The PHACS SMARTT Study: Assessment of the Safety of In Utero Exposure to Antiretroviral Drugs
- PMID: 27242802
- PMCID: PMC4876360
- DOI: 10.3389/fimmu.2016.00199
The PHACS SMARTT Study: Assessment of the Safety of In Utero Exposure to Antiretroviral Drugs
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.
Figures
![Figure 1](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/4876360/bin/fimmu-07-00199-g001.gif)
![Figure 2](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/4876360/bin/fimmu-07-00199-g002.gif)
Similar articles
-
In Utero Antiretroviral Exposure and Risk of Neurodevelopmental Problems in HIV-Exposed Uninfected 5-Year-Old Children.AIDS Patient Care STDS. 2023 Mar;37(3):119-130. doi: 10.1089/apc.2022.0189. Epub 2023 Feb 24. AIDS Patient Care STDS. 2023. PMID: 36827595 Free PMC article.
-
Association of maternal antiretroviral use with microcephaly in children who are HIV-exposed but uninfected (SMARTT): a prospective cohort study.Lancet HIV. 2020 Jan;7(1):e49-e58. doi: 10.1016/S2352-3018(19)30340-6. Epub 2019 Nov 15. Lancet HIV. 2020. PMID: 31740351 Free PMC article.
-
Congenital anomalies and in utero antiretroviral exposure in human immunodeficiency virus-exposed uninfected infants.JAMA Pediatr. 2015 Jan;169(1):48-55. doi: 10.1001/jamapediatrics.2014.1889. JAMA Pediatr. 2015. PMID: 25383770 Free PMC article.
-
HIV exposure through contact with body fluids.Prescrire Int. 2012 Apr;21(126):100-1, 103-5. Prescrire Int. 2012. PMID: 22515138 Review.
-
A survey of the syntheses of active pharmaceutical ingredients for antiretroviral drug combinations critical to access in emerging nations.Antiviral Res. 2008 Sep;79(3):143-65. doi: 10.1016/j.antiviral.2008.05.001. Epub 2008 Jun 2. Antiviral Res. 2008. PMID: 18571246 Review.
Cited by
-
Neurodevelopment among children exposed to HIV and uninfected in sub-Saharan Africa.J Int AIDS Soc. 2023 Oct;26 Suppl 4(Suppl 4):e26159. doi: 10.1002/jia2.26159. J Int AIDS Soc. 2023. PMID: 37909232 Free PMC article.
-
Strengthening the evidence to improve health outcomes of children with perinatal HIV exposure.J Int AIDS Soc. 2023 Oct;26 Suppl 4(Suppl 4):e26160. doi: 10.1002/jia2.26160. J Int AIDS Soc. 2023. PMID: 37909219 Free PMC article.
-
Factors associated with internalized HIV-related stigma among biological mothers living with HIV enrolled in a US cohort study.AIDS Care. 2024 Feb;36(2):220-226. doi: 10.1080/09540121.2023.2263680. Epub 2024 Jan 30. AIDS Care. 2024. PMID: 37757482
-
Enhancing interventions for prevention of mother-to-child- transmission of hepatitis B virus.JHEP Rep. 2023 Apr 24;5(8):100777. doi: 10.1016/j.jhepr.2023.100777. eCollection 2023 Aug. JHEP Rep. 2023. PMID: 37554925 Free PMC article. Review.
-
In Utero Antiretroviral Exposure and Risk of Neurodevelopmental Problems in HIV-Exposed Uninfected 5-Year-Old Children.AIDS Patient Care STDS. 2023 Mar;37(3):119-130. doi: 10.1089/apc.2022.0189. Epub 2023 Feb 24. AIDS Patient Care STDS. 2023. PMID: 36827595 Free PMC article.
References
-
- CDC. Enhanced Perinatal Surveillance – 15 Areas, 2005-2008. (2016). Available from: http://www.cdc.gov/hiv/pdf/statistics_2005_2008_HIV_Surveillance_Report_...
-
- The Perinatal Safety Review Working Group. Nucleoside exposure in the children of HIV-infected women receiving antiretroviral drugs: absence of clear evidence for mitochondrial disease in children who died before 5 years of age in five United States cohorts. J Acquir Immune Defic Syndr (2000) 25(3):261–8. - PubMed
Publication types
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous