Cited by 867HIV Research and TreatmentHIV/AIDS Research and InterventionsHIV-related health complications and treatments

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Severe CD4+T-Cell Depletion in Gut Lymphoid Tissue during Primary Human Immunodeficiency Virus Type 1 Infection and Substantial Delay in Restoration following Highly Active Antiretroviral Therapy

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Guadalupe, Moraima, Reay, Elizabeth, Sankaran, Sumathi, Prindiville, Thomas, Flamm, Jason, McNeil, Andrew, Dandekar, Satya·2003·Journal of Virology

DOI 10.1128/jvi.77.21.11708-11717.2003PMC PMC229357

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Abstract

Gut-associated lymphoid tissue (GALT) harbors the majority of T lymphocytes in the body and is an important target for human immunodeficiency virus type 1 (HIV-1). We analyzed longitudinal jejunal biopsy samples from HIV-1-infected patients, during both primary and chronic stages of HIV-1 infection, prior to and following the initiation of highly active antiretroviral therapy (HAART) to determine the onset of CD4+T-cell depletion and the effect of HAART on the restoration of CD4+T cells in GALT. Severe depletion of intestinal CD4+T cells occurred during primary HIV-1 infection. Our results showed that the restoration of intestinal CD4+T cells following HAART in chronically HIV-1-infected patients was substantially delayed and incomplete. In contrast, initiation of HAART during early stages of infection resulted in near-complete restoration of intestinal CD4+T cells, despite the delay in comparison to peripheral blood CD4+T-cell recovery. DNA microarray analysis of gene expression profiles and flow-cytometric analysis of lymphocyte homing and cell proliferation markers demonstrated that cell trafficking to GALT and not local proliferation contributed to CD4+T-cell restoration. Evaluation of jejunal biopsy samples from long-term HIV-1-infected nonprogressors showed maintenance of normal CD4+T-cell levels in both GALT and peripheral blood. Our results demonstrate that near-complete restoration of mucosal immune system can be achieved by initiating HAART early in HIV-1 infection. Monitoring of the restoration and/or maintenance of CD4+T cells in GALT provides a more accurate assessment of the efficacy of antiviral host immune responses as well as HAART.

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Authors: Guadalupe, M., Reay, E., Sankaran, S., Prindiville, T., Flamm, J., McNeil, A., & Dandekar, S.
Affiliations: University of California, Davis (US)
Departments of Medical Microbiology & Immunology
The Permanente Medical Group Inc.
ORCID: Flamm, Jason
Dandekar, Satya
Venue: Journal of Virology
Publisher: American Society for Microbiology
Published: 2003-11
Volume: 77
Issue: 21
Pages: 11708-11717
ISSN: 0022-538X (ISSN-L)
1098-5514
DOI: 10.1128/jvi.77.21.11708-11717.2003
PMC: PMC229357
OpenAlex: W2076120354
Cited by: 866
References: 24
Citations by year: 2026: 13 · 2025: 7 · 2024: 11 · 2023: 14 · 2022: 23 · 2021: 27 · 2020: 21 · 2019: 26 · 2018: 26 · 2017: 32 · 2016: 42 · 2015: 45 · 2014: 48 · 2013: 62 · 2012: 60
FWCI: 7.86
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Journal of Virology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
National Institute of Diabetes and Digestive and Kidney Diseases (DK 61297, R01DK061297)
Topics: Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
Health Sciences › Medicine › Infectious Diseases › HIV/AIDS Research and Interventions
Health Sciences › Medicine › Infectious Diseases › HIV-related health complications and treatments
Keywords: HIV-1 infection, CD4+ T cell depletion, gut-associated lymphoid tissue, highly active antiretroviral therapy, CD4+ T cell recovery, jejunal biopsy, lymphocyte homing, nonprogressors, gene expression profiling, early treatment initiation
MeSH terms: Adult, Cell Movement, Chronic Disease, Female, Flow Cytometry, Humans, Immunohistochemistry, Jejunum, Lymphocyte Activation, Lymphoid Tissue, Male, Middle Aged, Time Factors, CD4-Positive T-Lymphocytes, HIV-1, HIV Infections, CD8-Positive T-Lymphocytes, CD4 Lymphocyte Count, Antiretroviral Therapy, Highly Active

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Severe CD4+T-Cell Depletion in Gut Lymphoid Tissue during Primary Human Immunodeficiency Virus Type 1 Infection and Substantial Delay in Restoration following Highly Active Antiretroviral Therapy

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