13th Conference on Retroviruses and Opportunistic Infections Denver, Colorado - February 5-8, 2006

Conf Retrovir Opportunistic Infect 2006 Feb 5-8;13:abstract no. 41

Jason Baker , M Larson, A Khoruts, A Haase, and T Schacker
Univ of Minnesota, Minneapolis, US

BACKGROUND: Depletion of memory CD4⁺ T cells within the lamina propria of gut-associated lymphatic tissue (GALT) occurs early in HIV infection. However, the extent to which CD4⁺ T cells return with HAART is unknown.

METHODS: We studied 29 HIV⁺ persons naïve to therapy and 11 HIV­ persons, who underwent a blood draw for peripheral blood mononuclear cells (PBMC) and colonoscopy to obtain ileal tissue. Repeat samples were obtained after initiation of HAART in subjects at 6 months (n = 10). Ileal biopsies were fixed in paraffin and stained for CD4. The absolute fraction of lamina propria tissue area occupied by CD4⁺ cells (“lamina propria CD4 area”) was determined by quantitative image analysis. Absolute and percent CD4⁺ T cells were determined from PBMC at each time point.

RESULTS: The mean lamina propria CD4 area for HIV⁺ and HIV­ persons at baseline was 1.2% (CI = 1.0 to 1.4) and 2.9% (CI = 2.3 to 3.5), respectively, a 59% reduction in the effector memory population of GALT (p = 0.00001). Lamina propria CD4 area was also correlated to the PBMC absolute CD4⁺ T cell count at baseline (corr = 0.33, p = 0.04), however there was a stronger correlation with percentage of CD4⁺ T cells (corr = 0.49, p=0.002). After 6 months of HAART the percentage and absolute CD4⁺ T cell count in PBMC increased from 19 (CI = 16 to 23) to 25 (CI = 18 to 32), and 383 (CI = 288 to 479) to 427 (CI = 264 to 591), respectively. There was only a 10% increase in lamina propria CD4 area in GALT (p = 0.0018) with 6 months of HAART, compared with the 32% increase seen in the percentage of CD4⁺ T cells in PBMC.

CONCLUSIONS: The effector memory CD4⁺ T cells in GALT are rapidly depleted, and our data suggest a limited capacity for repletion with HAART. Further work is required to understand the reasons why repletion of the gut is limited compared to the peripheral expansion of the total CD4⁺ T-cell population, and if a longer duration of HAART would result in better recovery of CD4⁺ T cells in secondary lymphatic tissues.

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2006-02-05
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