Keeping an eye on the brain of perinatally HIV-infected children

When the human immunodeficiency virus (HIV) first emerged in the 1980s, infection before, during, or shortly after birth (perinatal HIV-infection) frequently led to severe developmental delay, brain injury, or death before the age of two years. The virus causes a decrease of the CD4+ T-cells of the immune system, leaving the body without adequate defense against other illnesses such as infections, cancers, and brain inflammation. As of 1996, the combination of at least three antiretroviral drugs (combination antiretroviral therapy, or cART) has enabled suppression of HIV and reconstitution of CD4+ T-cells in blood. Since then, the survival and development of HIV-infected children has drastically improved. Nonetheless, perinatally HIV-infected children have poorer cognitive abilities than uninfected children. This thesis focuses on studying the potential mechanisms that could underlie cognitive impairment and cerebral injury in perinatally HIV-infected children who are adequately treated with cART.
This thesis supports the hypothesis that cognitive impairments, cerebral injury, and retinal thinning are not solely explained as static defects originating from a period of untreated HIV-infection in the past. In addition, ongoing damage may persistently occur despite suppressive antiretroviral treatment, with important roles for immune activation, inflammation, and vascular disease. This also implies that our current measures of adequate antiretroviral treatment – HIV suppression and sufficient CD4+ T-cell counts – may not reflect complete protection against the full spectrum of injury associated with HIV infection. It is therefore of high importance to continue monitoring perinatally HIV-infected children to increase our understanding of the neurocognitive effects of long-term exposure to HIV and antiretroviral treatment.