Viral suppression and immune restoration in the gastrointestinal mucosa of human immunodeficiency virus type 1-infected patients initiating therapy during primary or chronic infection

Moraima Guadalupe, Sumathi Sankaran-Walters, Michael D. George, Elizabeth Reay, David Verhoeven, Barbara Shacklett, Jason Flamm, Jacob Wegelin, Thomas P Prindiville, Satya Dandekar

Research output: Contribution to journalArticle

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Abstract

Although the gut-associated lymphoid tissue (GALT) is an important early site for human immunodeficiency virus (HIV) replication and severe CD4 + T-cell depletion, our understanding is limited about the restoration of the gut mucosal immune system during highly active antiretroviral therapy (HAART). We evaluated the kinetics of viral suppression, CD4 + T-cell restoration, gene expression, and HIV-specific CD8 + T-cell responses in longitudinal gastrointestinal biopsy and peripheral blood samples from patients initiating HAART during primary HIV infection (PHI) or chronic HIV infection (CHI) using flow cytometry, real-time PCR, and DNA microarray analysis. Viral suppression was more effective in GALT of PHI patients than CHI patients during HAART. Mucosal CD4+ T-cell restoration was delayed compared to peripheral blood and independent of the time of HAART initiation. Immunophenotypic analysis showed that repopulating mucosal CD4+ T cells were predominantly of a memory phenotype and expressed CD11α, αEβ7, CCR5, and CXCR4. Incomplete suppression of viral replication in GALT during HAART correlated with increased HIV-specific CD8+ T-cell responses. DNA microarray analysis revealed that genes involved in inflammation and cell activation were up regulated in patients who did not replenish mucosal CD4+ T cells efficiently, while expression of genes involved in growth and repair was increased in patients with efficient mucosal CD4+ T-cell restoration. Our findings suggest that the discordance in CD4+ T-cell restoration between GALT and peripheral blood during therapy can be attributed to the incomplete viral suppression and increased immune activation and inflammation that may prevent restoration of CD4+ T cells and the gut microenvironment.

Original languageEnglish (US)
Pages (from-to)8236-8247
Number of pages12
JournalJournal of Virology
Volume80
Issue number16
DOIs
StatePublished - Aug 2006

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Human immunodeficiency virus 1
mucosa
HIV-1
Mucous Membrane
T-lymphocytes
T-Lymphocytes
therapeutics
Highly Active Antiretroviral Therapy
Infection
infection
digestive system
HIV infections
Lymphoid Tissue
HIV
Human immunodeficiency virus
Therapeutics
Virus Diseases
Microarray Analysis
virus replication
Oligonucleotide Array Sequence Analysis

ASJC Scopus subject areas

  • Immunology

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Viral suppression and immune restoration in the gastrointestinal mucosa of human immunodeficiency virus type 1-infected patients initiating therapy during primary or chronic infection. / Guadalupe, Moraima; Sankaran-Walters, Sumathi; George, Michael D.; Reay, Elizabeth; Verhoeven, David; Shacklett, Barbara; Flamm, Jason; Wegelin, Jacob; Prindiville, Thomas P; Dandekar, Satya.

In: Journal of Virology, Vol. 80, No. 16, 08.2006, p. 8236-8247.

Research output: Contribution to journalArticle

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