Working Memory Profiles in HIV-Exposed, Uninfected and HIV-Infected Children: A Comparison with Neurotypical Controls

Milligan, Robyn; Cockcroft, Kate

doi:10.3389/fnhum.2017.00348

Cited by 16 publications

(19 citation statements)

References 117 publications

(201 reference statements)

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“…Consistent with the findings of a study conducted among HIV-infected children on treatment in India, neurocognitive impairment was observed despite being on ART treatment for more than 2 years with an undetectable viral load and normal CD4 + cell count (23). Similar findings were found in a South African study that reported HIV-infected children with a median age of 5 years did not show improvement in neurocognitive function after 6 months of ART (24). In addition, the finding from the present study is consistent with studies showing that children infected with HIV relative to uninfected groups evidence focal neurocognitive deficits on task that measures working memory (25); processing speed (26); visual motor integration, sustained attention (27); and motor speed coordination (28).…”

Section: Discussionsupporting

confidence: 88%

Clinico-Immunological Status and Neurocognitive Function of Perinatally Acquired HIV-Positive Children on cART: A Cross-Sectional Correlational Study in South Africa

Lentoor

2020

Front. Neurol.

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Despite the undisputed benefits of combination antiretroviral therapy (cART), perinatally acquired human immunodeficiency virus (PHIV) children on treatment often present with a spectrum of neurological deficits known as HIV-associated neurocognitive impairment. Even higher CD4 cell count does not seem to prevent the development of neurocognitive impairment in children with PHIV. While CD4 cell count has shown to have the greatest prognostic value, its association with neurocognitive abilities remains to be clarified. This study aimed at determining the correlation between plasma CD4 + lymphocyte and neurocognitive function in children with PHIV on cART. In total, 152 purposively recruited hospital-based sample of children with PHIV on cART, aged 3 years to 7 years 6 months (mean age, 63.13 months), underwent neurocognitive assessment using the Wechsler Preschool and Primary Scale of Intelligence, Third Edition. Immunological status of each child was based on the plasma CD4 + lymphocyte levels. The mean CD4 + lymphocyte cell count at the time of neurocognitive assessment was 1,259.85 cells/mm 3 (mean range, 139-2,717 cells/mm 3), with significant age difference on CD4 + lymphocyte count levels [F (2,149) = 13.58, p = 0.000]. CD4 + lymphocyte counts was significantly correlated with subdomains of neurocognitive function scores of task that measures working memory, processing speed, and perceptual reasoning. Global cognitive ability (Full Scale Intellectual Quotient) had no significant association with immunological status of the children. The findings support an association between immunological status of PHIV infection and executive function task. These neurocognitive faculties are critical for learning, school readiness and success in early childhood, and ultimately treatment adherence in adolescence. The need for early identification of neurodevelopment deficits in children, even when on cART, is crucial because early psychosocial and neurorehabilitative interventions can lead to better outcome for children with PHIV.

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Section: Discussionsupporting

confidence: 88%

Clinico-Immunological Status and Neurocognitive Function of Perinatally Acquired HIV-Positive Children on cART: A Cross-Sectional Correlational Study in South Africa

Lentoor

2020

Front. Neurol.

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“…Similarly, studies of school-aged HEU children demonstrate subtle deficits compared to control children, particularly in language-related cognitive performance ( Van Rie et al, 2008 ; Kerr et al, 2014 ; Milligan and Cockcroft, 2017 ). A recent longitudinal study reported that neurodevelopment of HEU children is initially similar to their HIV-unexposed peers, but neurocognitive performance starts to fall behind that of HIV-unexposed children during childhood ( Smith et al, 2017 ).…”

Section: Discussionmentioning

confidence: 98%

Perinatal HIV Infection or Exposure Is Associated With Low N-Acetylaspartate and Glutamate in Basal Ganglia at Age 9 but Not 7 Years

Robertson

Holmes

Cotton

et al. 2018

Front. Hum. Neurosci.

