708 Predictive Value of Activated T-cells in Blood and Cerebrospinal Fluid for Cell-free Viral Load and HIV-1 Producing Cells in Both Compartments J. K. Neuenburg*1,2, E. Sinclair1, A. Nilsson1, R. W. Price1, R. M. Grant1,2 1Univ of California at San Francisco and 2Gladstone Inst of Virology and Immunology, San Francisco, CA
Background: HIV production in Cerebrospinal Fluid (CSF) is driven by systemic and local events, but it is unknown whether systemic or CSF inflammation/activation is driving CSF virus production. The objective of this study is to determine the relationship of CD4/CD8 T-cell activation in CSF and blood to the cell-free viral load and cell-associated viral load in both compartments.
Methods: Lymphocyte immunophenotyping by flow cytometry was performed on paired CSF/blood specimens. Infected T-cells were identified using the surface markers CD3+, CD14-, and cytoplasmic anti-p24-antibody. Activated cells were identified using the marker CD38. Viral loads (VL) were determined by RT-PCR (Roche). Multivariate statistical models accounted for repeated measures.
Results: We evaluated 37 paired blood/CSF specimens from 13 subjects for T-cell activation markers, cell-free viral load and HIV-antigen production. Median VL was 4.32 log10 copies/mL for plasma, 3.50 for CSF. HIV-1 p24-expression was detected in a median 0.82% of CSF T-cells and 0.33% of blood T-cells. The median fractions of CD4+ T-cells expressing CD38 were substantially higher: 31% in CSF and 43% in blood. Low CD4+ T-cell count in blood was the best predictor for p24% in CSF, independent of CSF white count and antiretroviral treatment. The CD38+CD4+ T-cell fraction in CSF was independently associated with VL in CSF and blood and the fraction of T-cells in CSF expressing p24. VL measurements were also associated with CD38+CD8+ cells in blood and CSF, but not with CD38+CD4+ cells in blood.
Conclusions: Activated CD4 cells in CSF have the best predictive value for cell-free viral load in blood and CSF and virus-producing cells in CSF, followed by activated CD8 cells in CSF, then activated CD8 cells in blood. Activated CD4 cells in blood hold the least predictive value for cell-free viral load in blood and CSF and virus-producing cells in CSF, possibly because of sequestration into tissue compartments or lymph nodes or because of consumption. Activated CD4+ T-cells in CSF-associated tissues may be consumed less rapidly than in lymphoid organs or other tissue compartments, possibly due to less cell-to-cell contact. We found that the majority of activated T-cells in both compartments are not expressing viral antigens. End-stage disease (with high viral load and low blood CD4+ T-cell counts) may involve increased trafficking of activated CD4+ T-cells (infected and not-infected) from blood into tissues, including lymph nodes and CSF.