Program Schedule

1609
Plasma markers of immune activation likely reflect related but distinct processes of cellular immune activation in HIV-infected persons before and after suppression of viremia by antiretroviral therapy: ACTG 5260

Session: Poster Abstract Session: HIV: Basic Science
Saturday, October 11, 2014
Room: The Pennsylvania Convention Center: IDExpo Hall BC

 

Background

Cellular markers of immune activation are strong predictors of disease progression and comorbidities in HIV infection. It is unclear whether soluble biomarkers of T cell (sIL-2r) and monocyte (MNC) activation (sCD14, sCD163) represent robust surrogate markers of cellular immune activation during the course of antiretroviral therapy (ART).

Methods :

In the ACTG A5260s study, Spearman correlations between biomarkers of T-cell and MNC activation and proinflammatory MNC (pMNCs) subsets were estimated at entry and 96 weeks in 328 HIV-infected treatment-naive subjects randomized equally to tenofovir/emtricitabine plus raltegravir or ritonavir-boosted atazanavir or darunavir. Analyses were restricted to 234 (71%) subjects who had HIV-1 RNA <50 copies/ml by week 24 and thereafter. Plasma and cellular immune markers were determined by ELISA and flow cytometry, respectively.

Results:

sIL-2r and sCD163 were significantly associated with T cell activation (% CD38+DR+ CD8 T cells) at entry and 96 weeks. sCD163 was also associated with both T cell activation and  pMNCs (% CD14+CD16+ MNCs)  after successful ART. sCD14 was significantly associated with T cell activation and pMNCs only at entry. After 96 weeks of ART, sIL-2r and sCD14 were not associated with cellular markers of pMNCs (Table).

Conclusion:

There were modest associations between all plasma markers of immune activation and cellular markers of T activation in viremic subjects. However, after successful ART, only sCD163 had a modest association with cellular markers of T cell activation. Plasma markers of immune activation may reflect different immune activation pathways with differential dependence on viral replication versus immune dysregulation that is not reversed with viral suppression by ART.

 

 

 

Plasma Markers

 

Week 0

Week 96

Cellular

Markers

sIL-2r

sCD14

sCD163

sIL-2r

sCD14

sCD163

% CD38+DR+ of CD8+ T cells (T cell activation)

0.36 (<0.001)

0.25 (<0.001)

0.38 (<0.001)

0.18 (0.011)

0.11 (0.11)

0.40 (<0.001)

% CD14+CD16+ of MNCs (pMNCs)

0.07 (0.30)

0.27 (<0.001)

0.06 (0.38)

-0.06 (0.40)

0.07 (0.32)

0.16 (0.022)

% CD163+ of MNCs (pMNCs)

-0.01 (0.90)

0.03 (0.65)

-0.02 (0.78)

-0.07 (0.29)

-0.02 (0.81)

-0.05 (0.52)

 

 

1Similar correlations on CD4+; 2associations with CD16 (h) CD14 (l) not apparent.

 

Theodoros Kelesidis, MD, PhD1, Carlee Moser, PhD2, Grace a. Mccomsey, MD3,4, Todd Brown, MD, PhD5, Heather Ribaudo, PhD2, Thuy Tien T Tran2, Otto Yang, MD6, James Stein, MD7 and Judith Currier, MD, MSc8, (1)David Geffen School of Medicine at UCLA, Los Angeles, CA, (2)Harvard School of Public Health, Boston, MA, (3)Case Western Reserve University School of Medicine, Cleveland, OH, (4)University Hospitals Case Medical Center, Cleveland, OH, (5)Johns Hopkins University, Baltimore, MD, (6)David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, (7)University of Wisconsin School of Medicine and Public Health, MADISON, WI, (8)UCLA, Los Angeles, CA

Disclosures:

T. Kelesidis, None

C. Moser, None

G. A. Mccomsey, None

T. Brown, None

H. Ribaudo, None

T. T. T. Tran, None

O. Yang, None

J. Stein, None

J. Currier, None

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