sanders, Margaret Ann ; Malee, Kathleen ; Hunter, Scott ; Wiznia, Andrew ; Burey, Marlene ; Nozyce, Molly ; Borkowsky, William ; Deygoo, Sandra ; Rozelman, Helen ; Knapp, Katherine ; Allison, Kim ; Wilkins, Megan ; Acevedo-Flores, Midnela ; Angeli-Nieves, Lourdes ; Olivera, Vivian ; Mendez, Hermann ; Dennie, Ava ; Bewley, Susan ; Nachman, Sharon ; Oliver, Margaret ; Craig, Karen ; Sirois, Patricia ; Crain, Marilyn ; Beatty, Newana ; Marullo, Dan ; Spector, Stephen ; Manning, Jean ; Nichols, Sharon ; McFarland, Elizabeth ; Barr, Emily ; McEvoy, Robin ; Rathore, Mobeen ; Stowers, Kristi ; Usitalo, Ann ; Turpin, Delmyra ; Smith, Renee ; Watson, Douglas ; Stubbs, Latoya ; Belanger, Rose ; Dieudonne, Arry ; Bettica, Linda ; Adubato, Susan ; Scott, Gwendolyn ; Florez, Claudia ; Willen, Elizabeth ; Frederick, Toinette ; Davtyan, Mariam ; Mejia, Maribel ; Rodriguez, Zoe ; Heyer, Ibet ; Trifilio, Nydia Scalley. / Cardiac effects of in-utero exposure to antiretroviral therapy in HIV-uninfected children born to HIV-infected mothers. In: AIDS. 2015 ; Vol. 29, No. 1. pp. 91-100.
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T1 - Cardiac effects of in-utero exposure to antiretroviral therapy in HIV-uninfected children born to HIV-infected mothers

AU - Lipshultz, Steven E.

AU - Williams, Paige L.

AU - Zeldow, Bret

AU - Wilkinson, James D.

AU - Rich, Kenneth C.

AU - Van Dyke, Russell B.

AU - Seage, George R.

AU - Dooley, Laurie B.

AU - Kaltman, Jonathan R.

AU - Siberry, George K.

AU - Mofenson, Lynne M.

AU - Shearer, William T.

AU - Colan, Steven D.

