Pretreatment levels of soluble cellular receptors and interleukin-6 are associated with HIV disease progression in subjects treated with highly active antiretroviral therapy - PubMed (original) (raw)

Pretreatment levels of soluble cellular receptors and interleukin-6 are associated with HIV disease progression in subjects treated with highly active antiretroviral therapy

Robert C Kalayjian et al. J Infect Dis. 2010.

Abstract

Background: To identify inflammatory pathways that may contribute to the pathogenesis of human immunodeficiency virus (HIV) disease, we explored associations between AIDS or death and different inflammatory markers, including selected soluble tumor necrosis factor superfamily receptors (sTNFRs) and ligands, interleukin (IL)-6, and CD8 T cell activation, in individuals treated with highly active antiretroviral therapy (HAART).

Methods: A case-control study of subjects in AIDS Clinical Trials Group (ACTG) protocols 384 and 5015, who were matched according to the CD4 cell count and plasma viral load at baseline, was performed using conditional logistic regression.

Results: Higher pretreatment concentrations of sTNFR-1, sCD27, sCD40L, and plasma IL-6 were associated with a new AIDS-defining illness or death in separate models adjusted for age, sex, hemoglobin, and the latest CD4 cell counts. In additional models that excluded case patients with opportunistic infections, sTNFR-1, sCD27, and sCD40L were each associated with a new AIDS-defining malignancy or death that developed at a median of 51 weeks after initiation of HAART, by which time the majority of subjects had a CD4 cell count of >200 cells/cm(3) and had achieved a plasma viral load of <50 copies/mL.

Conclusion: These data are compatible with a model in which these soluble inflammatory markers identify pathways that may contribute to the pathogenesis of HIV disease progression, pathways that might not be a direct consequence of ongoing HIV type 1 replication.

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Conflict of interest statement

Conflicts of Interest:

R.T.G. received grant funding from Tibotec and Gilead and an honorarium from GlaxoSmith Kline.

R.B.P. is on the Speaker’s bureau for Bristol Meyers Squibb and Gilead.

G.K.R. received grant funding from Gilead, Schering-Plough, and consulting fees from Abbott Laboratories, Boehringer Ingelheim Pharmaceuticals and Tibotec.

A.L. received honoraria from Abbott Laboratories and Bristol-Myers Squibb.

Figures

Figure 1

Figure 1

Kaplan-Meier plot depicting the onset of a CDC Category C clinical event or death among cases, by week after HAART-initiation.

Figure 2

Figure 2

Scatter/box plots of baseline immune activation markers among cases of opportunistic infection, and AIDS-associated malignancy or death, and their corresponding matched controls. The boxes encompass the upper and lower quartiles of the distribution of each variable, where the median value is represented by the line within each box. To facilitate comparisons between these markers, values of each variable were subtracted by their mean then divided by their standard deviation (z score). Trends and significant differences between cases and controls that were identified by multivariable models are indicated by the P-value for these differences.

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References

    1. Appay V, Sauce D. Immune activation and inflammation in HIV-1 infection: causes and consequences. J Pathol. 2008;214:231–41. - PubMed
    1. Eggena MP, Barugahare B, Okello M, et al. T cell activation in HIV-seropositive Ugandans: differential associations with viral load, CD4+ T cell depletion, and coinfection. J Infect Dis. 2005;191:694–701. - PubMed
    1. Erikstrup C, Kallestrup P, Zinyama-Gutsire RB, et al. Reduced mortality and CD4 cell loss among carriers of the interleukin-10 −1082G allele in a Zimbabwean cohort of HIV-1-infected adults. Aids. 2007;21:2283–91. - PubMed
    1. Fahey JL. Cytokines, plasma immune activation markers, and clinically relevant surrogate markers in human immunodeficiency virus infection. Clin Diagn Lab Immunol. 1998;5:597–603. - PMC - PubMed
    1. Giorgi JV, Lyles RH, Matud JL, et al. Predictive value of immunologic and virologic markers after long or short duration of HIV-1 infection. J Acquir Immune Defic Syndr. 2002;29:346–55. - PubMed

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