A Plasma Biomarker Signature of Immune Activation in HIV Patients on Antiretroviral TherapyReport as inadecuate




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Background

Immune activation is a strong predictor of disease progression in HIV infection. Combinatorial plasma biomarker signatures that represent surrogate markers of immune activation in both viremic and aviremic HIV patients on combination antiretroviral therapy cART have not been defined. Here, we identify a plasma inflammatory biomarker signature that distinguishes between both viremic and aviremic HIV patients on cART and healthy controls and examine relationships of this signature to markers of disease progression.

Methods

Multiplex profiling and ELISA were used to detect 15 cytokines-chemokines, soluble IL-2R sIL-2R, and soluble CD14 sCD14 in plasma from 57 HIV patients with CD4 nadir <300 cells-µl and 29 healthy controls. Supervised and unsupervised analyses were used to identify biomarkers explaining variance between groups defined by HIV status or drug abuse. Relationships between biomarkers and disease markers were examined by Spearman correlation.

Results

The majority 91% of HIV subjects were on cART, with 38% having undetectable viral loads VL. Hierarchical clustering identified a biomarker cluster in plasma consisting of two interferon-stimulated gene products CXCL9 and CXCL10, T cell activation marker sIL-2R, and monocyte activation marker sCD14 that distinguished both viremic and aviremic HIV patients on cART from controls p<0.0001 and were top-ranked in variables important in projection plots. IL-12 and CCL4 were also elevated in viremic and aviremic patients compared to controls p<0.05. IL-12 correlated with IFNα, IFNγ, CXCL9, and sIL-2R p<0.05. CXCL10 correlated positively with plasma VL and percentage of CD16+ monocytes, and inversely with CD4 count p = 0.001, <0.0001, and 0.04, respectively.

Conclusion

A plasma inflammatory biomarker signature consisting of CXCL9, CXCL10, sIL-2R, and sCD14 may be useful as a surrogate marker to monitor immune activation in both viremic and aviremic HIV patients on cART during disease progression and therapeutic responses.



Author: Anupa Kamat, Vikas Misra, Edana Cassol, Petronela Ancuta, Zhenyu Yan, Cheng Li, Susan Morgello, Dana Gabuzda

Source: http://plos.srce.hr/



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