Browsing by Author "Sieg, Scott F"

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    Determinants of protection among HIV‐exposed seronegative persons: an overview.
    (J Infect Dis, 2010-11-01) Lederman, Michael M; Alter, Galit; Daskalakis, Demetre C; Rodriguez, Benigno; Sieg, Scott F; Hardy, Gareth; Cho, Michael; Anthony, Donald; Harding, Clifford; Weinberg, Aaron; Silverman, Robert H; Douek, Daniel C; Margolis, Leonid; Goldstein, David B; Carrington, Mary; Goedert, James J
    Both clinical experience and a growing medical literature indicate that some persons who have been exposed to human immunodeficiency virus (HIV) infection remain uninfected. Although in some instances this may represent good fortune, cohorts of uninfected persons have been reported who are considered at high risk for infection. In these cohorts a variety of characteristics have been proposed as mediating protection, but to date only the 32–base pair deletion in the chemokine (C‐C motif) receptor 5 gene, which results in complete failure of cell surface expression of this coreceptor, has been associated with high‐level protection from HIV infection. With this in mind, there are probably many other factors that may individually or in combination provide some level of protection from acquisition of HIV infection. Because some of these factors are probably incompletely protective or inconsistently active, identifying them with confidence will be difficult. Nonetheless, clarifying the determinants of protection against HIV infection is a high priority that will require careful selection of high‐risk uninfected cohorts, who should undergo targeted studies of plausible mediators and broad screening for unexpected determinants of protection.
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    Shared monocyte subset phenotypes in HIV-1 infection and in uninfected subjects with acute coronary syndrome.
    (Blood, 2012-11-29) Funderburg, Nicholas T; Zidar, David A; Shive, Carey; Lioi, Anthony; Mudd, Joseph; Musselwhite, Laura W; Simon, Daniel I; Costa, Marco A; Rodriguez, Benigno; Sieg, Scott F; Lederman, Michael M
    The mechanisms responsible for increased cardiovascular risk associated with HIV-1 infection are incompletely defined. Using flow cytometry, in the present study, we examined activation phenotypes of monocyte subpopulations in patients with HIV-1 infection or acute coronary syndrome to find common cellular profiles. Nonclassic (CD14(+)CD16(++)) and intermediate (CD14(++)CD16(+)) monocytes are proportionally increased and express high levels of tissue factor and CD62P in HIV-1 infection. These proportions are related to viremia, T-cell activation, and plasma levels of IL-6. In vitro exposure of whole blood samples from uninfected control donors to lipopolysaccharide increased surface tissue factor expression on all monocyte subsets, but exposure to HIV-1 resulted in activation only of nonclassic monocytes. Remarkably, the profile of monocyte activation in uncontrolled HIV-1 disease mirrors that of acute coronary syndrome in uninfected persons. Therefore, drivers of immune activation and inflammation in HIV-1 disease may alter monocyte subpopulations and activation phenotype, contributing to a pro-atherothrombotic state that may drive cardiovascular risk in HIV-1 infection.