OBJECTIVES-Pediatric HIV infection is a growing problem in most regions of the world. Data on the effects of HIV on the neurodevelopment of children in resource-poor settings are scarce but necessary to guide interventions. The purpose of this study was to compare the neurodevelopment of preschool-aged HIV-infected, HIV-affected (HIV-uninfected AIDS orphans and HIV-uninfected children whose mother had symptomatic AIDS), and healthy control children in Kinshasa, Democratic Republic of Congo. METHODS-Thirty-five HIV-infected, 35HIV-affected, and 90 control children aged 18 to 72 months were assessed by using the Bayley Scales of Infant Development II, Peabody Developmental Motor Scales, Snijders-Oomen Nonverbal Intelligence Test, and Rossetti Infant-Toddler Language Scale, as appropriate for age.RESULTS-Overall, 60% of HIV-infected children had severe delay in cognitive function, 29% had severe delay in motor skills, 85% had delays in language expression, and 77% had delays in language comprehension, all significantly higher rates as compared with control children. Young HIV-infected children (aged 18-29 months) performed worse, with 91% and 82% demonstrating severe mental and motor delay, respectively, compared with 46% and 4% in older HIV-infected children (aged 30-72 months). HIV-affected children had significantly more motor and language expression delay than control children.CONCLUSIONS-The impact of the HIV pandemic on children's neurodevelopment extends beyond the direct effect of the HIV virus on the central nervous system. AIDS orphans and HIVnegative children whose mothers had AIDS demonstrated significant delays in their neurodevelopment, although to a lesser degree and in fewer developmental domains than HIVinfected children. Young HIV-infected children were the most severely afflicted group, indicating the need for early interventions. Older children performed better as a result of a "survival effect," with only those children with less aggressive disease surviving.

No abstract

HIV-1 subtype B replication in the CNS can occur in CD4+ T cells or macrophages/microglia in adults. However, little is known about CNS infection in children or the ability of subtype C HIV-1 to evolve macrophage-tropic variants. In this study, we examined HIV-1 variants in ART-naïve children aged three years or younger to determine viral genotypes and phenotypes associated with HIV-1 subtype C pediatric CNS infection. We examined HIV-1 subtype C populations in blood and CSF of 43 Malawian children with neurodevelopmental delay or acute neurological symptoms. Using single genome amplification (SGA) and phylogenetic analysis of the full-length env gene, we defined four states: equilibrated virus in blood and CSF (n = 20, 47%), intermediate compartmentalization (n = 11, 25%), and two distinct types of compartmentalized CSF virus (n = 12, 28%). Older age and a higher CSF/blood viral load ratio were associated with compartmentalization, consistent with independent replication in the CNS. Cell tropism was assessed using pseudotyped reporter viruses to enter a cell line on which CD4 and CCR5 receptor expression can be differentially induced. In a subset of compartmentalized cases (n = 2, 17%), the CNS virus was able to infect cells with low CD4 surface expression, a hallmark of macrophage-tropic viruses, and intermediate compartmentalization early was associated with an intermediate CD4 entry phenotype. Transmission of multiple variants was observed for 5 children; in several cases, one variant was sequestered within the CNS, consistent with early stochastic colonization of the CNS by virus. Thus we hypothesize two pathways to compartmentalization: early stochastic sequestration in the CNS of one of multiple variants transmitted from mother to child, and emergence of compartmentalized variants later in infection, on average at age 13.5 months, and becoming fully apparent in the CSF by age 18 months. Overall, compartmentalized viral replication in the CNS occurred in half of children by year three.

No abstract

Objective To assess the effect of HIV care (including HAART if eligible) on neurodevelopment. Design Prospective cohort study Methods Motor and mental development of 35 HIV-infected children (age 18-71 months) was assessed at entry into care, and after 6 and 12 months using age-appropriate tools. Developmental trajectory was compared to 35 HIV-uninfected, affected and 90 control children using linear mixed effects models. Effects of age (≤ or >29 months) and timing of entry into care (before or after HAART eligibility) were explored in secondary analyses. Results At baseline, HIV-infected children had the lowest, control children the highest, and HIV-uninfected affected children intermediate mean developmental scores. After one year of care, HIV-infected children achieved mean motor and cognitive scores that were similar to HIV uninfected, affected children although lower compared to control children. Overall, HIV-infected children experienced accelerated motor development but similar gains in cognitive development compared to control children. Exploratory analyses suggest that younger children and those presenting early may experience accelerated greater gains in development. Conclusions HIV-infected children accessing care experience improved motor development, and may, if care is initiated at a young age or an early stage of the disease, also experience gains in cognitive development.