Neurodevelopmental outcomes in HIV-infected and uninfected African children

Beaudrap, Pierre De; Bodeau-Livinec, Florence; Pasquier, Estelle; Germanaud, David; Ndiang, Suzie Tetang; Nlend, Anne Njom; Ndongo, Francis Atéba; Guemkam, Georgette; Penda, Calixte Ida; Warszawski, Josiane; Koecher, Diavolana; Faye, Albert; Tejiokem, Mathurin Cyrille

doi:10.1097/qad.0000000000002023

“…With respect to trajectory patterns, we observed that PHIV children with early ART demonstrated a higher rate of typical developmental functioning than PHIV children with standard ART (77% vs. 57%). As such, this study highlighted the importance of ART initiation within three months of age to mitigate deleterious effects of HIV on early neurodevelopmental outcomes, as previously reported in South African studies .…”

Section: Discussionsupporting

confidence: 73%

Low risk of neurodevelopmental impairment among perinatally acquired HIV‐infected preschool children who received early antiretroviral treatment in Thailand

Jantarabenjakul

¹

,

Chonchaiya

²

,

Puthanakit

³

et al. 2019

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Introduction Antiretroviral therapy ( ART ) is recommended in perinatally HIV‐infect ed ( PHIV ) infants immediately upon diagnosis. We aimed to compare neurodevelopmental outcomes between PHIV children who initiated ART within 12 months of life and perinatally HIV‐ exposed uninfected ( PHEU ) children and to assess neurodevelopmental outcomes by timing of ART . Methods This prospective cohort study included Thai children aged 12 to 56 months who were assessed with the Mullen Scales of Early Learning ( MSEL ) at enrolment and at 48 weeks. Global Developmental Impairment ( GDI ) was defined as Early Learning Composite ( ELC ) ≤ 70 on the MSEL ; typical developmental pattern was defined as ELC > 70 at both visits. Logistic regression was used to compare prevalence of any GDI . Predictors of changing ELC scores were analysed with generalized estimating equations linear regression model. Results From 2016 to 2017, 50 PHIV (twenty‐seven early ART within three months and twenty‐three standard ART within three to twelve months) and 100 PHEU children were enrolled. Median ( IQR ) age at first assessment was 28 (19 to 41) months. PHIV children had lower age‐relevant Z scores for weight, height and head circumference compared to the PHEU group ( p < 0.05). The prevalence of overall GDI was 18% (95% CI 11 to 27) and 32% (95% CI 20 to 47) in PHEU and PHIV children respectively ( p = 0.06). In subgroup analysis, 22% (95% CI 9 to 42) of early ART PHIV children and 44% (95% CI 23 to 66) of standard ART PHIV children had overall GDI . There was a higher rate of GDI in standard ART PHIV children ( p = 0.01), but not in the early ART group ( p = 0.62) when compared with PHEU children. The standard ART PHIV group demonstrated lower typical developmental pattern than both the early ART P...

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“…However, recent analyses indicate that the neurocognitive advantages attributed to initiation of ART during the immediate postnatal period are not sustained for many individuals in later childhood [5]. Similar findings have been reported in separate cohorts of older children with pHIV who initiated suppressive ART within weeks of birth [6][7], as well as subgroups of children who initiated ART after surviving the first year of life without significant immune compromise [8][9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 65%

“…After birth, environmental pressures, including living with a chronic medical disease, moderate brain development and expression of brainbehavior phenotypes [35][36][37][38]. Many children infected with HIV also face chronic stress associated with poverty (food security and malnutrition, limited education, family and social support disruption; [6][7][8][9][10][11][12][13]). Stigma related to HIV and psychological challenges created by HIV disclosure among sexually active adolescents and young adults contribute to the burden of early life adversities in this vulnerable population [39].…”

Section: Discussionmentioning

confidence: 99%

Predicting neurodevelopmental outcomes in children with perinatal HIV using a novel machine learning algorithm

