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Session 59 Poster Abstracts
Pathogenesis of Primary HIV Infection
Thursday, 1:30 - 3:30 pm
Hall D


285
Gastrointestinal CD4+ T Cells Harbor a Higher Viral Burden than Peripheral Blood CD4+ T Cells in Primary HIV-1 Infection
Saurabh Mehandru*1, M Poles2,5, D Boden3, A Horowitz2,5, K Tenner-Racz4, A Shet1, A Hurley1, P Racz4, and M Markowitz1
1Aaron Diamond AIDS Res Ctr, Rockefeller Univ, New York, NY, USA; 2New York Univ Sch of Med, NY, USA; 3Aaron Diamond AIDS Res Ctr, Rockefeller Univ, New York, NY, USA; 4Berhard Nocht Inst for Trop Med, Hamburg, Germany; and 5Aaron Diamond AIDS Res Ctr, Rockefeller Univ, New York, NY, USA

Background: We have observed a preferential depletion of CD4+ T cells from the gastrointestinal (GI) tract in acute and early HIV-1 infection. Here we compare the markers of immune activation, proliferation, and viral burden of GI CD4+ T cells with peripheral blood (PB) CD4+ T cells at this stage of infection.

Methods:  Subjects with acute and early HIV-1 infection (n = 10) as defined by the presence of plasma viremia and negative or evolving HIV-1 serology underwent phlebotomy and flexible sigmoidoscopy with biopsies. Uninfected subjects (n = 10) served as controls. Flow cytometry was utilized to phenotype GI and PB CD4+ lymphocytes. Immunohistochemistry was performed using the alkaline phosphatase-anti-alkaline phosphatase and peroxidase methods to assess proliferation of GI CD4+ T cells. PCR for HIV-1 proviral DNA and viral RNA was performed on sorted CD4+ T cells from the GI tract and PB.

Results:  Estimated duration of infection ranged from 2 to 14 weeks prior to enrollment. The mean CD4+ T-cell count in the blood was 531 cells/mm3 (380 to 1321) and the mean plasma HIV-1 RNA was 6.3 log10 copies/mL (3.8 to 7.1). A mean of 8.5 GI CD4+ T cells from HIV-infected subjects expressed proliferation marker Ki-67 per unit area as opposed to a mean of 3.8 CD4+ T cells per unit area in HIV-uninfected subjects (p = 0.03). In 2 subjects tested thus far, GI CD4+ T cells had 30- and 80-fold more HIV-1 RNA than PB CD4+ T cells.

  

 

GI CD4+ T cells

PB CD4+ T cells

p value

CD45 RO+ (mean%)

86.8%

62.9%

0.01

HLA DR+ (mean%)

32.7%

13%

<0.01

HLA DR+/CD45RO+(mean%)

30.2%

11.9%

<0.01

HIV-1 DNA (copies per 1000 cells)

93.5

25.4

0.05

Keywords: Primary HIV-1; Gastrointestinal tract; CD4+ T cells