TY - JOUR
T1 - Safety of in-utero antiretroviral exposure
T2 - Neurologic outcomes in children who are HIV-exposed but uninfected
AU - Crowell, Claudia S.
AU - Williams, Paige L.
AU - Yildirim, Cenk
AU - Van Dyke, Russell B.
AU - Smith, Renee
AU - Chadwick, Ellen G.
AU - Seage, George R.
AU - Diperna, Alexandria
AU - Hazra, Rohan
N1 - Funding Information:
Funding: The Pediatric HIV/AIDS Cohort Study (PHACS) was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) with co-funding from the National Institute of Dental and Craniofacial Research (NIDCR), the National Institute of Allergy and Infectious Diseases (NIAID), the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute on Deafness and Other Communication Disorders (NIDCD), Office of AIDS Research (OAR), the National Institute of Mental Health (NIMH), the National Institute on Drug Abuse (NIDA), and the National Institute on Alcohol Abuse and Alcoholism (NIAAA), through Cooperative agreements with the Harvard T.H. Chan School of Public Health (HD052102) and the Tulane University School of Medicine (HD052104).
Funding Information:
We 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 co-funding 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 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) (Principal Investigator: George Seage; Program Director: Julie Alperen) and the Tulane University School of Medicine (HD052104) (Principal Investigator: Russell Van Dyke; Co-Principal Investigator: Ellen Chadwick; Project Director: Patrick Davis). Data management services were provided by Frontier Science and Technology Research Foundation (PI: Suzanne Siminski), and regulatory services and logistical support were provided by Westat, Inc (PI: Julie Davidson).
Publisher Copyright:
© 2020 Lippincott Williams and Wilkins. All rights reserved.
PY - 2020/7/15
Y1 - 2020/7/15
N2 - Objective:To evaluate whether there is an increased risk of neurologic diagnoses in children who are HIV-exposed but uninfected (CHEU) exposed in utero to specific antiretroviral medications.Design:Prospective cohort study of CHEU enrolled from 2007 to 2017.Methods:We evaluated children for neurologic case status, including microcephaly, febrile seizures, seizure disorders, ophthalmologic disorders, and other neurologic disorders. Adjusted relative risks (aRRs) were estimated for the association between in-utero antiretroviral exposure and neurologic case using log-binomial regression, accounting for potential confounders. Sensitivity analyses were conducted to evaluate robustness of findings.Results:Among 3747 eligible CHEU, 231 (6.2%) met neurologic case criteria (95% CI 5.4 - 7%). Most eligible children (86%) were exposed in utero to combination antiretroviral regimens. In adjusted models, children exposed to efavirenz at any time during pregnancy had higher risk of neurologic case status (aRR = 1.53, 95% CI 0.94 - 2.51). This association was stronger when comparing efavirenz exposure at conception to no exposure during pregnancy (aRR = 1.92, 95% CI 1.09 - 3.36) and considering follow-up and case diagnosis only through age 2 (aRR = 2.14, 95% CI 1.11 - 4.12). Children exposed to didanosine at conception and during the first trimester had increased risk of neurologic case status (aRR = 2.28, 95% CI 1.07 - 4.87 and aRR = 2.02, 95% CI 1.01 - 4.04, respectively), compared with didanosine-unexposed children. Children with dolutegravir exposure had some suggestion of increased risk of neurologic case (aRR = 2.43, 95% CI 0.75 - 7.84), which was observed consistently across several sensitivity analyses.Conclusion:Efavirenz and didanosine exposure during pregnancy were associated with higher risk of neurologic abnormalities in CHEU, and dolutegravir exposure showed some suggestive associations, which warrant further monitoring.
AB - Objective:To evaluate whether there is an increased risk of neurologic diagnoses in children who are HIV-exposed but uninfected (CHEU) exposed in utero to specific antiretroviral medications.Design:Prospective cohort study of CHEU enrolled from 2007 to 2017.Methods:We evaluated children for neurologic case status, including microcephaly, febrile seizures, seizure disorders, ophthalmologic disorders, and other neurologic disorders. Adjusted relative risks (aRRs) were estimated for the association between in-utero antiretroviral exposure and neurologic case using log-binomial regression, accounting for potential confounders. Sensitivity analyses were conducted to evaluate robustness of findings.Results:Among 3747 eligible CHEU, 231 (6.2%) met neurologic case criteria (95% CI 5.4 - 7%). Most eligible children (86%) were exposed in utero to combination antiretroviral regimens. In adjusted models, children exposed to efavirenz at any time during pregnancy had higher risk of neurologic case status (aRR = 1.53, 95% CI 0.94 - 2.51). This association was stronger when comparing efavirenz exposure at conception to no exposure during pregnancy (aRR = 1.92, 95% CI 1.09 - 3.36) and considering follow-up and case diagnosis only through age 2 (aRR = 2.14, 95% CI 1.11 - 4.12). Children exposed to didanosine at conception and during the first trimester had increased risk of neurologic case status (aRR = 2.28, 95% CI 1.07 - 4.87 and aRR = 2.02, 95% CI 1.01 - 4.04, respectively), compared with didanosine-unexposed children. Children with dolutegravir exposure had some suggestion of increased risk of neurologic case (aRR = 2.43, 95% CI 0.75 - 7.84), which was observed consistently across several sensitivity analyses.Conclusion:Efavirenz and didanosine exposure during pregnancy were associated with higher risk of neurologic abnormalities in CHEU, and dolutegravir exposure showed some suggestive associations, which warrant further monitoring.
KW - HIV
KW - antiretroviral agents
KW - long-term adverse effects
KW - neurologic manifestations
KW - pediatrics
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U2 - 10.1097/QAD.0000000000002550
DO - 10.1097/QAD.0000000000002550
M3 - Article
C2 - 32310900
AN - SCOPUS:85087320381
SN - 0269-9370
VL - 34
SP - 1377
EP - 1387
JO - AIDS
JF - AIDS
IS - 9
ER -
