title: The distribution of HIV DNA and RNA in cell subsets differs in gut and blood of HIV-positive patients on ART: implications for viral persistence.
abstract: Even with optimal antiretroviral therapy, human immunodeficiency virus (HIV) persists in plasma, blood cells, and tissues. To develop new therapies, it is essential to know what cell types harbor residual HIV. We measured levels of HIV DNA, RNA, and RNA/DNA ratios in sorted subsets of CD4+ T cells (CCR7+, transitional memory, and effector memory) and non-CD4+ T leukocytes from blood, ileum, and rectum of 8 ART-suppressed HIV-positive subjects. Levels of HIV DNA/million cells in CCR7+ and effector memory cells were higher in the ileum than blood. When normalized by cell frequencies, most HIV DNA and RNA in the blood were found in CCR7+ cells, whereas in both gut sites, most HIV DNA and RNA were found in effector memory cells. HIV DNA and RNA were observed in non-CD4+ T leukocytes at low levels, particularly in gut tissues. Compared to the blood, the ileum had higher levels of HIV DNA and RNA in both CD4+ T cells and non-CD4+ T leukocytes, whereas the rectum had higher HIV DNA levels in both cell types but lower RNA levels in CD4+ T cells. Future studies should determine whether different mechanisms allow HIV to persist in these distinct reservoirs, and the degree to which different therapies can affect each reservoir.
authors.affiliation: Department of Medicine, San Francisco VA Medical Center and University of California, San Francisco.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Yukl
authors.forename: Amandeep K
authors.initials: AK
authors.lastname: Shergill
authors.forename: Terence
authors.initials: T
authors.lastname: Ho
authors.forename: Maudi
authors.initials: M
authors.lastname: Killian
authors.forename: Valerie
authors.initials: V
authors.lastname: Girling
authors.forename: Lorrie
authors.initials: L
authors.lastname: Epling
authors.forename: Peilin
authors.initials: P
authors.lastname: Li
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Wong
authors.forename: Pierre
authors.initials: P
authors.lastname: Crouch
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
authors.forename: Diane V
authors.initials: DV
authors.lastname: Havlir
authors.forename: Kenneth
authors.initials: K
authors.lastname: McQuaid
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sinclair
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Wong
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D004279:DNA, Viral / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D005434:Flow Cytometry; D006678:HIV / Q000235:genetics* / Q000302:isolation & purification; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000821:virology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology; D016131:Lymphocyte Subsets / Q000821:virology*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D018709:Statistics, Nonparametric; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D004279:DNA, Viral; D012367:RNA, Viral
keywords: ART; CD4+ T cell; HIV; HIV-1; gut; ileum; intestine; persistence; rectum; reservoir