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Van Dyke RB, Chadwick EG, Hazra R, et al. The PHACS SMARTT Study: Assessment of the Safety of In Utero Exposure to Antiretroviral Drugs. Front Immunol. 2016;7:199doi: 10.3389/fimmu.2016.00199.
Van Dyke, R. B., Chadwick, E. G., Hazra, R., Williams, P. L., & Seage, G. R. (2016). The PHACS SMARTT Study: Assessment of the Safety of In Utero Exposure to Antiretroviral Drugs. Frontiers in immunology, 7199. https://doi.org/10.3389/fimmu.2016.00199
Van Dyke, Russell B, et al. "The PHACS SMARTT Study: Assessment of the Safety of In Utero Exposure to Antiretroviral Drugs." Frontiers in immunology vol. 7 (2016): 199. doi: https://doi.org/10.3389/fimmu.2016.00199
Van Dyke RB, Chadwick EG, Hazra R, Williams PL, Seage GR. The PHACS SMARTT Study: Assessment of the Safety of In Utero Exposure to Antiretroviral Drugs. Front Immunol. 2016 May 23;7:199. doi: 10.3389/fimmu.2016.00199. eCollection 2016. PMID: 27242802; PMCID: PMC4876360.
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Front Immunol. 2016 May 23;7:199. doi: 10.3389/fimmu.2016.00199. eCollection 2016.

The PHACS SMARTT Study: Assessment of the Safety of In Utero Exposure to Antiretroviral Drugs.

Frontiers in immunology

Russell B Van Dyke, Ellen Gould Chadwick, Rohan Hazra, Paige L Williams, George R Seage

Affiliations

  1. Department of Pediatrics, Tulane University School of Medicine , New Orleans, LA , USA.
  2. Department of Pediatrics, Feinberg School of Medicine, Northwestern University (NUFSM) , Chicago, IL , USA.
  3. Eunice Kennedy Shriver National Institute of Child Health and Human Development , Bethesda, MD , USA.
  4. Department of Biostatistics, Harvard T.H. Chan School of Public Health , Boston, MA , USA.
  5. Department of Epidemiology, Harvard T.H. Chan School of Public Health , Boston, MA , USA.

PMID: 27242802 PMCID: PMC4876360 DOI: 10.3389/fimmu.2016.00199

Abstract

The Surveillance Monitoring for ART Toxicities (SMARTT) cohort of the Pediatric HIV/AIDS Cohort Study includes over 3,500 HIV-exposed but uninfected infants and children at 22 sites in the US, including Puerto Rico. The goal of the study is to determine the safety of in utero exposure to antiretrovirals (ARVs) and to estimate the incidence of adverse events. Domains being assessed include metabolic, growth and development, cardiac, neurological, neurodevelopmental (ND), behavior, language, and hearing. SMARTT employs an innovative trigger-based design as an efficient means to identify and evaluate adverse events. Participants who met a predefined clinical or laboratory threshold (trigger) undergo additional evaluations to define their case status. After adjusting for birth cohort and other factors, there was no significant increase in the likelihood of meeting overall case status (case in any domain) with exposure to combination ARVs (cARVs), any ARV class, or any specific ARV. However, several individual ARVs were significantly associated with case status in individual domains, including zidovudine for a metabolic case, first trimester stavudine for a language case, and didanosine plus stavudine for a ND case. We found an increased rate of preterm birth with first trimester exposure to protease inhibitor-based cARV. Although there was no overall increase in congenital anomalies with first trimester cARV, a significant increase was seen with exposure to atazanavir, ritonavir, and didanosine plus stavudine. Tenofovir exposure was associated with significantly lower mean whole-body bone mineral content in the newborn period and a lower length and head circumference at 1 year of age. With ND testing at 1 year of age, specific ARVs (atazanavir, ritonavir-boosted lopinavir, nelfinavir, and tenofovir) were associated with lower performance, although all groups were within the normal range. No ARVs or classes were associated with lower performance between 5 and 13 years of age. Atazanavir and saquinavir exposure were associated with late language emergence at 1 year, but not at 2 years of age. The results of the SMARTT study are generally reassuring, with little evidence for serious adverse events resulting from in utero ARV exposure. However, several findings of concern warrant further evaluation, and new ARVs used in pregnancy need to be evaluated.

Keywords: HIV exposure; antiretroviral drugs; children; in utero; infant; newborn; safety; toxicity

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