Differences in HIV burden and immune activation within the gut of HIV-positive patients receiving suppressive antiretroviral therapy

Steven A. Yukl, Sara Gianella, Elizabeth Sinclair, Lorrie Epling, Qingsheng Li, Lijie Duan, Alex L M Choi, Valerie Girling, Terence Ho, Peilin Li, Katsuya Fujimoto, Harry Lampiris, C. Bradley Hare, Mark Pandori, Ashley T. Haase, Huldrych F. Günthard, Marek Fischer, Amandeep K. Shergill, Kenneth McQuaid, Diane V. Havlir & 1 others Joseph K. Wong

Research output: Contribution to journalArticle

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Abstract

Background. The gut is a major reservoir for human immunodeficiency virus (HIV) in patients receiving antiretroviral therapy (ART). We hypothesized that distinct immune environments within the gut may support varying levels of HIV. Methods. In 8 HIV-1-positive adults who were receiving ART and had CD4 + T cell counts of >200 cells/μL and plasma viral loads of <40 copies/mL, levels of HIV and T cell activation were measured in blood samples and endoscopic biopsy specimens from the duodenum, ileum, ascending colon, and rectum. Results. HIV DNA and RNA levels per CD4 + T cell were higher in all 4 gut sites compared with those in the blood. HIV DNA levels increased from the duodenum to the rectum, whereas the median HIV RNA level peaked in the ileum. HIV DNA levels correlated positively with T cell activation markers in peripheral blood mononuclear cells (PBMCs) but negatively with T cell activation markers in the gut. Multiply spliced RNA was infrequently detected in gut, and ratios of unspliced RNA to DNA were lower in the colon and rectum than in PBMCs, which reflects paradoxically low HIV transcription, given the higher level of T cell activation in the gut. Conclusions. HIV DNA and RNA are both concentrated in the gut, but the inverse relationship between HIV DNA levels and T cell activation in the gut and the paradoxically low levels of HIV expression in the large bowel suggest that different processes drive HIV persistence in the blood and gut. Trial registration. ClinicalTrials.gov identifier: NCT00884793 (PLUS1).

Original languageEnglish (US)
Pages (from-to)1553-1561
Number of pages9
JournalJournal of Infectious Diseases
Volume202
Issue number10
DOIs
StatePublished - Nov 15 2010

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HIV
T-Lymphocytes
RNA
DNA
Therapeutics
Rectum
Ileum
Duodenum
Blood Cells
Ascending Colon
CD4 Lymphocyte Count
Plasma Cells
Viral Load
HIV-1
Colon
Biopsy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Differences in HIV burden and immune activation within the gut of HIV-positive patients receiving suppressive antiretroviral therapy. / Yukl, Steven A.; Gianella, Sara; Sinclair, Elizabeth; Epling, Lorrie; Li, Qingsheng; Duan, Lijie; Choi, Alex L M; Girling, Valerie; Ho, Terence; Li, Peilin; Fujimoto, Katsuya; Lampiris, Harry; Hare, C. Bradley; Pandori, Mark; Haase, Ashley T.; Günthard, Huldrych F.; Fischer, Marek; Shergill, Amandeep K.; McQuaid, Kenneth; Havlir, Diane V.; Wong, Joseph K.

In: Journal of Infectious Diseases, Vol. 202, No. 10, 15.11.2010, p. 1553-1561.

Research output: Contribution to journalArticle

Yukl, SA, Gianella, S, Sinclair, E, Epling, L, Li, Q, Duan, L, Choi, ALM, Girling, V, Ho, T, Li, P, Fujimoto, K, Lampiris, H, Hare, CB, Pandori, M, Haase, AT, Günthard, HF, Fischer, M, Shergill, AK, McQuaid, K, Havlir, DV & Wong, JK 2010, 'Differences in HIV burden and immune activation within the gut of HIV-positive patients receiving suppressive antiretroviral therapy', Journal of Infectious Diseases, vol. 202, no. 10, pp. 1553-1561. https://doi.org/10.1086/656722
Yukl, Steven A. ; Gianella, Sara ; Sinclair, Elizabeth ; Epling, Lorrie ; Li, Qingsheng ; Duan, Lijie ; Choi, Alex L M ; Girling, Valerie ; Ho, Terence ; Li, Peilin ; Fujimoto, Katsuya ; Lampiris, Harry ; Hare, C. Bradley ; Pandori, Mark ; Haase, Ashley T. ; Günthard, Huldrych F. ; Fischer, Marek ; Shergill, Amandeep K. ; McQuaid, Kenneth ; Havlir, Diane V. ; Wong, Joseph K. / Differences in HIV burden and immune activation within the gut of HIV-positive patients receiving suppressive antiretroviral therapy. In: Journal of Infectious Diseases. 2010 ; Vol. 202, No. 10. pp. 1553-1561.
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abstract = "Background. The gut is a major reservoir for human immunodeficiency virus (HIV) in patients receiving antiretroviral therapy (ART). We hypothesized that distinct immune environments within the gut may support varying levels of HIV. Methods. In 8 HIV-1-positive adults who were receiving ART and had CD4 + T cell counts of >200 cells/μL and plasma viral loads of <40 copies/mL, levels of HIV and T cell activation were measured in blood samples and endoscopic biopsy specimens from the duodenum, ileum, ascending colon, and rectum. Results. HIV DNA and RNA levels per CD4 + T cell were higher in all 4 gut sites compared with those in the blood. HIV DNA levels increased from the duodenum to the rectum, whereas the median HIV RNA level peaked in the ileum. HIV DNA levels correlated positively with T cell activation markers in peripheral blood mononuclear cells (PBMCs) but negatively with T cell activation markers in the gut. Multiply spliced RNA was infrequently detected in gut, and ratios of unspliced RNA to DNA were lower in the colon and rectum than in PBMCs, which reflects paradoxically low HIV transcription, given the higher level of T cell activation in the gut. Conclusions. HIV DNA and RNA are both concentrated in the gut, but the inverse relationship between HIV DNA levels and T cell activation in the gut and the paradoxically low levels of HIV expression in the large bowel suggest that different processes drive HIV persistence in the blood and gut. Trial registration. ClinicalTrials.gov identifier: NCT00884793 (PLUS1).",
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T1 - Differences in HIV burden and immune activation within the gut of HIV-positive patients receiving suppressive antiretroviral therapy

