Abstract
AIDS-related Kaposi’s sarcoma (AIDS-KS) risk remains substantially elevated compared with the general population, even among patients who receive effective combination antiretroviral therapy. This study investigated the role of inflammatory and immune activating biomarkers in AIDS-KS in men who have sex with men in the Multicenter AIDS Cohort study between 1984 and 2010. Concentrations of 24 serum biomarkers; IL-1β, IL-2, IL-6, IL-8, IL-10, IL-12p70, sGP130, sIL-2Rα, sIL-6R, eotaxin, MCP-1, MCP4, MIP 1β, TARC, BLC-BCA1, IP-10, GM-CSF, IFN-γ, BAFF, sCD14, CD27, sTNFR-2, sCRP, and TNF-α were tested longitudinally in 1,501 men. The concentrations of each biomarker were compared between AIDS-KS cases and controls at multiple time points, 0–1 years, 1–2 years, 2–3 year, 3–5 years and over 5 years, prior to KS diagnosis or study termination, using univariate non-parametric Kruskal-Wallis tests and logistic regression, adjusted for HBV and HCV co-infection, race/ethnicity, age at last visit, education, smoking and CD4+ cell count. In univariate analyses, concentrations of four markers were consistently higher in cases; sIL-2Rα, IP-10, sTNFR-2, MCP-1, and five were higher in controls; GM-CSF, IL-6, MIP-1β, sCRP, sGP130. In the adjusted models concentrations of four markers were significantly inversely associated with AIDS-KS risk including sGP130 (OR=0.14, 95% CI = 0.03–0.73, BAFF (OR=0.60, 95% CI =0.16–0.90), sCRP (OR=0.61, 95% CI = 0.43–0.87) and IL-6 (OR=0.51, 95% CI = 0.35–0.76). These results support a role for markers of immune activation and inflammation in AIDS-KS and may highlight pathways to be targeted for risk stratification or therapeutics.
Highlights
AIDS related Kaposi’s sarcoma (AIDS-KS) was one of the first HIV related complications categorized as an AIDS defining illness
The average BMI was 23.76 (SE = 3.66) kg/m2 in AIDS-related Kaposi’s sarcoma (AIDS-KS) cases and controls were slightly overweight with an average of 25.42 (SE = 4.39) kg/m2
Among cases 51.61% took no therapy compared to 11.66% of controls; 22.58% of cases had monotherapy compared to 3.37% of controls; 9.68% of cases took combination therapy compared to 6.90% of controls and only 16.13% of cases took potent ART compared to 78.07% of controls
Summary
AIDS related Kaposi’s sarcoma (AIDS-KS) was one of the first HIV related complications categorized as an AIDS defining illness This cancer was studied extensively at the beginning of the epidemic, as there is an approximate 30% risk of development if coinfected with HIV and the human herpes virus 8 (HHV-8) and untreated over 10 years [1, 2]. After highly active antiretroviral therapy (HAART) was introduced, it was expected the rates of AIDS-KS would decrease back to pre-epidemic levels in the US, approximately 3 cases per 1000 person-years from the height of epidemic at 25 cases per 1000 person-years [2] These rates only subsided to approximately 7.5 cases per 1000 person-years, adding significant morbidity and mortality for those who are HIV positive [2, 3, 4, 5, 6]. HHV-8 is a lifelong infection for which there are currently no treatments available [12]
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