thesis

Assessing the Prognostic Significance of CD8+ T-Cell Counts in Determining the Risk of Myocardial Infarction in the Setting of HIV Infection

Abstract

There is a growing body of research to suggest that Human Immunodeficiency Virus (HIV) infection is associated with an increased risk for myocardial infarction (MI) although the underlying processes remain unclear. An assessment of MI risk using a commonly-available measure of the immune status is therefore of Public Health importance. CD8+ and CD4+ T-cell counts are periodically measured in the routine management of HIV-infected patients. However, CD8+ T-cell counts are often not reported or are simply incorporated into the calculation of a CD4+/CD8+ ratio. Total CD8+ T-cell counts have been shown to be associated with an increased risk for MI in at least one recent study. A few other studies have examined this association indirectly by using the CD4+/CD8+ ratio, but only considered MI surrogates (e.g. subclinical coronary atherosclerosis) as an outcome. Also, measuring cell-surface markers of CD8+ T-cell activation and HIV-specific CD8+ T cell counts is costly and often not requested in the routine management of HIV infection. This study investigated the association between total CD8+ T-cell counts and MI risk among a large cohort of HIV-uninfected and HIV-infected Veterans. Using Cox proportional hazard regression models, the results suggest that MI risk is associated with a high CD8+ T-cell count of ≥1066 cells/ mm3 (Adjusted HR = 1.82, P <0.001, 95% CI: 1.46 to 2.28). They also suggest that the risk for MI posed by total CD8+ T-cell counts should be interpreted in the context of CD4+ T-cell clinical cut-points, or the overall immune status. The degree of MI risk in the cohort differed depending on the level of the immunosuppression. Total CD8+ T cell-counts seemed to modestly improve the risk stratification provided by CD4+ T-cell clinical cut-points, though the mechanisms are still unclear. Future studies will be instrumental in understanding the role of the immune system in MI risk prediction

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