Persistence of HIV in gut-associated lymphoid tissue despite long-term antiretroviral therapy.
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.
Chun
Tae-Wook
TW
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. twchun@nih.gov
Nickle
David C
DC
Justement
Jesse S
JS
Meyers
Jennifer H
JH
Roby
Gregg
G
Hallahan
Claire W
CW
Kottilil
Shyam
S
Moir
Susan
S
Mican
Joann M
JM
Mullins
James I
JI
Ward
Douglas J
DJ
Kovacs
Joseph A
JA
Mannon
Peter J
PJ
Fauci
Anthony S
AS
D000998:Antiviral Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D015331:Cohort Studies; D005753:Gastric Mucosa / Q000166:cytology / Q000276:immunology / Q000821:virology*; D015752:Genes, env / Q000235:genetics; D006678:HIV / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D008198:Lymph Nodes / Q000166:cytology / Q000821:virology*; D010802:Phylogeny; D019562:Viral Load; D014766:Viremia / Q000503:physiopathology
D000998:Antiviral Agents