[19]IMMUNE ACTIVATION IS A MAJOR CAUSE FOR CD4 DECLINE DURING HIV IMMUNE ACTIVATION IS A MAJOR CAUSE FOR CD4 DECLINE DURING HIV ] IMMUNE ACTIVATION IS A MAJOR CAUSE FOR CD4 DECLINE DURING HIV

1st International AIDS Society Conference on HIV Pathogenesis and Treatment

Buenos Aires, Argentina - July 8-11, 2001

[TITLE:] IMMUNE ACTIVATION IS A MAJOR CAUSE FOR CD4 DECLINE DURING HIV INFECTION;BETTER CORRELATION OF IMMUNE ACTIVATION MARKERS THAN HIV PLASMA VIRAL LOAD TO CD4 LEVELS

[AUTHOR(S):] Bentwich Z, Kalinkovich S, Leng Q, Weissman Z, Borkow G
Hebrew University Hadassah Medical School, Rehovot, Israel

IAS Conf HIV Pathog Treat 2001 Jul 8-11;1st: Abstract No. 19

[ABSTRACT:] Objectives: Study the role of T-cell immune activation and proliferation and HIV-1 plasma viral load (VL) in determining CD4+ T-cell levels during HIV-1 infection.

Methods: 54 HIV infected patients ( 35 undergoing antiretroviral treatment(HAART) and 19 without such treatment), were studied. Peripheral blood T cell subsets, HIV plasma viral loads, immune activation markers (HLA-DR, CTLA-4, Ki67, and CD38) by flowcytometry,and cell proliferation, were studied sequentially.

Results: Decrease in CD4 levels and CD4/CD8 ratios, and increase in CD8 levels, in both treated and untreated HIV(+) individuals, was very strongly correlated with immune activation (log %HLA-DR+CD3+ cells; r=-0.78, -0.77 and 0.58, respectively; p<0.0001), moderately to CD4 T-cell proliferation (log %Ki-67+CD4+ cells; r=-0.57 (p<0.0001), -0.48 (p<0.001) and 0.37 (p<0.01), respectively), and only weakly to VL (r=-0.36 (p<0.01), -0.23 (p=0.09), 0.13 (p=0.35), respectively). Almost half(48%) of CD4+Ki67+ cells also expressed CTLA-4 , and there was a significant inverse correlation between CTLA-4 and CD28 expression, and between CTLA-4 expression and cell proliferation.

Conclusions: 1) Immune activation is a major determinant of CD4 decline, and should therefore become central in monitoring HIV infection, and outcome of antiviral treatment. 2) The correlation of CD4 levels to Ki-67 expression is only partially related to cell proliferation, and more likely represents immune activation. 3) The upregulation of CTLA-4 during HIV infection represents an imprortant pathway of T cell activation which may freeze cells in G1 phase, prevent their proliferation, and lead to varying degrees of anergy. 4) These results support the notion that the major cause of the deterioration and dysfunction of the immune system during HIV infection is the chronic immune activation caused by HIV.

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