TY - JOUR
T1 - Long-Term Effects of in Utero Antiretroviral Exposure
T2 - Systolic and Diastolic Function in HIV-Exposed Uninfected Youth
AU - Guerra, Vitor
AU - Leister, Erin C.
AU - Williams, Paige L.
AU - Starc, Thomas J.
AU - Lipshultz, Steven E.
AU - Wilkinson, James D.
AU - Van Dyke, Russell B.
AU - Hazra, Rohan
AU - Colan, Steven D.
N1 - Funding Information:
The authors thank the children and families for their participation in PHACS and the individuals and institutions involved in the conduct of PHACS. The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development with cofunding from the National Institute on Drug Abuse, the National Institute of Allergy and Infectious Diseases, the Office of AIDS Research, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, the National Institute on Deafness and Other Communication Disorders, the National Heart, Lung, and Blood Institute, the National Institute of Dental and Craniofacial Research, and the National Institute on Alcohol Abuse and Alcoholism, through cooperative agreements with the Harvard T. H. Chan School of Public Health (HD052102, 3 U01 HD052102-05S1, 3 U01HD052102-06S3) and the Tulane University School of Medicine (HD052104, 3U01HD052104-06S1). Data management services were provided by Frontier Science and Technology Research Foundation, and regulatory services and logistical support were provided by Westat, Inc. The Pediatric HIV/AIDS Cohort Study (PHACS) was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development with cofunding from the National Institute on Drug Abuse, the National Institute of Allergy and Infectious Diseases, the Office of AIDS Research, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, the National Institute on Deafness and Other Communication Disorders, the National Heart, Lung, and Blood Institute, the National Institute of Dental and Craniofacial Research, and the National Institute on Alcohol Abuse and Alcoholism, through cooperative agreements with the Harvard T. H. Chan School of Public Health (HD052102, 3 U01 HD052102-05S1, 3 U01HD052102-06S3) and the Tulane University School of Medicine (HD052104, 3U01HD052104-06S1). NIH representatives were part of the study team and therefore the sponsor was involved in study design, coordination, data collection, data analysis, data interpretation, and writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication
Publisher Copyright:
© Copyright 2016, Mary Ann Liebert, Inc. 2016.
PY - 2016/7/1
Y1 - 2016/7/1
N2 - The aim of this study was to evaluate the association of in utero exposure to highly active antiretroviral therapy (HAART) with left ventricular (LV) function and structure in HIV-exposed uninfected (HEU) children. A prospective, multisite cohort study in HEU children was conducted by the Pediatric HIV/AIDS Cohort Study (PHACS). Echocardiographic measures of LV systolic and diastolic function and cardiac structure were obtained from HEU subjects aged ≥6 years enrolled in the PHACS Surveillance Monitoring of ART Toxicities study. Echocardiographic Z-scores were calculated using normative data from an established reference cohort. We used adjusted linear regression models to compare Z-scores for echocardiographic measures from HEU children exposed in utero to HAART with those exposed to non-HAART, adjusting for demographic and maternal health characteristics. One hundred seventy-four HEU subjects with echocardiograms and maternal ARV information were included (mean age 10.9 years; 48% male, 56% black non-Hispanic). Among 156 HEU youth with any ARV exposure, we observed no differences in Z-scores for LV systolic function measures between youth exposed in utero to HAART (39%) and HAART-unexposed youth in either unadjusted or adjusted models. In adjusted models, those exposed to HAART had significantly lower mitral late diastolic inflow velocities (adjusted mean Z-score = 0.00 vs. 0.52, p = .04) and significantly higher adjusted mean LV mass-to-volume ratio Z-scores (adjusted mean Z-score = 0.47 vs. 0.11, p = .03) than HAART-unexposed youth. Uninfected children with perinatal exposure to HAART had no difference in LV systolic function. However, small but significant differences in LV diastolic function and cardiac structure were observed, suggesting that continued monitoring for cardiac outcomes is warranted in this population.
AB - The aim of this study was to evaluate the association of in utero exposure to highly active antiretroviral therapy (HAART) with left ventricular (LV) function and structure in HIV-exposed uninfected (HEU) children. A prospective, multisite cohort study in HEU children was conducted by the Pediatric HIV/AIDS Cohort Study (PHACS). Echocardiographic measures of LV systolic and diastolic function and cardiac structure were obtained from HEU subjects aged ≥6 years enrolled in the PHACS Surveillance Monitoring of ART Toxicities study. Echocardiographic Z-scores were calculated using normative data from an established reference cohort. We used adjusted linear regression models to compare Z-scores for echocardiographic measures from HEU children exposed in utero to HAART with those exposed to non-HAART, adjusting for demographic and maternal health characteristics. One hundred seventy-four HEU subjects with echocardiograms and maternal ARV information were included (mean age 10.9 years; 48% male, 56% black non-Hispanic). Among 156 HEU youth with any ARV exposure, we observed no differences in Z-scores for LV systolic function measures between youth exposed in utero to HAART (39%) and HAART-unexposed youth in either unadjusted or adjusted models. In adjusted models, those exposed to HAART had significantly lower mitral late diastolic inflow velocities (adjusted mean Z-score = 0.00 vs. 0.52, p = .04) and significantly higher adjusted mean LV mass-to-volume ratio Z-scores (adjusted mean Z-score = 0.47 vs. 0.11, p = .03) than HAART-unexposed youth. Uninfected children with perinatal exposure to HAART had no difference in LV systolic function. However, small but significant differences in LV diastolic function and cardiac structure were observed, suggesting that continued monitoring for cardiac outcomes is warranted in this population.
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U2 - 10.1089/aid.2015.0281
DO - 10.1089/aid.2015.0281
M3 - Review article
C2 - 26794032
AN - SCOPUS:84976510184
VL - 32
SP - 621
EP - 627
JO - AIDS Research and Human Retroviruses
JF - AIDS Research and Human Retroviruses
SN - 0889-2229
IS - 7
ER -