Predictive value of serum biomarkers for response of limited-stage AIDS-associated Kaposi sarcoma to antiretroviral therapy with or without concomitant chemotherapy in resource-limited settings.

Guidelines for limited-stage human immunodeficiency virus-associated Kaposi sarcoma (AIDS/KS) recommend antiretroviral treatment (ART) as initial therapy. However, many such individuals show worsening KS and require additional chemotherapy. Methods to identify such patients are lacking. Setting: We studied whether serum levels of biomarkers associated with angiogenesis, systemic inflammation, and immune activation, which are elevated in HIV-infected individuals and implicated in the development of KS, could prospectively identify individuals with limited-stage AIDS-KS who would benefit from chemotherapy administered with ART. Methods: Serum specimens were obtained from participants in a randomized trial evaluating the value of adding oral etoposide chemotherapy ART in treatment-naïve people with limited-stage AIDS-KS in resource-limited settings. Serum biomarkers of inflammation (CRP, IL-6, IL-8, IL-10, G-CSF, sTNFR2), immune system activation (sIL2Rα, CXCL10/IP10, CCL2/MCP1) and angiogenesis (VEGF, MMP-2, MMP-9, endoglin, HGF) were measured at entry to determine whether baseline levels are associated with KS response. On-treatment changes in biomarker levels were determined to assess how etoposide modifies the effects of ART. Results: Pre-treatment CRP and IL-10 were higher in those whose KS progressed, and lowest in those who had good clinical responses. Pre-treatment CRP, IL-6 and sTNFR2 showed significant associations with KS progression at the week-48 primary endpoint. Immediate etoposide led to lower inflammation biomarker levels compared to ART alone. Early KS progression was associated with elevated pre-treatment levels of inflammation-associated biomarkers and increasing levels post-treatment. Conclusions: Quantifying serum biomarkers, especially CRP, may help identify persons with AIDS-KS who would benefit from early introduction of chemotherapy in addition to ART.