Abstract
HIV-associated/epidemic Kaposi’s sarcoma (EpKS) is an AIDS-defining angio-proliferative malignancy. It can be treated with antiretroviral therapy (ART) alone or with ART plus cytotoxic chemotherapy. ART-treated EpKS can either respond or worsen upon treatment. This study aimed at identifying immunological markers of ART-treatment response. We compared responders (those with clinical EpKS tumor regression) versus poor responders (those with progressive or non-responsive EpKS). We measured plasma cytokine and chemokine levels using cytometric bead assays. Kaposi’s sarcoma herpesvirus (KSHV) neutralizing antibody (nAb) responses were also quantified to test associations with treatment outcome. Interleukin (IL)-5 levels were significantly elevated in responders versus poor-responders at baseline (0.76pg/ml vs. 0.37pg/ml; p<0.01) and follow-up (0.56pg/ml vs. 0.37pg/ml; p<0.01); IL-6 was lower in responders than poor-responders at follow-up (600fg/ml vs. 4272fg/ml; p<0.05). IP-10/CxCL-10 was significantly lower at follow-up in responders versus poor-responders (187pg/ml vs. 528pg/ml; p<0.01). KSHV nAb were not significantly differential between responders and poor-responders. In conclusion, high plasma IL-5 at baseline could be a marker for ART-treated KS tumor regression, whereas increased pro-inflammatory cytokine IL-6, and the chemokine IP-10, associate with KS tumor progression.
Highlights
Kaposi’s sarcoma (KS) is a vascular malignancy highly prevalent in sub-Saharan Africa (SSA) [1,2,3]
This study was conducted on adult KS patients presenting at the University Teaching Hospital (UTH) in Lusaka, Zambia
We successfully recruited 27 eligible study participants. 5 of the recruited participants were lost to follow up after the baseline assessment, 1 participant was commenced on cytotoxic chemotherapy at another health facility and was no longer eligible for follow up, 13 participants had worsening KS within 6 months of antiretroviral therapy (ART) initiation, and 4 participants had stable disease or regression of KS lesions after at least 6 months of follow up
Summary
Kaposi’s sarcoma (KS) is a vascular malignancy highly prevalent in sub-Saharan Africa (SSA) [1,2,3]. Human herpesvirus type 8 (HHV-8), which is known as Kaposi’s sarcoma-associated herpesvirus (KSHV), has been implicated as the etiological agent of all four types of KS [4]. These are: i) Classic KS—occurs in elderly men of Mediterranean origin; ii) Iatrogenic KS —a result of immunosuppressive therapy; iii) Endemic KS—seen among the HIV-negative population in SSA; and iv) Epidemic or AIDS-associated KS (EpKS)–associated with HIV-.
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