Impact of the HIV Tat C30C31S dicysteine substitution on neuropsychological function in patients with clade C disease

Previous animal studies have identified a C31S residue substitution in the C30C31 dicysteine motif of the Tat protein that is associated with reduced neurovirulence in clade C HIV. However, clinical studies of patients infected with clade C HIV have reported significant levels of cognitive impairment. To date no study has specifically examined cognitive function in clade C-infected patients as a function of the presence or absence of the Tat C31 substitution. The present study investigated the impact of the Tat C30C31S genetic substitution among individuals residing in South Africa infected with clade C HIV that either exhibited the C30C31 motif (n = 128) or the C31S motif (n = 46). A control group of seronegative individuals were included to examine the overall impact of HIV on cognitive performance. All individuals completed a comprehensive neuropsychological battery consisting of tests sensitive to HIV. Results revealed that clade C-infected individuals performed significantly worse across cognitive tests compared to seronegative controls. However, there were no significant differences in cognitive performances between individuals with the C31S motif versus those without the C31S substitution. Proximal CD4 cell count and plasma viral load were unrelated to cognitive performances for either group. Results confirm that the C31S dicysteine motif substitution of the Tat protein does not appreciably moderate neuropsychological outcomes in clade C. Further, these findings highlight the importance of clinical management of cognitive symptoms among individuals infected with this viral clade worldwide

The Role of Medical Imaging in Defining CNS Abnormalities Associated with HIV-Infection and Opportunistic Infections

In this review of the current literature, we examine the role of medical imaging in providing new and relevant information on central nervous system (CNS) injury associated with human immunodeficiency virus (HIV) infection and various clinical manifestations of this injury. Common imaging modalities used to examine CNS injury in HIV infection include structural magnetic resonance imaging, magnetic resonance spectroscopy, diffusion tensor imaging, functional MRI, and positron emissions tomography. Clinical implications for the findings are discussed for each of these modalities individually and collectively. In addition, the direction for future studies is suggested in an attempt to provide possible methods that might answer the many questions that remain to be answered on the evolution and progression of CNS injury in the context of HIV infection