Developmental delay and behavioral disorders in 59 HIV-exposed uninfected infants

Reliquet, Véronique; Brunet-Cartier, Cécile; Launay, Élise; Raffi, François

doi:10.21037/tp.2016.04.03

Cited by 3 publications

(1 citation statement)

References 13 publications

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“…Antiretroviral drugs can accumulate in the amniotic fluid [45], possibly explaining some adverse outcomes on foetal [46][47][48] and infant development [49][50][51][52]. Dolutegravir is slowly being introduced into clinical practice in SSA.…”

Section: Introductionmentioning

confidence: 99%

The University of Zimbabwe College of Health Sciences (UZ-CHS) BIRTH COHORT study: rationale, design and methods

Duri

Gumbo²,

Munjoma

et al. 2020

BMC Infect Dis

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Background Commencing lifelong antiretroviral therapy (ART) immediately following HIV diagnosis (Option B+), has greatly improved maternal-infant health. Thus, large and increasing numbers of HIV-infected women are on ART during pregnancy, a situation concurrently increasing numbers of HIV-exposed-uninfected (HEU) infants. Compared to their HIV-unexposed-uninfected (HUU) counterparts, HEU infants show higher rates of adverse birth outcomes, mortality, infectious/non-communicable diseases including impaired growth and neurocognitive development. There is an urgent need to understand the impact of HIV and early life ART exposures, immune-metabolic dysregulation, comorbidities and environmental confounders on adverse paediatric outcomes. Methods Six hundred (600) HIV-infected and 600 HIV-uninfected pregnant women ≥20 weeks of gestation will be enrolled from four primary health centres in high density residential areas of Harare. Participants will be followed up as mother-infant-pairs at delivery, week(s) 1, 6, 10, 14, 24, 36, 48, 72 and 96 after birth. Clinical, socio-economic, nutritional and environmental data will be assessed for adverse birth outcomes, impaired growth, immune/neurodevelopment, vertical transmission of HIV, hepatitis-B/C viruses, cytomegalovirus and syphilis. Maternal urine, stool, plasma, cord blood, amniotic fluid, placenta and milk including infant plasma, dried blood spot and stool will be collected at enrolment and follow-up visits. The composite primary endpoint is stillbirth and infant mortality within the first two years of life in HEU versus HUU infants. Maternal mortality in HIV-infected versus -uninfected women is another primary outcome. Secondary endpoints include a range of maternal and infant outcomes. Sub-studies will address maternal stress and malnutrition, maternal-infant latent tuberculosis, Helicobacter pylori infections, immune-metabolomic dysregulation including gut, breast milk and amniotic fluid dysbiosis. Discussion The University of Zimbabwe-College of Health-Sciences-Birth-Cohort study will provide a comprehensive assessment of risk factors and biomarkers for HEU infants’ adverse outcomes. This will ultimately help developing strategies to mitigate effects of maternal HIV, early-life ART exposures and comorbidities on infants’ mortality and morbidity. Trial registration ClinicalTrial.gov Identifier: NCT04087239. Registered 12 September 2019.

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Section: Introductionmentioning

confidence: 99%

The University of Zimbabwe College of Health Sciences (UZ-CHS) BIRTH COHORT study: rationale, design and methods

Duri

Gumbo²,

Munjoma

et al. 2020

BMC Infect Dis

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Neurodevelopmental outcomes and in-utero antiretroviral exposure in HIV-exposed uninfected children

Piske

Budd

Qiu

et al. 2018

Aids

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The results suggest no adverse associations between antiretroviral drugs and neurodevelopmental disorders within antiretroviral-exposed HEU children in our cohort. Prevalence of neurodevelopmental disorders is higher in HEUs; however, maternal substance use plays a role, as could other environmental factors not captured. These findings highlight a need for holistic support for pregnant women as well as careful developmental monitoring of HEUs past infancy, and access to early interventions, particularly among those born preterm and those exposed to addictive substances.

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Differential effects of antiretroviral drug toxicity in male versus female children who are HIV-exposed but uninfected

Gilmore

Serghides

Bendayan

2020

Aids

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In recent years, widespread use of antiretroviral therapy (ART) during pregnancy has been increasingly effective in reducing risk of vertical transmission of HIV, with over 80% of pregnant women living with HIV now accessing ART, and a 41% reduction in new infections in children between 2010 and 2018. Despite these strides, the developmental toxicity of widely administered antiretroviral drugs (ARVs) remains poorly described and existing literature often fails to account for fetal and infant sex as a variable. Recent reports have identified associations between in-utero exposure to commonly used antiretroviral regimens and alteration in neurodevelopment, growth, and metabolism amongst children who are HIV-exposed but uninfected, with findings of sex differences in the prevalence and severity of ARV toxicity. These differences are potentially explained by variable exposure to ARV drugs in utero or exacerbation of existing sex-linked risk factors. Fetal ARV exposure is mediated by placental and fetal drug transporters and metabolic enzymes, which may contribute to the manifestation of sex differences. Existing evidence of sex differences in ARV toxicity in fetal development is concerning, and demands further research to guide optimal treatment options for maternal health and prevention of vertical HIV transmission.

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Developmental delay and behavioral disorders in 59 HIV-exposed uninfected infants

Cited by 3 publications

References 13 publications

The University of Zimbabwe College of Health Sciences (UZ-CHS) BIRTH COHORT study: rationale, design and methods

The University of Zimbabwe College of Health Sciences (UZ-CHS) BIRTH COHORT study: rationale, design and methods

Neurodevelopmental outcomes and in-utero antiretroviral exposure in HIV-exposed uninfected children

Differential effects of antiretroviral drug toxicity in male versus female children who are HIV-exposed but uninfected

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