AU - Paul, Mary

AU - Cooper, Norma

AU - Harris, Lynette

AU - Purswani, Murli

AU - Stuard, Emma

AU - Cintron, Anna

AU - Puga, Ana

AU - Cooley, Dia

AU - Patton, Doyle

AU - Leon, Deyana

AU - Rutstein, Richard

AU - Vincent, Carol

AU - Silverman, Nancy

AU - Yogev, Ram

AU - Sanders, Margaret Ann

AU - Malee, Kathleen

AU - Hunter, Scott

AU - Wiznia, Andrew

AU - Burey, Marlene

AU - Nozyce, Molly

AU - Borkowsky, William

AU - Deygoo, Sandra

AU - Rozelman, Helen

AU - Knapp, Katherine

AU - Allison, Kim

AU - Wilkins, Megan

AU - Acevedo-Flores, Midnela

AU - Angeli-Nieves, Lourdes

AU - Olivera, Vivian

AU - Mendez, Hermann

AU - Dennie, Ava

AU - Bewley, Susan

AU - Nachman, Sharon

AU - Oliver, Margaret

AU - Craig, Karen

AU - Sirois, Patricia

AU - Crain, Marilyn

AU - Beatty, Newana

AU - Marullo, Dan

AU - Spector, Stephen

AU - Manning, Jean

AU - Nichols, Sharon

AU - McFarland, Elizabeth

AU - Barr, Emily

AU - McEvoy, Robin

AU - Rathore, Mobeen

AU - Stowers, Kristi

AU - Usitalo, Ann

AU - Turpin, Delmyra

AU - Smith, Renee

AU - Watson, Douglas

AU - Stubbs, Latoya

AU - Belanger, Rose

AU - Dieudonne, Arry

AU - Bettica, Linda

AU - Adubato, Susan

AU - Scott, Gwendolyn

AU - Florez, Claudia

AU - Willen, Elizabeth

AU - Frederick, Toinette

AU - Davtyan, Mariam

AU - Mejia, Maribel

AU - Rodriguez, Zoe

AU - Heyer, Ibet

AU - Trifilio, Nydia Scalley

PY - 2015

Y1 - 2015

N2 - Objectives: We evaluated the potential cardiac effects of in-utero exposures to antiretroviral drugs in HIV-exposed but uninfected (HEU) children. Design and methods: We compared echocardiographic parameters of left ventricular function (ejection fraction, fractional shortening, and stress-velocity index) and structure (left ventricular dimension, posterior wall/septal thickness, mass, thickness-todimension ratio, and wall stress) (expressed as Z-scores to account for age and body surface area) between HEU and HIV-unexposed cohorts from the Pediatric HIV/AIDS Cohort Study's Surveillance Monitoring for ART Toxicities study. Within the HEU group, we investigated the associations between the echocardiographic Z-scores and in-utero exposures to maternal antiretroviral drugs . Results: There were no significant differences in echocardiographic Z-scores between 417HEUand 98 HIV-unexposed children aged 2-7 years. Restricting the analysis toHEU children, first-trimester exposures to combination antiretroviral therapy (a regimen including at least three antiretroviral drugs) and to certain specific antiretroviral drugs were associated with significantly lower stress-velocity Z-scores (mean decreases of 0.22-0.40 SDs). Exposure to combination antiretroviral therapy was also associated with lower left ventricular dimension Z-scores (mean decrease of 0.44 SD). First-trimester exposure to combination antiretroviral therapy was associated with higher mean left ventricular posterior wall thickness and lower mean left ventricular wall stress Z-scores . Conclusion: There was no evidence of significant cardiac toxicity of perinatal combination antiretroviral therapy exposure in HEU children. Subclinical differences in left ventricular structure and function with specific in-utero antiretroviral exposures indicate the need for a longitudinal cardiac study in HEU children to assess long-term cardiac risk and cardiac monitoring recommendations .

AB - Objectives: We evaluated the potential cardiac effects of in-utero exposures to antiretroviral drugs in HIV-exposed but uninfected (HEU) children. Design and methods: We compared echocardiographic parameters of left ventricular function (ejection fraction, fractional shortening, and stress-velocity index) and structure (left ventricular dimension, posterior wall/septal thickness, mass, thickness-todimension ratio, and wall stress) (expressed as Z-scores to account for age and body surface area) between HEU and HIV-unexposed cohorts from the Pediatric HIV/AIDS Cohort Study's Surveillance Monitoring for ART Toxicities study. Within the HEU group, we investigated the associations between the echocardiographic Z-scores and in-utero exposures to maternal antiretroviral drugs . Results: There were no significant differences in echocardiographic Z-scores between 417HEUand 98 HIV-unexposed children aged 2-7 years. Restricting the analysis toHEU children, first-trimester exposures to combination antiretroviral therapy (a regimen including at least three antiretroviral drugs) and to certain specific antiretroviral drugs were associated with significantly lower stress-velocity Z-scores (mean decreases of 0.22-0.40 SDs). Exposure to combination antiretroviral therapy was also associated with lower left ventricular dimension Z-scores (mean decrease of 0.44 SD). First-trimester exposure to combination antiretroviral therapy was associated with higher mean left ventricular posterior wall thickness and lower mean left ventricular wall stress Z-scores . Conclusion: There was no evidence of significant cardiac toxicity of perinatal combination antiretroviral therapy exposure in HEU children. Subclinical differences in left ventricular structure and function with specific in-utero antiretroviral exposures indicate the need for a longitudinal cardiac study in HEU children to assess long-term cardiac risk and cardiac monitoring recommendations .

KW - Antiretroviral drugs

KW - Cardiac

KW - HIV

KW - Pediatrics

KW - Toxicity

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