Serum Biomarkers in Advanced-Stage AIDS-Associated Kaposi Sarcoma in Resource Limited Settings

Abstract

Background: We investigated whether serum levels of biomarkers of inflammation, immune activation and angiogenesis, which have been implicated in the pathogenesis of Kaposi sarcoma (KS), were associated with tumor burden and treatment response of advanced AIDS-KS. Methods: Participants with advanced, previously untreated AIDS-KS enrolled in AMC066/ACTG A5263, a prospective, randomized trial conducted in sub-Saharan Africa and South America, were randomly assigned to either paclitaxel (PTX)+ART or bleomycin/vincristine (BV)+ART. Biomarkers of inflammation (CRP, IL-6, IL-8, IL-10, G-CSF, sTNF-RII), immune activation (sCD25/sIL-2Rα, CXCL10/IP-10, CCL2/MCP1), and angiogenesis (MMP-9, soluble endoglin, VEGF, MMP-2 and HGF),were measured by Luminex to determine whether pre- or post-treatment levels were associated with KS response and tumor burden. Wilcoxon rank-sum tests were used to compare biomarkers levels between groups. Results: 131 participants met the analysis inclusion criteria (70 PTX, 61 BV; 82 non-progressors, 49 progressors). Higher baseline KS tumor burden was associated with higher pre-treatment inflammatory and immune activation biomarker levels, and lower levels of markers with angiogenesis-inhibitory activity. Associations of baseline biomarker levels with subsequent KS response were not observed, however, progressors showed higher levels of several markers of inflammation and immune activation (IL-6, IL-10, sTNF-RII and IP-10) than non-progressors at weeks 3 and 12. Conclusions: Pre-treatment biomarker levels were associated with greater KS tumor burden but not with KS response to chemotherapy + ART in people with advanced AIDS-KS. Differential levels of several serum biomarkers were noted on treatment in progressors and non-progressors, suggesting that increased tumor burden was associated with higher levels of inflammation and immune activation.