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1 March 2008

Volume 197, Number 5
The Journal of Infectious Diseases 2008;197:714–720
0022-1899/2008/19705-0016$15.00
DOI: 10.1086/527324
MAJOR ARTICLE

Persistence of HIV in Gut-Associated Lymphoid Tissue despite Long-Term Antiretroviral Therapy

Tae-Wook Chun,1,a

David C. Nickle,6,a

Jesse S. Justement,1

Jennifer H. Meyers,1

Gregg Roby,1

Claire W. Hallahan,2

Shyam Kottilil,1

Susan Moir,1

JoAnn M. Mican,4

James I. Mullins,6

Douglas J. Ward,7

Joseph A. Kovacs,5

Peter J. Mannon,3 and

Anthony S. Fauci1

1Laboratory of Immunoregulation, 2Biostatistical Research Branch, 3Laboratory of Host Defense, 4Division of Clinical Research, National Institute of Allergy and Infectious Diseases, 5Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland; 6Department of Microbiology, University of Washington, Seattle; 7Dupont Circle Physicians Group, Washington, DC

Human immunodeficiency virus (HIV) persists in peripheral blood mononuclear cells despite sustained, undetectable plasma viremia resulting from long-term antiretroviral therapy. However, the source of persistent HIV in such infected individuals remains unclear. Given recent data suggesting high levels of viral replication and profound depletion of CD4+ T cells in gut-associated lymphoid tissue (GALT) of animals infected with simian immunodeficiency virus and HIV-infected humans, we sought to determine the level of CD4+ T cell depletion as well as the degree and extent of HIV persistence in the GALT of infected individuals who had been receiving effective antiviral therapy for prolonged periods of time. We demonstrate incomplete recoveries of CD4+ T cells in the GALT of aviremic, HIV-infected individuals who had received up to 9.9 years of effective antiretroviral therapy. In addition, we demonstrate higher frequencies of HIV infection in GALT, compared with PBMCs, in these aviremic individuals and provide evidence for cross-infection between these 2 cellular compartments. Together, these data provide a possible mechanism for the maintenance of viral reservoirs revolving around the GALT of HIV-infected individuals despite long-term viral suppression and suggest that the GALT may play a major role in the persistence of HIV in such individuals.

Received 27 June 2007; accepted 6 September 2007; electronically published 8 February 2008.

Reprints or correspondence: Tae-Wook Chun, PhD, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 6A32, 9000 Rockville Pike, Bethesda, Maryland 20892 ().

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Steven Yukl and Joseph K. Wong. (2008) Blood and Guts and HIV: Preferential HIV Persistence in GI Mucosa. The Journal of Infectious Diseases 197:5, 640-642
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  • Potential conflicts of interest: none declared.

    Financial support: National Institutes of Health (grant P30 AI27757 to J.I.M) and the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health.

  • (See the editorial commentary by Yukl and Wong on pages 640–2.)

  • aT-.W.C. and D.C.N. contributed equally to this work.

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