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Immune Senescence, Activation, and Abnormal T Cell Homeostasis despite Effective HAART, a Hallmark of Early Aging in HIV Disease: "HIV-infected subjects (median 56 years) with good immune reconstitution and viral suppression had immune changes comparable to older (median 88 years) HIV-negative subjects"
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Reported by Jules Levin
CROI 2009 Feb 8-12 Montreal
Seema Desai*1, R Ronquillo1, X Usuga1, J Martinson1, O Adeyemi1,2, A Tenorio1, and A Landay1
1Rush Univ Med Ctr, Chicago, IL, US and 2Stroger Hosp of Cook County and Rush Med Coll, Chicago, IL, US
Background: The introduction of HAART has improved HIV survival, such that many individuals who contracted HIV infection early in the epidemic are now living to an older age. Several immunological alterations that characterize HIV-1 infection are similar to those associated with normal aging. We tested the hypothesis that HIV drives immune activation, turnover, and senescence that leads to accelerated aging in HIV-1 infection.
Methods: We evaluated 10 HIV-1-infected, HAART-suppressed individuals (median age 56 years, viral loads <50 copies/mL, CD4 counts, median 724 cells/mm3); 10 older HIV-negative subjects (median age 88 years), and 5 HIV-negative, young controls (median age 27 years) for markers of immune senescence (CD57+CD28-), immune activation (CD38+HLA-DR+) and regulatory T cells (CD4+CD25hiCD127lo). We evaluated naïve, memory, and effector T cell subsets based on expression of CD45RA CCR7. Student's t test and 1-way ANOVA for comparison within groups was used for statistical analysis.
Results:
In HIV-infected and older HIV-negative subjects, significantly higher (p <0.001) frequency of senescent CD8+ T cells (CD57+CD28-) were found compared to HIV-negative young controls.
Immune activation (CD38+HLA-DR+) was significantly higher in CD8 T cells compared to CD4+ T cells in HIV-infected subjects (p <0.002).
The degree of CD8+ T cell activation was higher in HIV-infected compared to older HIV-negative subjects and HIV-negative young controls (p <0.01).
Regulatory T cell frequencies were equivalent in the HIV-infected and older HIV-negative group and were higher than HIV-negative young controls.
Naïve CD4+ and CD8+ T cells were significantly reduced in HIV-infected and older HIV-negative subjects compared to HIV-negative young controls with proportional increase in terminally differentiated effector T cells. CD4+ and CD8+ central memory T cells were significantly reduced in HIV-infected subjects compared to older HIV-negative subjects (p <0.001 in both subsets).
Conclusions: HIV-infected subjects (median 56 years) with good immune reconstitution and viral suppression had immune changes comparable to older (median 88 years) HIV-negative subjects. Age-dependant changes in HIV-infected compared to young HIV-negative controls are more pronounced in CD8+ T cells, which exhibit higher immune activation and senescence levels and reduced naïve and central memory subsets. These findings have implications on the competency of adaptive immune system and its ability to combat infection.
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