TREASURE HUNT: HIV DNA IN DISTINCT SUBSETS IN THE BLOOD, TERMINAL ILEUM AND RECTUM
. Augustin M. Mar 4, 2019; 258552; 335 Topic: Other
Mr. Max Augustin
Mr. Max Augustin
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Abstract
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Background
The gut associated lymphatic tissue (GALT) shows major differences in immune cell composition along the intestine. The largest part of the GALT is located in the terminal ileum (TI), and the HIV reservoir has been associated with CXCR3 and PD1 expression on CD4+ T-cells, and the chemokine IP-10. However, in contrast to the rectum (R), studies of the TI are scarce due to the difficulty in obtaining biopsies. The aim of this study was to compare the interplay of IP-10, CXCR3, PD-1 and the size of the viral reservoir between peripheral blood (PB), R and TI in HIV+ patients on ART.

Methods
Paired PB, TI and R samples from 20 HIV+ patients (HIV-RNA < 20 cop/ml) and 11 healthy controls were studied (median CD4+ T cells of HIV+ [cells/μl]: 696 [495-955]; time on ART [years]: 8 [5.5-10]). Expression of CXCR3 and PD-1 on sorted CD4+CD45RO+ T-cells memory subsets (T central memory (TCMCD27+CCR7+), T transitional memory (TTMCD27+CCR7-), and effector memory cells (TEMCD27-CCR7-)) was assessed. Cell associated total HIV DNA was quantified by qPCR within memory subsets (expression as cop/CD4*10^6). IP-10 in serum and tissue supernatant was measured by ultrasensitive digital ELISA (Simoa; Quanterix, pg/mL). Data were analyzed using Mann-Whitney and Spearman rank (correlation) tests.


Results
HIV+ patients had significantly higher HIV-DNA levels in the TI compared to PB and R. Distribution of memory subsets in PB, TI and R was similar between HIV+ and controls. However, in HIV+ in all compartments PD1 and CXCR3 expression was significantly higher. HIV+ had increased expression of CXCR3 and PD-1 on memory subsets in the TI+R as opposed to PB: TI showed highest PD1 expression in TTM, whereas CXCR3 was highly expressed on TCM in R.

Conclusion
Highest levels of HIV-DNA are found in TI. Increased IP-10 levels as well as PD1 and CXCR3 expression in HIV+ TI correlate with total HIV DNA. Different anatomical compartments of the intestinal immune system contribute to maintain the HIV-reservoir.
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