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Viro-immunological characterization of naïve patients with high cerebrospinal fluid (CSF) HIV RNA

Francesca Iannuzzi, Francesca Bai, Esther Merlini, Mattia Trunfio, Lidia Borghi, Teresa Bini, Antonella D'Arminio, Giulia Marchetti Carla


Background: HIV 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.
Material and Methods: HIV+ 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 test were used. Parameters independently associated with CSF VL were explored by multivariate regression.
Results: 131 patients were retrospectively enrolled. 42 pts (32%) had CSF VL > 10000 cp/ml. Table 1 shows the features of H- vs L-CSF patients. Compared to L-CSF patients, H-CSF pts 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, CI95% 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 (0.212, 95%CI 0.02-0.41, p=0.032), also CD45RA+CD8+ % were confirmed inversely associated to CSF VL ( -0.21, 95%CI -0.5- -0.002, p=0.036), adjusting for CD4/CD8 and CD4CD127 %.
Conclusions: we 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 immunephenotype, lumbar puncture should be considered to further guide CNS-targeted cART.

(Published: 2 November 2014)

Citation: Iannuzzi F et al. Journal of the International AIDS Society 2014, 17(Suppl 3):19710 |

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Journal of the International AIDS Society | eISSN 1758-2652 | Editors-in-Chief: Susan Kippax and Kenneth Mayer

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