Assessment of Biological and Epidemiological Components of AIDS Associated Kaposi’s Sarcoma in the Multicenter AIDS Cohort Study: An Analysis of Serum Markers of Inflammation and Immune Activation in Cases of AIDS Associated Kaposi’s Sarcoma
- Author(s): Bolanos, Rachel Shoshanna;
- Advisor(s): Detels, Roger;
- et al.
The goal of this research was to examine the demographic, therapeutic and biological factors contributing to AIDS related Kaposi’s sarcoma (AIDS-KS) in men who have sex with men. This collection of three studies focuses on the effect of HIV medication, demographic factors, and inflammatory and immune activating biomarkers prior to diagnosis with AIDS-KS using data collected prospectively in the Multicenter AIDS Cohort Study (MACS) from 1984 to 2009. The MACS includes over 7,000 men over the course of 30 years, which captures the dynamic nature of HIV-related illnesses throughout the epidemic. Subjects in the study participated in bi-annual visits over the course of over 30 years where they contributed data including information on clinical, laboratory and behavioral data. Serum blood samples collected for over 1,800 men were used for an in-depth analysis of inflammatory and immune activating biomarkers using multiplex assays.
The studies were able to use this rich data source to do longitudinal analysis using Cox proportional hazards models to assess the effects of HIV medications and the concentrations of biomarkers preceding AIDS-KS diagnosis. In addition, a nested case control design with logistic and stepwise modeling was conducted to ensure the adequate accounting for all participants. In each of these models, demographic information including smoking, alcohol use, hepatitis B and C infection, race education, age and other relevant covariates were accounted for using the bi-annually collected study information. The results of these studies indicate the benefit of HIV medication use in the context of HIV and human herpes virus 8 (HHV-8) coinfection, with added benefit appearing to come from combinations of these medications. Inflammatory biomarkers also held notable patterns prior to diagnosis with distinct depression of levels of IL-6 and sGP-130 and an increase in IL-10 and sIL-2α indicating increased levels of inflammation and HHV-8 lytic activity. These studies indicate the increased benefit of HIV medication use and increasing levels of viral activity and inflammation prior to AIDS-KS diagnosis, but the potential for temporal difference in therapy administration as well as inconsistent use and uncontrolled confounding should not be ignored.