Paul

¹

,

Cho

²

,

Mellins

³

et al. 2019

Preprint

3

0

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Background: A subset of children with perinatal HIV (pHIV) experience long-term neurocognitive symptoms despite treatment with antiretroviral therapy. However, predictors of neurocognitive outcomes remain elusive, particularly for children with pHIV residing in low-tomiddle income countries. The present study utilized a novel data analytic approach to identify clinically-relevant predictors of neurocognitive development in children with pHIV. Methods:Analyses were conducted on a large repository of longitudinal data from 285 children with pHIV in Thailand (n=170) and Cambodia (n=115). Participants were designated as neurocognitively resilient (i.e., positive slope; n=143) or at risk (i.e., negative slope; n=142) according to annual performances on the Beery-Buktenica Developmental Test of Visual-Motor Integration over an average of 5.4 years. Gradient-boosted multivariate regression (GBM) with 5-fold cross validation was utilized to identify the optimal combination of demographic, HIV disease, blood markers, and emotional health indices that predicted classification into the two neurocognitive subgroups. Model performance was assessed using Receiver Operator Curves and sensitivity/specificity. Results: The analytic approach distinguished neurocognitive subgroups with high accuracy (93%; sensitivity and specificity each > 90%). Dynamic change indices and interactions between mental health and biological indices emerged as key predictors. Conclusion: Machine learning-based regression defined a unique explanatory model of neurocognitive outcomes among children with pHIV. The predictive algorithm included a combination of HIV, physical health, and mental health indices extracted from readily available clinical measures. Studies are needed to explore the clinical relevance of the data-driven explanatory model, including potential to inform targeted interventions aimed at modifiable risk factors.

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“…A meta‐analysis on neurodevelopment in HIV‐exposed uninfected (HEU) children highlighted the limitations in the current body of literature including the heterogeneity of the patient populations between studies, limited confounders measured and variability in ART regimens. More recent studies are often limited by sample size and have mixed results .…”

Section: Introductionmentioning

confidence: 99%

In utero exposure to HIV and/or antiretroviral therapy: a systematic review of preclinical and clinical evidence of cognitive outcomes

McHenry

¹

,

Balogun

²

,

McDonald

³

et al. 2019

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Introducion With the increasing number of children exposed to HIV or antiretroviral therapy in utero, there are concerns that this population may have worse neurodevelopmental outcomes compared to those who are unexposed. The objective of this study was to systematically review the clinical and preclinical literature on the effects of in utero exposure to HIV and/or antiretroviral therapy ( ART ) on neurodevelopment. Methods We systematically searched OVID Medline, Psyc INFO and Embase, as well as the Cochrane Collaborative Database, Google Scholar and bibliographies of pertinent articles. Titles, abstracts, and full texts were assessed independently by two reviewers. Data from included studies were extracted. Results are summarized qualitatively. Results The search yielded 3027 unique titles. Of the 255 critically reviewed full‐text articles, 25 met inclusion criteria for the systematic review. Five articles studied human subjects and looked at brain structure and function. The remaining 20 articles were preclinical studies that mostly focused on behavioural assessments in animal models. The few clinical studies had mixed results. Some clinical studies found no difference in white matter while others noted higher fractional anisotropy and lower mean diffusivity in the brains of HIV ‐exposed uninfected children compared to HIV ‐unexposed uninfected children, correlating with abnormal neurobehavioral scores. Preclinical studies focused primarily on neurobehavioral changes resulting from monotherapy with either zidovudine or lamivudine. Various developmental and behavioural changes were noted in preclinical studies with ART exposure, including decreased grooming, decreased attention, memory deficits and fewer behaviours associated with appropriate social interaction. Conclusions While the existing literature suggests that there may be some neurobehavioral differences associated with HIV and ART exposure, limited data are available to substantially support these claims. More research is needed comparing neurobiological factors between HIV ‐exposed uninfected and HIV ‐unexposed uninfected children and using exposures consistent with current clinical care.

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Neurodevelopmental outcomes in HIV-infected and uninfected African children

Cited by 31 publications

References 36 publications

Low risk of neurodevelopmental impairment among perinatally acquired HIV‐infected preschool children who received early antiretroviral treatment in Thailand

Low risk of neurodevelopmental impairment among perinatally acquired HIV‐infected preschool children who received early antiretroviral treatment in Thailand

Predicting neurodevelopmental outcomes in children with perinatal HIV using a novel machine learning algorithm

In utero exposure to HIV and/or antiretroviral therapy: a systematic review of preclinical and clinical evidence of cognitive outcomes

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