Blood cytokine levels predict treatment response and survival in HIV-linked Kaposi sarcoma

Baseline levels of immune-signalling molecules in the blood can help predict how patients with HIV-associated Kaposi sarcoma respond to treatment and how long they survive, according to a new study published in AIDS Research and Therapy. The findings, drawn from a randomised clinical trial in a region where the cancer remains a major cause of illness and death, suggest that routine cytokine measurements could eventually help clinicians identify patients at highest risk before therapy begins.

Kaposi sarcoma is a cancer caused by Kaposi sarcoma herpesvirus, also known as human herpesvirus 8, and it is strongly associated with HIV infection. Cytokines, small signalling proteins that coordinate immune responses, are known to be dysregulated in the disease and are considered central to its development. However, their value as biomarkers for predicting clinical outcomes has remained unclear, which is the question the research team set out to address.

The study analysed baseline serum samples from 73 participants who had not yet received either antiretroviral therapy or chemotherapy. Most had advanced HIV-associated Kaposi sarcoma. Participants had been randomised in the underlying trial, registered as NCT00380770, to receive antiretroviral therapy either alone or combined with chemotherapy. The researchers used a Milliplex multiplex platform to measure concentrations of 28 different cytokines in each sample.

Statistical analysis linked specific cytokine patterns to distinct clinical features. Lower concentrations of MIP-1β, a chemokine involved in immune cell recruitment, were associated with poorer baseline immune status, defined as CD4 cell counts below 150, with a p-value of 0.04. This suggests that diminished levels of this signalling molecule tracked with more advanced immune suppression at the start of the study.

Eotaxin, another immune-signalling protein, showed a clear relationship with how patients fared on treatment. Higher eotaxin concentrations were associated with poorer clinical response. Median levels were highest in patients whose disease progressed, at 112.6 picograms per millilitre, followed by those with stable disease at 83.8 picograms per millilitre, and were lowest in patients who achieved an overall response, at 68.8 picograms per millilitre. The overall association was statistically significant, with a p-value of 0.04.

Two proinflammatory cytokines stood out in survival analysis. Higher levels of interleukin-6 and interleukin-8 were each associated with reduced overall survival. In Cox regression models, interleukin-6 carried a hazard ratio of 1.49, with a 95 percent confidence interval of 1.10 to 2.03 and a p-value of 0.01, while interleukin-8 carried a hazard ratio of 1.83, with a 95 percent confidence interval of 1.01 to 3.31 and a p-value of 0.045. In other words, patients with higher concentrations of these proteins at baseline faced a greater risk of death during follow-up.

The analyses were designed to probe different aspects of the disease. Wilcoxon rank-sum tests assessed associations between cytokine levels and clinical features, Kruskal-Wallis tests evaluated cytokine concentrations in relation to treatment response at three and twelve months, and Cox regression evaluated the prognostic contribution of the cytokines. The researchers considered p-values of 0.05 or lower statistically significant.

The authors conclude that cytokine profiles contribute to the development and progression of HIV-associated Kaposi sarcoma, and that high proinflammatory cytokines are associated with poor treatment response and survival. They suggest that targeting these cytokines and their pathways could inform the development of novel, personalised, Kaposi sarcoma-specific treatment strategies aimed at improving outcomes. Because the study measured baseline cytokines in a trial population of 73 participants with mainly advanced disease, the associations reported here will need further evaluation before they can guide routine clinical decisions, but they add to the evidence that immune signalling molecules carry prognostic information in this cancer.

Subject of Research: Cytokine biomarkers for predicting treatment response and survival in HIV-associated Kaposi sarcoma

Article Title: Cytokine profiles predict response and survival in treatment-naïve individuals with HIV-associated Kaposi sarcoma

Article References: Shaik, F., Uldrick, T. S., Mazinu, M., Gwebushe, N., & Mosam, A. (2026). Cytokine profiles predict response and survival in treatment-naïve individuals with HIV-associated Kaposi sarcoma. AIDS Research and Therapy. https://doi.org/10.1186/s12981-026-00960-8

Image Credits: AI Generated

DOI: 10.1186/s12981-026-00960-8

Keywords: HIV, Kaposi sarcoma, cytokines, biomarkers, interleukin-6, interleukin-8, eotaxin, MIP-1β, overall survival, treatment response, antiretroviral therapy, sub-Saharan Africa