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

• Published in: The Journal of infectious diseases Vol. 208; no. 8; pp. 1212 - 1220
• Main Authors: Yukl, Steven A., Shergill, Amandeep K., Ho, Terence, Killian, Maudi, Girling, Valerie, Epling, Lorrie, Li, Peilin, Wong, Lisa K., Crouch, Pierre, Deeks, Steven G., Havlir, Diane V., McQuaid, Kenneth, Sinclair, Elizabeth, Wong, Joseph K.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 15.10.2013
• Series: Editor's choice
• Subjects: Adult; Anti-Retroviral Agents - therapeutic use; Biological and medical sciences; Blood; Blood cells; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - virology; Cells; DNA; DNA, Viral - analysis; DNA, Viral - blood; DNA, Viral - metabolism; Flow Cytometry; Fundamental and applied biological sciences. Psychology; HIV; HIV - genetics; HIV - isolation & purification; HIV Infections - blood; HIV Infections - drug therapy; HIV Infections - immunology; HIV Infections - virology; HIV/AIDS; Human immunodeficiency virus; Human viral diseases; Humans; Ileum; Infectious diseases; Leukocytes; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - virology; Lymphocyte Subsets - virology; Major and Brief Reports; Male; Medical sciences; Microbiology; Middle Aged; Miscellaneous; Rectum; RNA; RNA, Viral - analysis; RNA, Viral - blood; RNA, Viral - metabolism; Statistics, Nonparametric; T lymphocytes; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Load; Virology; Immunopathology; Digestive system; Gut; Retroviridae; AIDS; Immune deficiency; Lentivirus; Cell subpopulation; Blood; Virus; Infection; Viral disease; Human immunodeficiency virus; HIV-1; ileum; ART; CD4+ T cell; intestine; HIV; gut; persistence; rectum; reservoir
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jit308

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.