Late Language Emergence Risk in HIV-Exposed, Uninfected Infants: A Cautious Sigh of Relief

Since the advent of prenatal treatment to prevent mother-to-child HIV transmission, investigators have been concerned about the possibility of neurodevelopmental toxicity. The SMARTT studies were established to address this concern on an ongoing basis.

This study replicates findings that have been reported since early in the epidemic: Infants exposed to HIV but uninfected are at risk for early neurodevelopmental delays. Maternal alcohol or other substance use, maternal health, maternal cognitive function, and neonatal hyperbilirubinemia are noted as known risk factors. The observation that 20% to 30% of children who are exposed but uninfected experience late language emergence (LLE) is sufficient to support the recommendation for ongoing monitoring of neurodevelopmental function in all HIV-exposed children.

The other study findings — that in utero exposure to combination antiretroviral therapy is unrelated to LLE, and that atazanavir is associated with LLE at age 1 but not at age 2 — are reassuring. The use of a more sensitive measure at age 1 than at age 2 could explain lower detection and is a study-design limitation. Nonetheless, this report does provide evidence of an acceptable safety profile for HIV-exposed, uninfected infants at age 2. Although the long-term effects will not be fully defined until studies have been completed on these children in early adolescence, for now, these data support moving forward with current therapeutic strategies.