Journal
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
Volume 65, Issue 2, Pages 133-141Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/01.qai.0000437172.08127.0b
Keywords
colon biopsy; ART; microbial translocation; inflammation; HIV; CD4 T-cell recovery
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Funding
- American Foundation for AIDS Research [107854-48-RGRL]
- University of California, San Francisco (UCSF)/Gladstone Center for AIDS Research [P30 AI27763]
- Hurlbut-Johnson Fund
- UCSF/GIVI Center for AIDS Research
- NIAID [U19 AI096109, R37 AI040312, K23 CA157929, R24 AI067039, F32 AI091534]
- California HIV/AIDS Research Program [ID09-SF-067]
- UCSF Clinical and Translational Science Institute [RR024131-01]
- US Department of Veterans Affairs [1 IK2 CX000520-01]
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Objective: Persistent systemic inflammation is associated with the inability of some HIV-infected patients to normalize circulating CD4(+) T-cell levels after years of suppressive antiretroviral therapy. In this study, we sought to understand whether such systemic inflammation is also associated with detectable signs of inflammation in biopsies from the rectosigmoid colon. Design: Immunologic and virological parameters were studied in the peripheral blood and in rectosigmoid colon biopsies from individuals with viral suppression for at least 2 years and with peripheral CD4(+) T-cell levels of <350 cells per cubic millimeter (immunologic nonresponders, n = 18) or >500 cells per cubic millimeter (immunologic responders, n = 16). Methods: Peripheral blood and rectosigmoid colon biopsies were analyzed by flow cytometry, enzyme-linked immunosorbent assay, and quantitative polymerase chain reaction. Results: Nonresponders had elevated T-cell activation and inflammatory cytokines in the circulation, but inflammatory gene expression in colon biopsies was not different as compared with responders, and there was little relationship between blood and colon markers of inflammation. Blood inflammatory markers were positively associated with soluble CD14 levels indicative of monocyte activation. Conclusions: These findings demonstrate that, in the context of treated HIV disease, it is easier to detect parameters of inflammation (including blood monocyte activation) in the peripheral blood than in isolated rectosigmoid colon biopsies. Accordingly, interventions to block such inflammation in this population might be most conveniently and accurately assessed in blood.
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