Central nervous system and neurodevelopmental outcomes of HIV + and HIV exposed children: A mini review of recent findings and lessons learned from the field

Abstract

• There has been an increase in research looking at neurodevelopmental/neurologic outcomes of children living with HIV (Children LWHIV) and HIV exposed but uninfected children (HEU) during an era of ART. This Neurodevelopmental mini review presents recent research findings on the neurodevelopmental outcomes for children LWHIV and HEU children based on literature published since 2015. The research was conducted in diverse settings: both in resource rich settings such as the U.S and Europe; as well as resource limited international settings with a focus on Africa. • Prior to the availability and wide scale roll out of antiretroviral drugs (ARVs) for both treatment and prevention, about one in four infants born to mothers living with HIV became infected, with transmission occurring either in utero , during labor/delivery or through breastfeeding. For children LWHIV, a large proportion demonstrated early findings of HIV related encephalopathy including delay in acquisition of normal mental and motor milestones, as well as neurologic findings including microcephaly, hypotonia, and diplegia. Overall survival was also extremely poor, with 50% of HIV + children diagnosed with HIV/AIDS not surviving past 5 years of age. However, In resource rich settings since the late 1990′s; and internationally from the early 2000′s forward, there has been much progress with roll out of combination highly effective antiretroviral therapy (ART) for both prevention of mother to child transmission and maternal treatment; as well as early infant diagnosis of HIV among infants followed by early treatment. This has resulted in many fewer cases of HIV + children with severe HIV/AIDS related encephalopathy. • However, studies since then have shown that children and adolescents LWHIV as a group, even with effective early ART, demonstrate median lower overall neurocognitive scores on standard neurocognitive testing when compared to HIV exposed but uninfected (HEU) children or HIV Unexposed uninfected (HUU) children born to women who were HIV negative. They also demonstrated lower average scores on specific developmental testing subdomains such as receptive language, visual reception and/or attention. The HIV + children and adolescents were also at increased risk for repeating academic grades compared to HEU or HUU children from similar backgrounds. • In regards to HEU uninfected children, published findings continue to be mixed, with some studies reporting lower scores on attention, receptive and expressive language compared to HUU children born to HIV negative mothers, from similar socioeconomic backgrounds. Reassuringly there is no evidence that early exposure to combination antiretovirals in utero or during breastfeeding has led to any adverse developmental outcomes compared to exposure to single drugs used of prevention of mother to child transmission of HIV during pregnancy or during breastfeeding. • Exciting new research directions include early neurodevelopmental testing to identify those HIV + and HEU children most at risk for developmental delays; as well as early caretaker interventions in the home setting and with use of “computer brain” game interventions to optimize neurocognitive development of at risk children LWHIV and HEU children in both resource rich and resource limited settings. Future research will need to focus on later academic outcomes among adolescents LWHIV and HEU children.