Search

Objective: Cardiovascular disease (CVD) contributes significantly to HIV-related morbidity and mortality. Chronic immune activation and inflammation are thought to augment the progression of atherosclerotic disease. In this retrospective, case–control study of HIV-infected individuals, we investigated the association of traditional cardiac risk factors, HIV-related disease, and inflammation with CVD events. Methods: HIV-infected individuals who experienced an incident CVD event while enrolled in National Institutes of Health clinical protocols from 1995 to 2009 were matched 2: 1 to HIV-infected individuals without known CVD. Markers of inflammation and cell activation were measured in serum or plasma using ELISA-based assays and peripheral mononuclear cells by four-color flow cytometry. Results: Fifty-two patients experienced an incident CVD event. Events were related to smoking, dyslipidemia, hyperglycemia, and family history as well as elevated D-dimer, soluble vascular cell adhesion molecule-1, tissue inhibitor of metalloproteinase-1, and soluble tissue factor, but not high-sensitivity C-reactive protein. No significant differences in antiviral therapy, CD4+ T-cell count, or CD38 and human leukocyte antigen-DR expression were identified between patients and controls. In multivariable analysis, smoking, family history, D-dimer, and glucose were independently related to CVD risk. Conclusion: In this cohort, CVD risk was related to traditional CVD risk factors and markers of thrombosis and endothelial damage, but not to high-sensitivity C-reactive protein or markers of T-cell activation such as CD38/human leukocyte antigen-DR coexpression. D-dimer may help identify HIV-infected patients at elevated CVD risk.

Objective—To determine the effects of interleukin (IL)-2 treatment on inflammatory and thrombotic biomarkers in chronically HIV-infected adults receiving antiretroviral therapy (ART). Methods—Cryopreserved plasma was evaluated retrospectively for CRP and D-dimer at baseline, end of an IL-2 cycle, and long-term follow-up from 2 randomized, controlled trials: 1) 57 IL-2-naive adults receiving either 3–6 cycles of IL-2 plus ART (nucleoside analogues) or ART alone for 12 months; 2) 40 IL-2-experienced adults on HAART who either interrupted or continued therapy for

Background: Intermittent administration of interleukin (IL)-2 to HIV infected patients leads to CD4 T-cell expansions that are associated with decreased CD4 T-cell turnover. IL-2 is under evaluation in antiretroviral therapy (ART) interruption studies, but it is unclear how the emergence of viremia may affect CD4 expansions. Methods: CD4 T-cell responses were evaluated in 27 HIV infected patients on long-term intermittent IL-2 therapy who underwent ART interruption immediately after an IL-2 cycle (‘IL-2/off’) and compared with responses from a previous IL-2 cycle while on continuous ART (‘IL-2/on’). Immunophenotypic analysis, including intracellular Ki67 staining, of cryopreserved peripheral blood mononuclear cells was performed. Results: CD4 T-cell increases, in naive and central memory CD4 T-cell subsets, were observed in the IL-2/on (106 and 327 cells/μl, respectively) and IL-2/off (84 and 184 cells/μl, respectively) cycles 1 month following IL-2 administration. These increases were greater during the IL-2/on cycle (P = 0.05, P = 0.01, respectively). In both cycles, the change in CD4 T-cell count correlated with the change in CD4/CD25 T cells. In the IL-2/off cycle, the change in the proportion of CD4 T cells expressing Ki67 was associated with both the changes in viral load (r = 0.64, P = 0.001) and the changes in CD4 T cells (r = −0.56, P = 0.01). Conclusions: IL-2 administration followed by ART interruption led to significant, although blunted, CD4 T-cell increases. IL-2 induced CD4 T-cell increases in the setting of emergent viremia were associated with decreased CD4 T-cell activation that counteracted the viremia-induced increases in CD4 T-cell activation.