Antiretrovirals Linked to Worse Neurodevelopment in Young Kids

Children exposed to antiretrovirals (ARVs)-those who are HIV-positive as well as those exposed to HIV in utero but who remain uninfected-may have worse neurodevelopmental outcomes than children never exposed to ARVs.

This is the key finding in the first quantitative meta-analysis of neurodevelopment in young children exposed to HIV and/or ARVs.¹ The study, published in Pediatrics, also showed that HIV-positive children as well as those exposed to HIV but HIV-negative had worse cognitive and motor development than children never exposed to HIV.

The results may help inform treatments and interventions designed to improve neurodevelopment in HIV- and ARV-exposed children in early childhood, when the brain is most receptive to intervention.

“Determining if and how either ARV or HIV exposure adversely affects neurodevelopment in HIV-negative children emerges as a key priority,” wrote first author Megan McHenry, MD, MS, of Indiana University (Indianapolis, IN) and Moi University (Eldoret, Kenya), and colleagues.

The authors stressed that research does not definitively point to negative effects of ARVs on cognitive development in children, and that these results should be interpreted with caution. More research is needed to determine the impact of ARV exposure on neurodevelopment in children.

Research has shown that children with HIV have worse neurodevelopment than children without HIV. Increasingly, however, children exposed to HIV in utero are treated with ARVs, creating a growing population of children exposed to HIV and ARVs who subsequently do not become infected with HIV. However, little is known about neurodevelopmental outcomes in this group.

To explore the issue, researchers searched 5 databases for studies about children under age 8 and published mostly in English between January 1990 and January 2017.

The systematic review included 45 studies (most from the US and Canada), and the meta-analysis included 11 studies (mostly from the US and Sub-Saharan Africa). The meta-analysis focused on studies that used the Bayley Scales of Infant and Toddler Development to assess neurodevelopment.

The review revealed notably impaired cognitive and motor development among HIV-positive children. A few studies (n=3) also showed that these factors were also impaired in HIV-exposed but uninfected children. Severe cognitive delays in HIV-positive children ranged from 21%-35% in HIV+ children, 1%-31% for HIV-exposed, uninfected children, and 1%-15% for HIV-unexposed, uninfected children. Severe motor delays ranged from 21%-66% in HIV-positive children vs 0%-39% in HIV-exposed, uninfected children, and 0%-6% in HIV-unexposed, uninfected. 

Key results of the meta-analysis:
• Motor development index, (vs HIV-unexposed, uninfected):
  o HIV-exposed, uninfected: -6.61
  o HIV-positive: -16.32
• Psychomotor developmental index (vs HIV-unexposed, uninfected):
  o HIV-exposed, uninfected: -4.25
  o HIV-positive: -17.62
• Exposed to ARVs (vs HIV-unexposed, uninfected):
  o Motor development index: HIV-exposed, uninfected (-10.00) and HIV-positive (-20.26)
  o Psychomotor developmental index: HIV-exposed, uninfected (-5.54) and HIV-positive (-19.42)
• Not exposed to ARVs (vs HIV-unexposed, uninfected):
o Motor development index: HIV-exposed, uninfected (+0.95) and HIV-positive (-7.82)
o Psychomotor developmental index: HIV-exposed, uninfected (-1.15) and HIV-positive (-12.70)

The authors noted that results varied based on the quality of the study. In high quality assessments, cognitive and motor scores were similar for HIV-exposed, uninfected children and HIV-unexposed, uninfected children. In low quality studies, HIV-exposed, uninfected children had worse cognitive and motor development than HIV-unexposed, uninfected children. HIV-positive children had lower scores regardless of the quality of the study.

They explained that many of the tests used to assess neurodevelopment were not adapted for the local population. Thus, they proposed an international standard for assessing early childhood neurodevelopment that can be used across cultures and in different settings. Such tests may help scientists reach a more definite conclusion about whether ARVs negatively impact neurodevelopment in young children.

Take Home Points
• First quantitative meta-analysis of neurodevelopment in young children exposed to HIV and/or ARVs showed that HIV-positive children and those exposed to HIV but uninfected have worse neurodevelopmental outcomes than children never exposed to ARVs
• Children with HIV and those exposed to HIV but uninfected had worse cognitive and motor development than children unexposed and uninfected with HIV
• Results regarding worse neurodevelopment with ARV-exposure should be interpreted with caution due to differences in study quality; further studies are needed

References:

1. McHenry MS, McAteer CI, Oyungu E, et al. Neurodevelopment in Young Children Born to HIV-Infected Mothers: A Meta-analysis. Pediatrics. 2018;141(2):e20172888.