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).
Bibliographical noteFunding Information:
Financial support: US Department of Veterans Affairs (Merit Award to J.K.W. and S.Y.); National Institutes of Health (grant P30-AI027763 to S.Y., grant NS051145 to J.K.W. and S.Y., and grant T32 AI60530 to D.V.H. and S.Y.); Swiss National Science Foundation (grant to S.G., grant 324730-130865 to H.F.G., and grant 3100A0-112670 to M.F.).