First-trimester exposure to newer antiretroviral agents and congenital anomalies in a US cohort

Kelly Fung; Sonia Hernandez-Diaz; Rebecca Zash; Ellen G. Chadwick; Russell B. Van Dyke; Carly Broadwell; Jennifer Jao; Kathleen Powis; Lynn M. Yee; Paige L. Williams

doi:10.1097/QAD.0000000000003955

First-trimester exposure to newer antiretroviral agents and congenital anomalies in a US cohort

Kelly Fung, Sonia Hernandez-Diaz, Rebecca Zash, Ellen G. Chadwick, Russell B. Van Dyke, Carly Broadwell, Jennifer Jao, Kathleen Powis, Lynn M. Yee, Paige L. Williams^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

Objective:To characterize associations of exposure to newer antiretroviral medications in the first trimester with congenital anomalies among infants born to persons with HIV in the United States.Design:Longitudinal cohort of infants born 2012-2022 to pregnant persons with HIV enrolled in the Surveillance Monitoring for ART Toxicities (SMARTT) study.Methods:First-trimester exposures to newer antiretrovirals (ARVs) were abstracted from maternal medical records. Trained site staff conducted physical exams and abstracted congenital anomalies from infant medical records. Investigators classified anomalies using the Metropolitan Atlanta Congenital Defects Program classification system. The prevalence of major congenital anomalies identified by age one year was estimated for infants exposed and unexposed to each ARV. Generalized estimating equation models were used to estimate the odds ratio (OR) of major congenital anomalies for each ARV exposure, adjusting for potential confounders.Results:Of 2034 infants, major congenital anomalies were identified in 135 [6.6%; 95% confidence interval (CI): 5.6-7.8%]. Cardiovascular (n = 43) and musculoskeletal (n = 37) anomalies were the most common. Adjusted ORs (95% CI) of congenital anomalies were 1.03 (0.62-1.72) for darunavir, 0.91 (0.46-1.81) for raltegravir, 1.04 (0.58-1.85) for rilpivirine, 1.31 (0.71-2.41) for elvitegravir, 0.76 (0.37-1.57) for dolutegravir, and 0.34 (0.05-2.51) for bictegravir, compared to those unexposed to each specific ARV. Findings were similar after adjustment for nucleoside/nucleotide backbones.Conclusions:The odds of congenital anomalies among infants with first-trimester exposure to newer ARVs did not differ substantially from those unexposed to these specific ARVs, which is reassuring. Continued evaluation of these ARVs with larger studies will be needed to confirm these findings.

Original language	English (US)
Pages (from-to)	1686-1695
Number of pages	10
Journal	AIDS
Volume	38
Issue number	11
DOIs	https://doi.org/10.1097/QAD.0000000000003955
State	Published - Sep 1 2024

Funding

We thank the participants and families for their participation in PHACS, and the individuals and institutions involved in the conduct of PHACS. The Pediatric HIV/AIDS Cohort Study (PHACS) network was supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD), Office of The Director, National Institutes of Health (OD), National Institute of Dental & Craniofacial Research (NIDCR), National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Neurological Disorders and Stroke (NINDS), National Institute on Deafness and Other Communication Disorders (NIDCD), National Institute of Mental Health (NIMH), National Institute on Drug Abuse (NIDA), National Cancer Institute (NCI), National Institute on Alcohol Abuse and Alcoholism (NIAAA), and the National Heart, Lung, and Blood Institute (NHLBI) through grants to the Harvard T.H. Chan School of Public Health (P01HD103133, Principal Investigators: Ellen Chadwick, Sonia Hernandez-Diaz, Jennifer Jao, Paige Williams; Program Director: Liz Salomon and HD052102: Principal Investigator: George R Seage III; Program Director: Liz Salomon) and with 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 (Data Management Center Director: Suzanne Siminski), and regulatory services and logistical support were provided by Westat, Inc (Project Director: Tracy Wolbach). Sources of funding: The Pediatric HIV/AIDS Cohort Study (PHACS) network was supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD), Office of The Director, National Institutes of Health (OD), National Institute of Dental & Craniofacial Research (NIDCR), National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Neurological Disorders and Stroke (NINDS), National Institute on Deafness and Other Communication Disorders (NIDCD), National Institute of Mental Health (NIMH), National Institute on Drug Abuse (NIDA), National Cancer Institute (NCI), National Institute on Alcohol Abuse and Alcoholism (NIAAA), and the National Heart, Lung, and Blood Institute (NHLBI) through grants to the Harvard T.H. Chan School of Public Health (P01HD103133 and HD052102) and with Tulane University School of Medicine (HD052104).

Keywords

HIV
antiretroviral agents
congenital anomalies
pregnancy
teratogenicity

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1097/QAD.0000000000003955

Cite this

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title = "First-trimester exposure to newer antiretroviral agents and congenital anomalies in a US cohort",

