A detailed analysis of 35 studies suggests that perinatal transmission of HIV to newborns may be associated with serious cognitive deficits as children grow older, according to neuroscientists.
The finding helps pinpoint the geographic regions and factors that may be important for brain development outcomes related to perinatal HIV infection: mother-to-child HIV transmission during pregnancy, labour and delivery, or breastfeeding, they said.
Their research appeared in The Lancet’s eClinicalMedicine.
Mostly because of advances in antiretroviral therapies, Aids has largely become a chronic disease rather than a life-threatening condition. Worldwide, there are nearly 3m children and adolescents with HIV and more than 300 000 new HIV infections occurring annually.
“Despite achieving a perinatal HIV transmission rate of less than one percent, the US continues to face racial and ethnic disparities in perinatal HIV infection that require ongoing commitment to eliminate them,” said the study’s senior author Xiong Jiang, PhD, an associate professor in the Department of Neuroscience at Georgetown University Medical Centre.
“Even more concerning are the gaps in the diagnosis and treatment of perinatal HIV infection in low and middle-income countries that are the result of disparities in access to care, procurement of antiretroviral drugs, suboptimal viral suppression particularly in young children, and high rates of significant co-morbidities like TB and malnutrition.”
To better understand the impact of perinatal HIV disease on cognitive development, in a meta-analysis study that was led by Sophia Dahmani from Georgetown University School of Medicine, the researchers analysed the results of nearly three dozen studies published between 2012 and 2023 that included more than 4 000 perinatally-infected HIV people, more than 2 300 HIV-exposed but uninfected people, and nearly 2 500 HIV-unexposed, uninfected people.
The investigators based their cognition analyses on neurological scores of the children when they reached an average age of around 11-years-old.
The study focused on test scores from three cognitive domains that tightly correlate with one another and play crucial roles in childhood development: executive function, which generates plans, solutions to problems, and organises structures that guide future action; working memory, which is how someone processes, uses and remembers information on a daily basis; and the speed at which someone processes information.
Compared with the two uninfected groups, perinatally HIV-infected children and adolescents had significant impairments in processing speed (a ‘Hedge’ score of -.64, where -.2 is a small effect, -.5 is a medium effect and -.8 is a large effect), working memory (-.69), and executive function (-.35).
Additional analyses suggested that the deficit for processing speed negatively correlated with a country’s gross national income (GNI) per capita – in other words, the lower the GNI per capita of that country, the more severely affected the processing speed for people with perinatal HIV living in that country.
“There are many ways to help children and adolescents with HIV to receive high quality education so that they can have constructive and independent lives,” said Jiang.
“The introduction of early childhood education programmes, academic accommodations whereby teachers provide more time during exams to account for reduced processing speeds, and caregiver training programmes could help improve the long-term cognitive and functional outcomes of these children and adolescents.”
The researchers said a future direction in this field would be to encourage better and bigger studies on perinatal HIV in more countries so that experts would not need to rely on combining multiple smaller studies for their analyses.
This would require collaborative efforts from the WHO, the United Nations and governments of both low to middle-income as well as high-income countries, they added.
Study details
Cognitive impairment in children and adolescents living with perinatal HIV disease in the ART era: a meta-analysis
Sophia Dahmani, Natella Rakhmanina, Xiong Jiang
Published in The Lancet eClinicalMedicine on 23 April 2024
Summary
Background
Despite improved survival and overall health outcomes from modern antiretroviral therapy (ART), children and adolescents with HIV face pervasive impairments in neurodevelopment including cognitive impairment, but there remains a lack of consensus on the cognitive domains that are affected in those children and adolescents. The objective of this meta-analysis was to evaluate the impact of perinatal HIV-infection on executive function, working memory, and speed of information processing in the ART era.
Methods
The PubMed database was searched for studies published between 1997 and 2024, plus additional search with the ScienceDirect, bioRxiv, and medRxiv databases. A meta-analysis was conducted on 35 studies published between 2012 and 2023 that encompassed a total of 4 066 perinatally-infected HIV patients, 2 349 HIV-exposed uninfected (HEU) controls, and 2 466 HIV-unexposed, uninfected (HUU) controls. Performance scores on executive function, working memory, and processing speed were pooled using random-effects meta-analysis.
Findings
Compared to HEU and HUU controls, perinatally HIV-infected children and adolescents presented with significant impairments in processing speed (Hedges g = −0.64, p < 0.00001), working memory (Hedges g = −0.69, p < 0.00001), and to a lesser degree, executive function (Hedges g = −0.35, p = 0.02). Meta-regression analysis suggested that the effect estimate of processing speed impairment negatively correlated with Gross National Income (GNI) per capita of the study countries (CALHIV vs HUU, p = 0.0016; CALHIV vs HEU, p = 0.0019), even though HIV-infected cases were compared to sociodemographically matched HUU controls from the same countries. Sub-group meta-analyses with participants from high-income or low-/middle-income countries provided further evidence suggesting that the performance gap between HIV-infected cases and HUU/HEU controls may be larger in low-/middle-income countries than high-income countries.
Interpretation
In the ART era, cognitive impairment (especially reduced processing speed and working memory) persists in children and adolescents living with HIV. These impairments may be more pronounced among those children and adolescents living with HIV in low-income countries, suggesting that there may be global health inequities in treatment outcomes with perinatal HIV-infection. However, meta-analysis and meta-regression analysis have their limitations, which calls for future collaborative multi-country international studies to directly investigate this important topic. Nevertheless, there is an unmet need to assure equity in timely assessments and interventions to optimise neurocognitive development and outcomes among children and adolescents with perinatal HIV globally.
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