[22] THE RECTAL MUCOSA IS A SITE OF HIV-1 REPLICATION AND SHEDDING AND CD4+ T-CELL DEPLETION IN MEN WITH CHRONIC HIV-1 INFECTION

1st International AIDS Society Conference on HIV Pathogenesis and Treatment

Buenos Aires, Argentina - July 8-11, 2001

[TITLE:] THE RECTAL MUCOSA IS A SITE OF HIV-1 REPLICATION AND SHEDDING AND CD4⁺ T-CELL DEPLETION IN MEN WITH CHRONIC HIV-1 INFECTION

[AUTHOR(S):] Tabet S, Brodie S, Dondero D, Haggitt R, Huang M, Kelly C, Celum C
University of Washington, Seattle , Washington, USA

IAS Conf HIV Pathog Treat 2001 Jul 8-11;1st: Abstract No. 22

[ABSTRACT:] Background: The GI tract is an early site of HIV/SIV replication and associated with marked CD4⁺ T cell depletion, yet data is limited in chronic HIV infection. Combination antiretrovirals appear to decrease the amount of HIV RNA in rectal secretions, yet HIV DNA remains detectable from about half of patients on potent therapy. Thus, we assessed the location and amount of HIV replication and quantified CD4⁺ and CD8+ T-cell counts in rectal tissues of 10 chronically HIV-1 infected men.

Methods: Rectal biopsies from 10 HIV+ men and 10 HIV- male controls were examined. TaqMan PCR and in situ hybridization PCR were utilized and were repeated for validation of results. Nine HIV+ men were taking combination antiretrovirals, including protease inhibitors in 6. Among HIV+ participants, mean peripheral CD4⁺ T cell count was 350 cells/ml, and mean plasma HIV RNA was 3.31 log₁₀ copies/ml; three men had plasma HIV RNA below the limit of detection

Results: HIV+ men had significantly fewer rectal mucosal CD4⁺ T cells (mean 49 CD4⁺ T cells/ml) compared to HIV- men [(mean 146 CD4⁺ T cells/ml) (P<0.001)]. Two HIV+ men had HIV RNA detected in mononuclear cells in rectal mucosa; one participant with 331,350 copies/ml in rectal mucosa had plasma HIV RNA < 200 copies/ml. All HIV+ men had detectable HIV RNA by PCR-ISH and DNA (38 +/- 11 DNA+ cells/ mm²) localized to cells predominantly within the intercryptal spaces of the lamina propria.

Conclusions: Massive infection of lymphocytes and macrophages, HIV replication, and CD4⁺ T cell depletion occurs in the rectum of chronically HIV-infected men on antiretrovirals, even among men with undetectable plasma HIV RNA, suggesting that rectal lymphoid tissue may be a separate compartment. Future longitudinal studies are needed to characterize the extent of this reservoir and the kinetics of rectal T cell depletion in the context of topical microbicides and potent combination antiretrovirals.

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