AU - Yukl, Steven A.

AU - Gianella, Sara

AU - Sinclair, Elizabeth

AU - Epling, Lorrie

AU - Li, Qingsheng

AU - Duan, Lijie

AU - Choi, Alex L M

AU - Girling, Valerie

AU - Ho, Terence

AU - Li, Peilin

AU - Fujimoto, Katsuya

AU - Lampiris, Harry

AU - Hare, C. Bradley

AU - Pandori, Mark

AU - Haase, Ashley T.

AU - Günthard, Huldrych F.

AU - Fischer, Marek

AU - Shergill, Amandeep K.

AU - McQuaid, Kenneth

AU - Havlir, Diane V.

AU - Wong, Joseph K.

PY - 2010/11/15

Y1 - 2010/11/15

N2 - Background. The gut is a major reservoir for human immunodeficiency virus (HIV) in patients receiving antiretroviral therapy (ART). We hypothesized that distinct immune environments within the gut may support varying levels of HIV. Methods. In 8 HIV-1-positive adults who were receiving ART and had CD4 + T cell counts of >200 cells/μL and plasma viral loads of <40 copies/mL, levels of HIV and T cell activation were measured in blood samples and endoscopic biopsy specimens from the duodenum, ileum, ascending colon, and rectum. Results. HIV DNA and RNA levels per CD4 + T cell were higher in all 4 gut sites compared with those in the blood. HIV DNA levels increased from the duodenum to the rectum, whereas the median HIV RNA level peaked in the ileum. HIV DNA levels correlated positively with T cell activation markers in peripheral blood mononuclear cells (PBMCs) but negatively with T cell activation markers in the gut. Multiply spliced RNA was infrequently detected in gut, and ratios of unspliced RNA to DNA were lower in the colon and rectum than in PBMCs, which reflects paradoxically low HIV transcription, given the higher level of T cell activation in the gut. Conclusions. HIV DNA and RNA are both concentrated in the gut, but the inverse relationship between HIV DNA levels and T cell activation in the gut and the paradoxically low levels of HIV expression in the large bowel suggest that different processes drive HIV persistence in the blood and gut. Trial registration. ClinicalTrials.gov identifier: NCT00884793 (PLUS1).

AB - Background. The gut is a major reservoir for human immunodeficiency virus (HIV) in patients receiving antiretroviral therapy (ART). We hypothesized that distinct immune environments within the gut may support varying levels of HIV. Methods. In 8 HIV-1-positive adults who were receiving ART and had CD4 + T cell counts of >200 cells/μL and plasma viral loads of <40 copies/mL, levels of HIV and T cell activation were measured in blood samples and endoscopic biopsy specimens from the duodenum, ileum, ascending colon, and rectum. Results. HIV DNA and RNA levels per CD4 + T cell were higher in all 4 gut sites compared with those in the blood. HIV DNA levels increased from the duodenum to the rectum, whereas the median HIV RNA level peaked in the ileum. HIV DNA levels correlated positively with T cell activation markers in peripheral blood mononuclear cells (PBMCs) but negatively with T cell activation markers in the gut. Multiply spliced RNA was infrequently detected in gut, and ratios of unspliced RNA to DNA were lower in the colon and rectum than in PBMCs, which reflects paradoxically low HIV transcription, given the higher level of T cell activation in the gut. Conclusions. HIV DNA and RNA are both concentrated in the gut, but the inverse relationship between HIV DNA levels and T cell activation in the gut and the paradoxically low levels of HIV expression in the large bowel suggest that different processes drive HIV persistence in the blood and gut. Trial registration. ClinicalTrials.gov identifier: NCT00884793 (PLUS1).

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DO - 10.1086/656722

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