abstract = "Objective:To characterize associations of exposure to newer antiretroviral medications in the first trimester with congenital anomalies among infants born to persons with HIV in the United States.Design:Longitudinal cohort of infants born 2012-2022 to pregnant persons with HIV enrolled in the Surveillance Monitoring for ART Toxicities (SMARTT) study.Methods:First-trimester exposures to newer antiretrovirals (ARVs) were abstracted from maternal medical records. Trained site staff conducted physical exams and abstracted congenital anomalies from infant medical records. Investigators classified anomalies using the Metropolitan Atlanta Congenital Defects Program classification system. The prevalence of major congenital anomalies identified by age one year was estimated for infants exposed and unexposed to each ARV. Generalized estimating equation models were used to estimate the odds ratio (OR) of major congenital anomalies for each ARV exposure, adjusting for potential confounders.Results:Of 2034 infants, major congenital anomalies were identified in 135 [6.6%; 95% confidence interval (CI): 5.6-7.8%]. Cardiovascular (n = 43) and musculoskeletal (n = 37) anomalies were the most common. Adjusted ORs (95% CI) of congenital anomalies were 1.03 (0.62-1.72) for darunavir, 0.91 (0.46-1.81) for raltegravir, 1.04 (0.58-1.85) for rilpivirine, 1.31 (0.71-2.41) for elvitegravir, 0.76 (0.37-1.57) for dolutegravir, and 0.34 (0.05-2.51) for bictegravir, compared to those unexposed to each specific ARV. Findings were similar after adjustment for nucleoside/nucleotide backbones.Conclusions:The odds of congenital anomalies among infants with first-trimester exposure to newer ARVs did not differ substantially from those unexposed to these specific ARVs, which is reassuring. Continued evaluation of these ARVs with larger studies will be needed to confirm these findings.",

keywords = "HIV, antiretroviral agents, congenital anomalies, pregnancy, teratogenicity",

author = "Kelly Fung and Sonia Hernandez-Diaz and Rebecca Zash and Chadwick, {Ellen G.} and {Van Dyke}, {Russell B.} and Carly Broadwell and Jennifer Jao and Kathleen Powis and Yee, {Lynn M.} and Williams, {Paige L.}",

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doi = "10.1097/QAD.0000000000003955",

language = "English (US)",

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pages = "1686--1695",

journal = "AIDS",

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T1 - First-trimester exposure to newer antiretroviral agents and congenital anomalies in a US cohort

AU - Fung, Kelly

AU - Hernandez-Diaz, Sonia

AU - Zash, Rebecca

AU - Chadwick, Ellen G.

AU - Van Dyke, Russell B.

AU - Broadwell, Carly

AU - Jao, Jennifer

AU - Powis, Kathleen

AU - Yee, Lynn M.

AU - Williams, Paige L.

PY - 2024/9/1

Y1 - 2024/9/1

N2 - Objective:To characterize associations of exposure to newer antiretroviral medications in the first trimester with congenital anomalies among infants born to persons with HIV in the United States.Design:Longitudinal cohort of infants born 2012-2022 to pregnant persons with HIV enrolled in the Surveillance Monitoring for ART Toxicities (SMARTT) study.Methods:First-trimester exposures to newer antiretrovirals (ARVs) were abstracted from maternal medical records. Trained site staff conducted physical exams and abstracted congenital anomalies from infant medical records. Investigators classified anomalies using the Metropolitan Atlanta Congenital Defects Program classification system. The prevalence of major congenital anomalies identified by age one year was estimated for infants exposed and unexposed to each ARV. Generalized estimating equation models were used to estimate the odds ratio (OR) of major congenital anomalies for each ARV exposure, adjusting for potential confounders.Results:Of 2034 infants, major congenital anomalies were identified in 135 [6.6%; 95% confidence interval (CI): 5.6-7.8%]. Cardiovascular (n = 43) and musculoskeletal (n = 37) anomalies were the most common. Adjusted ORs (95% CI) of congenital anomalies were 1.03 (0.62-1.72) for darunavir, 0.91 (0.46-1.81) for raltegravir, 1.04 (0.58-1.85) for rilpivirine, 1.31 (0.71-2.41) for elvitegravir, 0.76 (0.37-1.57) for dolutegravir, and 0.34 (0.05-2.51) for bictegravir, compared to those unexposed to each specific ARV. Findings were similar after adjustment for nucleoside/nucleotide backbones.Conclusions:The odds of congenital anomalies among infants with first-trimester exposure to newer ARVs did not differ substantially from those unexposed to these specific ARVs, which is reassuring. Continued evaluation of these ARVs with larger studies will be needed to confirm these findings.

AB - Objective:To characterize associations of exposure to newer antiretroviral medications in the first trimester with congenital anomalies among infants born to persons with HIV in the United States.Design:Longitudinal cohort of infants born 2012-2022 to pregnant persons with HIV enrolled in the Surveillance Monitoring for ART Toxicities (SMARTT) study.Methods:First-trimester exposures to newer antiretrovirals (ARVs) were abstracted from maternal medical records. Trained site staff conducted physical exams and abstracted congenital anomalies from infant medical records. Investigators classified anomalies using the Metropolitan Atlanta Congenital Defects Program classification system. The prevalence of major congenital anomalies identified by age one year was estimated for infants exposed and unexposed to each ARV. Generalized estimating equation models were used to estimate the odds ratio (OR) of major congenital anomalies for each ARV exposure, adjusting for potential confounders.Results:Of 2034 infants, major congenital anomalies were identified in 135 [6.6%; 95% confidence interval (CI): 5.6-7.8%]. Cardiovascular (n = 43) and musculoskeletal (n = 37) anomalies were the most common. Adjusted ORs (95% CI) of congenital anomalies were 1.03 (0.62-1.72) for darunavir, 0.91 (0.46-1.81) for raltegravir, 1.04 (0.58-1.85) for rilpivirine, 1.31 (0.71-2.41) for elvitegravir, 0.76 (0.37-1.57) for dolutegravir, and 0.34 (0.05-2.51) for bictegravir, compared to those unexposed to each specific ARV. Findings were similar after adjustment for nucleoside/nucleotide backbones.Conclusions:The odds of congenital anomalies among infants with first-trimester exposure to newer ARVs did not differ substantially from those unexposed to these specific ARVs, which is reassuring. Continued evaluation of these ARVs with larger studies will be needed to confirm these findings.

KW - HIV

KW - antiretroviral agents

KW - congenital anomalies

KW - pregnancy

KW - teratogenicity

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First-trimester exposure to newer antiretroviral agents and congenital anomalies in a US cohort

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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