HIV and the Brain: Cognitive comorbidities and complications in HIV infection and treatment

This thesis focusses on cognitive decline in HIV infection, of which the different forms are summarized under the term HIV-Associated Neurocognitive Disorder (HAND). The different parts of the thesis discuss separate aspects of HAND, like the effect of combination antiretroviral therapy (cART) on its etiology, the prevalence of HAND in Western and resource-limited settings, how to screen for HAND, and challenges in diagnosing it. Finally, the use of a novel diagnostic instrument, blood oxygenated level dependent functional MRI (BOLD fMRI) is investigated. The main findings of this thesis are that some types of antiretroviral therapy, and then especially Efavirenz, have a negative effect on cognition even in asymptomatic patients. Moreover, discontinuing this drug can significantly improve cognitive functioning. Furthermore, we found a high prevalence of cognitive decline in a Dutch HIV-positive outpatient population as well as in a South-African urban population. We tried to find a suitable screening tool for the latter, but were unsuccessful. However, we were successful in developing a protocol for which steps to take after a positive screening, and evaluated a possible treatment for HAND; cognitive rehabilitation. Finally, we summarized the research on BOLD fMRI and HIV in a systematic review.