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We reported an atypical cohort of antiretroviral-treated patients who developed or had unremitting Kaposi’s sarcoma (KS) despite having undetectable viral loads and high CD4 cell counts. The KS course of these patients is indolent, resembling elderly or classical HIV- KS. Since HIV infection is associated with accelerated immunologic aging (“immunosenescence”), and since classical HIV- KS of the elderly may be related to age-associated T cell dysfunction, we hypothesized that T cell immunosenescence would be associated with the presence of this atypical KS.
We identified 19 individuals on antiretroviral therapy (ART) who developed or had unremitting KS after an interval of at least 24 months with viral loads <75 copies RNA/mL and peripheral CD4 cell counts >300 cells/mm3. We also recruited 47 HIV+ KS- controls on ART with viral loads <75 copies RNA/mL and peripheral CD4 cell counts >300 cells/mm3. Global immunosenescence markers CD28 and CD57, as well as naïve cell phenotypic coexpression of CD27+/CD28+/CD45RA+, were examined in peripheral blood via flow cytometry.
All cases and controls were men. Cases and controls were not significantly different with regard to CD4 or CD8 cell count and viral load, though age was significantly different (p<0.001, Table Table1).1). Cases had a higher proportion of CD57+CD8+ T cells vs. controls (median of 41.5% vs. 27.7%, age-adjusted p=0.005). There was a trend suggesting that cases had a higher frequency of CD57+CD4+ T cells than controls (median of 7.4% vs. 3.7%, age-adjusted p=0.07). Cases also had a higher proportion of CD28-/CD4+ cells (median of 9.1% vs. 4.8%, age adjusted p=0.030) and CD28-/CD8+ cells (median of 60.5% vs. 51.3%, age adjusted p=0.044) vs. controls. Cases had a lower proportion of CD27+/CD28+/CD45RA+ naive CD8+ T cells vs. controls (median of 11.3% vs. 20.7%, age adjusted p=0.022). There was a trend suggesting that cases had a lower frequency of CD27+/CD28+/CD45RA+ naive CD4+ cells vs. controls (median of 23.0% vs. 32.2%, age adjusted p=0.11).
The indolent KS observed among antiretroviral-treated patients is associated with a higher frequency of immunosenescent T cells, characterized by global immunosenescence markers and decreased numbers of naive cells. These markers provide more evidence that KS in these patients may be a consequence of enduring HIV-associated T cell dysfunction and T cell immunosenescence. This association of immunosenescence in otherwise well-treated HIV infection with an AIDS-defining malignancy may provide important insights into the role of immune dysfunction as a cause of premature morbidity commonly observed in the HIV+ cohorts.
This article has been published as part of Infectious Agents and Cancer Volume 5 Supplement 1, 2010: Proceedings of the 12th International Conference on Malignancies in AIDS and Other Acquired Immunodeficiencies (ICMAOI).The full contents of the supplement are available online at http://www.biomedcentral.com/1750-9378/5?issue=S1.