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Abnormalities of the basal ganglia are frequently seen in HIV-infected (HIV+) children despite antiretroviral treatment (ART) initiation during childhood. Assessment of metabolites associated with neuronal integrity or with glial proliferation can present a sensitive description of metabolic events underlying basal ganglia structural changes. We used magnetic resonance spectroscopy to examine differences in creatine, choline, N-acetylaspartate (NAA), glutamate, and myo-inositol between HIV+ children and HIV-unexposed controls, as well as between HIV-exposed uninfected (HEU) children and HIV-unexposed controls at age 7 and at age 9. No differences in metabolites relative to the HIV-unexposed control group were found at age 7. However, at 9 years, both HIV+ and HEU had lower NAA and glutamate than unexposed control children. HEU children also had lower creatine and choline than control children. At age 7, lower CD4/CD8 ratio at enrollment was associated with lower choline levels. At age 9 lower CD4/CD8 at enrollment was associated with lower myo-inositol. Low NAA and glutamate at age 9, but not 7, suggest that basal ganglia neurons may be particularly affected by perinatal HIV/ART and that neuronal damage may be ongoing despite early ART and viral suppression. Reduced basal ganglia metabolite levels in HEU children suggest an effect of HIV exposure on childhood brain development that merits further investigation using neuroimaging and neurocognitive testing.

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“…For instance, deficits in semantic fluency performance might indicate difficulties in planning, monitoring and decision making. Furthermore, because previous research indicates that working memory scores predict reading and math achievement [ 33 ] these children may under‐achieve educationally.…”

Section: Discussionmentioning

confidence: 99%

Cognitive outcomes at ages seven and nine years in South African children from the children with HIV early antiretroviral (CHER) trial: a longitudinal investigation

et al. 2021

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Introduction: Many children living with HIV (CLWH) display impaired cognition. Although early combination antiretroviral therapy (ART) produces improved cognitive outcomes, more long-term outcome data are needed. After concluding the Children with HIV Early antiRetroviral (CHER) trial in 2011, we investigated cognitive performance, at seven and nine years of age. Participants had been randomized to deferred ART (ART-Def; n = 22); immediate time-limited ART for 40 weeks (ART-40W; n = 30) and immediate time-limited ART for 96 weeks (ART-96W; n = 18). We also recruited HIV-exposed uninfected (CHEU; n = 28) and HIV-unexposed (CHU; n = 35) children. Methods: Data were collected between May 2012 and December 2017. Mixed-model repeated-measures ANOVAs assessed differences over time between CLWH (ART-40W, ART-96W and ART-Def) and CHIV-CHEU and CHU between ART-Early (ART-40W and ART-96W), ART-Def, CHEU and CHU; and between ART-40W, ART-96W, ART-Def, CHEU and CHU. Results: All comparisons found significant effects of Time for most outcome variables (better scores at nine than at seven years; ps < 0.05). The first ANOVAs found that for (a) motor dexterity, CLWH performed worse than CHIV-at seven years (p < 0.001) but improved to equivalence at nine years, (b) visual-spatial processing and problem solving, only CLWH (p < 0.04) showed significant performance improvement over time and (c) working memory and executive function, CLWH performed worse than CHIV-at both seven and nine years (p = 0.03 and 0.04). The second ANOVAs found that for (a) working memory, CHU performed better than ART-Early and CHEU (p < 0.01 and <0.04), and (b) motor dexterity, ART-Def performed worse than ART-Early, CHEU and CHU at seven years (p = 0.02, <0.001 and <0.001 respectively) but improved to equivalence at nine years (ps > 0.17). Similarly, for motor dexterity, ART-Def performed worse than ART-96W, CHEU and CHU at seven years (p < 0.04, <0.001 and <0.001) but improved to equivalence at nine years (ps > 0.20). Conclusions: Although neurocognitive developmental trajectories for treatment groups and controls were largely similar (i.e. performance improvements from 7 to 9), all ART-treated children, regardless of treatment arm, remain at risk for cognitive deficits over early school ages. Although the nature of these deficits may change as cognitive development proceeds, there are potential negative consequences for these children's future learning, reasoning and adaptive functioning.

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Working Memory Profiles in HIV-Exposed, Uninfected and HIV-Infected Children: A Comparison with Neurotypical Controls

Cited by 16 publications

References 117 publications

Clinico-Immunological Status and Neurocognitive Function of Perinatally Acquired HIV-Positive Children on cART: A Cross-Sectional Correlational Study in South Africa

Clinico-Immunological Status and Neurocognitive Function of Perinatally Acquired HIV-Positive Children on cART: A Cross-Sectional Correlational Study in South Africa

Perinatal HIV Infection or Exposure Is Associated With Low N-Acetylaspartate and Glutamate in Basal Ganglia at Age 9 but Not 7 Years

Cognitive outcomes at ages seven and nine years in South African children from the children with HIV early antiretroviral (CHER) trial: a longitudinal investigation

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