BackgroundHIV can spread into the central nervous system (CNS) early in the course of infection and this turns into intrathecal inflammation and neuronal damage. We aimed to investigate clinical and immunological parameters associated with elevated CSF VL in HIV‐infected ART‐naïve patients.Materials and MethodsHIV+ ART‐naïve patients underwent a comprehensive battery of neurocognitive (NC) tests and lumbar puncture (LP) for CSF HIV‐RNA detection. Plasma HIV‐RNA and peripheral T‐cell immune‐phenotypes (CD38/CD45RA/CD45R0/CD127 on CD4/CD8) were also assessed (flow cytometry). High‐CSF HIV RNA was defined as≥10000cp/mL (H‐CSF), while CSF HIV RNA<10000cp/mL characterized low VL patients (L‐CSF). Chi‐square and Mann‐Whitney tests were used. Parameters independently associated with CSF VL were explored by multivariate regression.ResultsA total of 131 patients were retrospectively enrolled. Forty‐two patients (32%) had CSF VL >10000 cp/mL.Table 1 shows the features of H‐ versus L‐CSF patients. Compared to L‐CSF patients, H‐CSF patients displayed lower current CD4+%, lower CD4/CD8 ratio and higher CD8%. No differences in NC tests performance were observed between groups (p=0.6). Regarding T‐cell immuno‐phenotypes, H‐CSF patients displayed a higher proportion of CD45R0+CD38+CD8+ (11 vs 7%, p=0.02) and lower expression of CD45RA+CD8+ % (16 vs 20%, p=0.007), in comparison to L‐CSF patients. In multivariate analysis CD45RA+CD8+ T‐cells % (OR 0.917, CI 95% 0.852–0.987, p=0.002) was associated with H‐CSF, even after adjustment for plasma VL, CD8 and CD4 count. Globally, in univariate CSF VL inversely correlated with CD45RA+CD8+ % (r=−0.223, p=0.0217) and CD127+CD4+ % (r= −0.204, p= 0.0225), while a positive association was found between CSF and plasma VL (r=0.303, p=0.0004) and CD8 % (r=0.211, p=0.016). In multivariate linear regression, in addition to positive association between plasma and CSF VL (β: 0.212, 95% CI 0.02–0.41, p=0.032), also CD45RA+CD8+ % were confirmed inversely associated to CSF VL (β: 0.21, 95% CI −0.5 to −0.002, p=0.036), adjusting for CD4/CD8 and CD4CD127 %.ConclusionsWe hereby describe a 32% prevalence of H‐CSF in a cohort of HIV+ ART‐naïve patients. Subjects with high‐CSF viral replication are mostly with higher systemic immune activation, in particular the percentage of naïve CD8 T‐cell is positively associated with CSF VL, irrespective of plasma VL. In HIV+ ART‐naïve patients, especially if featuring a hyperactivated T‐cell immune‐phenotype, lumbar puncture should be considered to further guide CNS‐targeted cART.
This thesis studies four web games that have been released in Estonia in 2004-2011 and have been sponsored by the Estonian Centre Party. Using video games in political campaigning is a recent and not very widely spread trend. Therefore, these web games provided an opportunity to examine the ways how political messages can be inserted into video games and how the qualities that are unique to video games can form political arguments and persuade the players. The main objective of this thesis was to identify the persuasive components of Centre Party's web games and to compare the persuasive arguments that were found from the games' representative layer to those that were formed on the games' procedural layer. In order to do that, the Centre Party's web games were placed in the wider context of political videogames and analyzed with semiotics, gameplay rhetoric and procedural rhetoric. Ultimately, the goal of the thesis is to emphasize the uniqueness of video game representative qualities which seem to be superseded by the studies of rhetorical potential of game rules