Achieving Optimal Neurodevelopmental Outcomes in HIV-Infected Infants

Human immunodeficiency virus (HIV)-infected infants who achieve viral suppression from antiretroviral therapy (ART) are more likely to partially recover developmental milestones but with persistent deficits compared to uninfected infants, according to an African study published in BMC Pediatrics.1

Previous studies conducted in US cohorts in presymptomatic infants diagnosed with HIV showed better virologic responses to ART were associated with improved achievement of developmental milestones but were still below national averages in noninfected infants.2-6 As more than 90% of neonatal HIV infections occur in sub-Saharan regions of Africa, where diagnosis does not usually occur until after symptom onset,7-10 the investigators focused on an HIV population from Kenya who were symptomatic prior to receiving ART.

A total of 73 HIV-infected infants taking ART (median age 3.7 months) were followed prospectively in comparison to a control group of 92 HIV-unexposed uninfected (HUU) infants (median age 1.6 months), all identified at maternal health clinics or hospitals in Nairobi, Kenya. HIV-infected infants who reached virologic suppression and immune recovery at 6 months showed delays in speech development of approximately 2 months (P =.002), while infants who did not have good response to ART had even greater delays of 5 months (P <.0001). A trend toward a 2-month delay in walking without support at 6 months in the ART-responsive infants increased to 4 months in non-ART-responsive infants.

“Although scores for some domains improved, in general children had scores below a regional norm population after 6 months of ART,” explained lead investigator Sarah Benki-Nugent, MS, PhD, of the department of global health at the University of Washington in Seattle. When asked if improvement in development was likely to continue, she responded, “Some children may catch up, but several factors, including the child’s HIV disease severity before starting treatment, the timing of treatment, his or her nutritional status, and the child’s home environment and future schooling are also likely very important determinants.”

At the time of enrollment, HIV-infected infants were older than HUU infants by an average of 2 months. They had a median CD4 percentage of 18%, 41.1% (30 patients) had World Health Organization (WHO) stage 3 or 4 HIV, and 52.1% (38 patients) had already been hospitalized. The investigators hypothesized that incomplete recapture of developmental milestones despite effective ART responses may have been related to infectious infiltration of the central nervous system prior to treatment or to incomplete viral clearance after treatment.

These findings support previous research showing that early intervention is the most important factor in retaining cognitive and motor development.11,12 “Altogether, these studies suggest that it is critical to provide additional strategies, such as parenting support for early childhood development, alongside HIV treatment, to help children reach their full potential,” Dr Benki-Nugent said.

“Early HIV diagnosis and treatment is likely the best strategy for achieving optimal neurodevelopmental outcomes in HIV-infected children,” Dr Benki-Nugent reported. “In our study, infants who had robust responses to ART had better outcomes. We have observed similar findings in Kenyan hospitalized HIV-infected children with a new diagnosis and who were aged 0-5. Thus, it is critical for community providers and leaders to understand the potential benefits of early HIV treatment for preserving brain development, and the importance of prompt HIV testing during infancy.”

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