Our study demonstrated that school-aged HIV-infected children have low cognitive function, with 79% having below normal intelligence quotient. We found that HIV-infected children had lower cognitive function compared to age-matched HIV-affected and normal children. After receiving antiretroviral treatment for average of 3 years, there was no improvement in cognitive function.
Several reports have shown low cognitive function among school-aged HIV-infected children.8,11,13
The mean IQ among HIV-infected Thai school-aged children in this study is 79 (SD 13), which is slightly lower than report from a large study among U.S. children with a mean IQ of 84 (SD 15).8
However, in the U.S. study, the children had better immunologic status with average CD4 of approximately 690
cells. The study among U.S. HIV-infected and HIV-affected school-aged children focused on the receptive language ability, which is highly correlated with IQ score, found that the HIV infected group had significany lower score than HIV-affected group (mean score of 83.8 versus 87.6).11
The recently reported data among 58 Thai HIV-infected children with median age of 7 years and median CD4 percentage of 20 showed a median (IQR) of IQ of 72 (65–84).13
The poor neurocognitive function in school-aged HIV-infected children might be explained by many reasons. First, HIV infection may have a direct effect on neurodevelopment during the first few years of life, which is the time of rapid brain development, or it may have an indirect effect through recurrent infections or opportunistic, leading to poorer general health. A study among HIV-infected infants from Tanzania showed that infants with in utero infection had higher risk of delayed mental functioning compared to infants who were diagnosed at a later stage of life.3
Another study among HIV-infected children from the United States showed that higher plasma viral load greater than 50,000 copies per milliliter was correlated with poorer cognitive outcome.8
A second factor that might contribute to poor neurocognitive oucome is low socioeconomic status, which could lead to a variety of obstacles hindering effective child rearing, such as inadequate food, lack of time for cognitively stimulating activities, and poor parent–child relationships as a result of stress14
. In our study, HIV-infected children lived in families with lower socioeconomic status than the control group. Third, family structure also plays an important role in child development. In our study, 75% of HIV-infected children were raised by their grandparents and other relatives, which is consistent with other studies (26%–56%),15–17
while 73% of HIV-affected and almost all normal controls lived with their parents. A study in non-HIV–infected Thai children showed that children reared by grandparents were at higher risk of having developmental delay than those reared by their parents.18
A U.S. study (PACTG 338) also reported that children living with their biological parents were less likely to manifest conduct or learning problems when compared to those living with others.19
Nevertheless, in the multivariate logistic analysis which adjusted for the socioeconomic status and family structure, the HIV-infected children still had higher odds of having poor cognitive function compared to controls.
Several studies have shown that neurocongitive function does not improve after receiving antiretroviral therapy.6,8
In our study, the cognitive function among HIV-infected children was not improved after received NNRTI-based ART for 3 years, despite majority of children had undetectable viral load and normal CD4
cell. This is similar to previous reports by Jeremy et al.8
that showed only minor improvement in neuropsychological functioning after 48 weeks on protease inhibitor-based ART. A study among South African children who had a median age of 5 years, also reported no improvement in neurocognitive function after 6 months of ART. This might be explained by the timing of neurodamage which is likely to occur very early in life and is not easily corrected. This leads to a possible research question of whether starting ART earlier during infancy period will improve neurocognitive outcome in HIV-infected children.
The second cognitive assessment showed decline in verbal IQ but not performance IQ for all groups. The information and comprehension subtests were the two domains in which there were significantly lower scores in the second assessment across all groups of children. This may be explained by the lack of cultural sensitivity or language barrier of assessment tools on the verbal part. The limitation of the test was more prominent in the second assessment because children were getting older and were tested with more question items. The other possible explanation for the decline in verbal IQ in the second assessment are the interpersonal variability of the psychologists. However, since the result of performance IQ is consistent between first and second assessments, we therefore believe that it is not a case.
The strength of our study is that it is the first prospective long-term follow-up study of neurocognitive outcome in Asian HIV-infected children. The study design has included age-matched HIV-affected children and normal control groups. There are several limitations to this study. First of all, there was no baseline data for IQ scores prior to ART initiation, so we could not assess the effect of antiretroviral therapy, especially during the first 6 months of treatment. Second, we did not collect information on school performance and social functioning from the subjects' schoolteachers because of the families' needs to maintain confidentiality about participating in the study. Third, the WISC-III instrument being translated into the Thai language may have been a cause of the lower cognitive score. However, given the results in the control group, we are confident that the poor cognitive function found in HIV-infected children is valid. Fourth, the HIV-infected children in this study were born when antiretroviral therapy was not widely available in Thailand. Therefore, they had advanced disease; more than half had experienced clinical category B and C symtoms and had very low nadir CD4 % prior to receive treatment. The findings might be bias toward severely poor cognitive function.
Currently, in medical practice we focus on clinical, immunologic, and virologic criteria to start ART and also to monitor the effectiveness of treatment in HIV-infected patients. However, for children who are infected with the HIV virus during the period of brain development, the neurocongitive aspect should be considered as a factor to consider for early initiation of ART, especially in infants and young children. The findings in this study indicate that school-aged children with HIV infection experience difficulties with their living and social functioning when compared with peers of the same age without a chronic illness. There is a need for future research to develop strategies to improve intellectual and school performance in this population.