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A systematic literature review examining soluble and cellular biomarkers in HIV patients receiving antiretroviral therapy

M Byrnes, K Travers, M Burns, S Sapra


The use of antiretroviral therapies (ART) for treatment of human immunodeficiency virus type 1 (HIV-1) has led to more favorable prognoses for infected individuals, including reduced HIV viral load, improved CD4+ T-cell recovery, and slower disease progression. However, ART-treated HIV+ patients may have increased risk of adverse outcomes associated with chronic inflammation and immune activation. Molecules associated with chronic immune system activation and inflammatory cytokine production may be useful biomarkers of HIV pathogenesis and/or ART outcomes. We systematically identified MEDLINE-indexed articles published in the past decade investigating the association of several soluble (IL-6, CRP, MCP-1, IP-10, D-dimer, soluble CD14, and LPS) and cellular (CD28, CD38, HLA-DR, PD-1, caspase-3, IFNγ and IL-2 ELISpots) biomarkers with clinical outcomes in ART-treated HIV positive (HIV+) patients. Seventy publications were included, consisting mainly of observational studies of soluble biomarkers. One quartile elevations in baseline IL-6, CRP, and D-dimer were associated with increased risk of disease progression or death (ORs 1.8-2.4; p≤0.01) and all-cause mortality (ORs 4.1-5.3; p≤0.0001); these elevations were also associated with increased rates of IRIS (ORs 1.59-2.07; p≤0.001). Additionally, IL-6, CRP, and D-dimer levels were higher in patients who experienced a cardiovascular event than in controls (p≤0.001). The association between soluble biomarkers and quantitative assessments of HIV viral load has not been studied as thoroughly. However, several studies found an association between D-dimer and viral load. Research is lacking regarding the relationship between CD4 count and soluble biomarkers. Most studies evaluating cellular biomarkers examined their association with HIV viral load and CD4 count, but did not examine clinical outcomes. The most commonly studied cellular biomarkers were the T cell activation markers CD38 and HLA-DR. Studies suggest that CD4 and CD8 activation were increased in patients with higher HIV viral load, and that CD8 activation was higher in patients with low CD4 counts. In our review, we found that several soluble biomarkers were related to the risk of adverse clinical outcomes in ART-treated HIV+ patients. More data, particularly regarding cell-associated biomarkers, is required to characterize their association with outcomes of interest, to describe causality, and to document their prognostic importance.

(Published: 11 November 2012)

Citation: Abstracts of the Eleventh International Congress on Drug Therapy in HIV Infection

Byrnes M et al. Journal of the International AIDS Society 2012, 15(Suppl 4):18172 |

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