Safety of In Utero and Neonatal Antiretroviral Exposure

Nozyce, Molly; Huo, Yanling; Williams, Paige L.; Kapetanovic, Suad; Hazra, Rohan; Nichols, Sharon L.; Smith, Renee; Seage, George R.; Sirois, Patricia A.

doi:10.1097/inf.0000000000000410

Cited by 32 publications

(14 citation statements)

References 35 publications

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“…Similar findings were found in the PHACS cohort when assessing the effects of ART exposure as well as differing ART class regimens [83]. A more recent study within PHACS also evaluated cognitive outcomes in older HEU children and did not find associations between any perinatal ART class regimens and cognitive and academic scores [84]. One study from Thailand reported small reductions in Wechsler Intelligence Scale testing comparing HEU to HUU children but acknowledged the uncertainty around the long-term clinical significance of these findings [108].…”

Section: Discussionsupporting

confidence: 63%

“…What dictates “substantial” is debatable, but many consider outcomes involving birth weight [66–75], congenital defects [76–81], early neurodevelopment [82–84] and growth [70,75,85–87] as significant, and none of these have demonstrated a clear association with in utero HIV/ARV exposure (Table 3). Even pre-term birth, which has been shown in several studies to be associated with ART [74,89–92,95] is still an early infant outcome and would occur and be managed well before adolescence, the time of disclosure.…”

Section: Discussionmentioning

confidence: 99%

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Disclosing in utero HIV/ARV exposure to the HIV‐exposed uninfected adolescent: is it necessary?

Jao

Hazra

Mellins

et al. 2016

Journal of the International AIDS Society

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IntroductionThe tremendous success of antiretroviral therapy has resulted in a diminishing population of perinatally HIV-infected children on the one hand and a mounting number of HIV-exposed uninfected (HEU) children on the other. As the oldest of these HEU children are reaching adolescence, questions have emerged surrounding the implications of HEU status disclosure to these adolescents. This article outlines the arguments for and against disclosure of a child's HEU status.DiscussionDisclosure of a child's HEU status, by definition, requires disclosure of maternal HIV status. It is necessary to weigh the benefits and harms which could occur with disclosure in each of the following domains: psychosocial impact, long-term physical health of the HEU individual and the public health impact. Does disclosure improve or worsen the psychological health of the HEU individual and extended family unit? Do present data on the long-term safety of in utero HIV/ARV exposure reveal potential health risks which merit disclosure to the HEU adolescent? What research and public health programmes or systems need to be in place to afford monitoring of HEU individuals and which, if any, of these require disclosure?ConclusionsAt present, it is not clear that there is sufficient evidence on whether long-term adverse effects are associated with in utero HIV/ARV exposures, making it difficult to mandate universal disclosure. However, as more countries adopt electronic medical record systems, the HEU status of an individual should be an important piece of the health record which follows the infant not only through childhood and adolescence but also adulthood. Clinicians and researchers should continue to approach the dialogue around mother–child disclosure with sensitivity and a cogent consideration of the evolving risks and benefits as new information becomes available while also working to maintain documentation of an individual's perinatal HIV/ARV exposures as a vital part of his/her medical records. As more long-term adult safety data on in utero HIV/ARV exposures become available these decisions may become clearer, but at this time, they remain complex and multi-faceted.

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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Disclosing in utero HIV/ARV exposure to the HIV‐exposed uninfected adolescent: is it necessary?

Jao

Hazra

Mellins

et al. 2016

Journal of the International AIDS Society

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“…6, 7, 9 -11, 17 -19 Atazanavir has been implicated in possible language domain deficits in a number of studies in North America. 7,12,31 Only a small number of women were taking atazanavir-containing regimens during pregnancy in our study; hence, we did not have sufficient power to assess for expressive language deficits among our atazanavir exposed children.…”

Section: Discussionmentioning

confidence: 99%

Neurodevelopment of HIV-Exposed and HIV-Unexposed Uninfected Children at 24 Months

Chaudhury¹,

Williams

Mayondi

et al. 2017

Pediatrics

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“…For participants between 5 and 13 years of age, assessments included the Wechsler Preschool and Primary Scale of Intelligence-III (WPPSI-III) (age 5), the Wechsler Abbreviated Scale of Intelligence (ages 7, 9, 11, and 13) for cognitive status, and the Wechsler Abbreviated Individual Achievement Test (ages 7, 9, 11, and 13) for academic performance ( 42 ). We found no association between in utero exposure to any ARV regimen or class and any cognitive or academic outcome.…”

Section: Neurocognitive and Language Functioningmentioning

confidence: 99%

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

et al. 2016

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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.

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Safety of In Utero and Neonatal Antiretroviral Exposure

Cited by 32 publications

References 35 publications

Disclosing in utero HIV/ARV exposure to the HIV‐exposed uninfected adolescent: is it necessary?

Disclosing in utero HIV/ARV exposure to the HIV‐exposed uninfected adolescent: is it necessary?

Neurodevelopment of HIV-Exposed and HIV-Unexposed Uninfected Children at 24 Months

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

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