icon-folder.gif   Conference Reports for NATAP  
 
  IDSA Conference
(Infectious Disease Society Association)
San Diego, CA Oct 17-21 2012
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HIV-infected adults with suppressed viremia on antiretroviral therapy have dysfunctional HDL that is associated with T cell activation
 
 
  IDSA Oct 17-21 2012
Reported by Jules Levin
Program Abstract:
Background:

Limited data suggest that residual immune activation in HIV infection has an effect on HDL function. We investigated whether HDL function is associated with T cell activation in HIV-infected subjects.

Methods:

Using a novel assay based on the effect of HDL on the oxidation of dihydrorhodamine (DHR) we determined redox properties of HDL isolated from fresh plasma from 150 HIV-1 infected patients with HIV-1 RNA <500 copies/mL on antiretroviral therapy (ART) and from 50 healthy volunteers. The DHR oxidation rate (DOR) for 1.25 ug of HDL cholesterol from each subject were normalized as ratios to the DOR of a control pool of plasma HDL from 30 healthy control subjects (nDOR), where nDOR >>1 suggests dysfunctional HDL. Immune activation was assessed on CD8 T cells (#CD38, %CD38+HLADR+) of HIV-1 infected patients. Analysis of variance and Spearman r were used to evaluate for associations between nDOR and categorical and continuous variables, respectively. Significant (p<0.05) variables (Table) were considered in multivariate models.

Results:

The characteristics of the HIV infected subjects are shown in Table. The mean nDOR value for the HIV-1-infected group was 1.33 0.21 versus 0.87 0.15% for 50 healthy subjects (p<0.0001). Higher nDOR was associated with increased immune activation markers such as higher frequency of activated T CD8 cells (r=0.40; p<0.0001) and #CD38 on CD8 T cells (r=0.36; p<0.0001). Higher DOR was significantly associated with age, BMI, duration of HIV infection and ART, CD4 nadir, baseline CD4, and lipids (Table). After adjustment for significant covariates in multiple regression analysis, DOR remained significantly associated with markers of immune activation (p=0.002 for CD38 mol in CD8 (+); p<0.001 for % activated CD8 (+) T Cells.

Conclusion:

Our results demonstrate that HIV-1-infected subjects with suppressed viremia on ART have largely dysfunctional HDL that is associated with T cell activation despite successful virologic therapy. Further studies are warranted to evaluate the interplay between dysfunctional HDL and HIV-induced immune activation.

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