A Low Level of CD4⁺CD28⁺T Cells Is an Independent Predictor of High Mortality in Human Immunodeficiency Virus Type 1–Infected Patients

Abstract

This study investigated coexpression of CD28, CD45RA, and CD45RO on CD4(+) and CD8(+) cells in 107 human immunodeficiency virus (HIV) type 1-infected patients, who were followed-up prospectively and were not treated with highly active antiretroviral therapy, and 65 control subjects. The most important novel finding was that a 50% reduction in CD4(+)CD28(+) cells predicted increased mortality (relative hazards [HR], 1.6; 95% confidence interval [CI], 1.0-2.6; P=.04), even after adjusting for the CD4(+) cell counts, virus load, beta(2)-microglobulin and hemoglobin levels, and HIV disease stage. Patients with progressed HIV infection had decreased concentrations of all studied cell subsets. Concerning the proportions of cells, only CD4(+)CD28(+), CD4(+)CD45RA(+), and CD8(+)CD45RO(+) cells decreased with HIV progression. Low proportions of CD4(+)CD45RA(+), CD8(+)CD45RA(+), and CD8(+)CD45RO(+) cells predicted mortality only in univariate but not in multivariate Cox analyses. If our results are confirmed in other studies, coexpression of CD28 on CD4(+) cells may be a useful marker to evaluate HIV progression.

Differences in HIV-Related Hospitalization Among White, Black, and Hispanic Men and Women of Florida

“…Further, the data did not contain important clinical indicators, such as CD4 T lymphocyte cell level. CD4 T cell count is not only necessary for initiation of antiretroviral therapy in HIV patients, but also is an independent predictor of disease progression and death in HIV infected patients (Hogg, Yip, Chan, et al, 2001;Ostrowski, Gerstoft, Pedersen, et al, 2003). Thus, the findings relating to the correlates of HIV-related death could have been substantially affected if CD4 cell levels were available in our study.…”

HIV Coinfection Impairs CD28‐Mediated Costimulation of Hepatitis C Virus–Specific CD8 Cells

“…Although this phenotype has been attributed to chronic viral antigen stimulation [25], the precise determinants and consequences of this defect are not understood. Lack of CD28 expression on CD4 and CD8 cells appears to be associated with HIV disease progression [30][31][32]. Moreover, CD8 cells that express CD28 appear to be important for an effective immune response to HIV infection [33,34], and the presence of T cells that express CD28 predict a better immune response to neoantigen in HIVinfected patients [35].…”

CD8+ T-Cells: Function and Response to HIV Infection

“…In patients treated with highly active anti-retroviral therapy (HAART) during primary infection, strong CTL and CD4+ T-cell responses were maintained during the first year of therapy [7,193] as opposed to those individuals who were chronically infected [199]. Recently, Ostrowski et al showed the correlation between low levels of CD4+CD28+ T-cells and mortality in HIV-infected patients [191]. Within the CD4+CD28+ subset, they illustrated a decrease in CD4+CD45RA+ and CD8+CD45RO+ cells with viral pathogenesis, indicating improper maintenance and maturation of these cells.…”