Viral Suppression and Immune Restoration in the Gastrointestinal Mucosa of Human Immunodeficiency Virus Type 1-Infected Patients Initiating Therapy during Primary or Chronic Infection
- 15 August 2006
- journal article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 80 (16), 8236-8247
- https://doi.org/10.1128/jvi.00120-06
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 CD11 alpha, alpha(E)beta 7, 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.Keywords
This publication has 53 references indexed in Scilit:
- The Case for Earlier Treatment of HIV InfectionClinical Infectious Diseases, 2004
- Immune Activation and CD8+ T-Cell Differentiation towards Senescence in HIV-1 InfectionPLoS Biology, 2004
- Trafficking of Human Immunodeficiency Virus Type 1-Specific CD8+T Cells to Gut-Associated Lymphoid Tissue during Chronic InfectionJournal of Virology, 2003
- A Preponderance of CCR5+CXCR4+Mononuclear Cells Enhances Gastrointestinal Mucosal Susceptibility to Human Immunodeficiency Virus Type 1 InfectionJournal of Virology, 2001
- The Cost Effectiveness of Antiretroviral Regimens for the Treatment of HIV/AIDSPharmacoEconomics, 2000
- Lamina Propria Lymphocytes, Not Macrophages, Express CCR5 and CXCR4 and Are the Likely Target Cell for Human Immunodeficiency Virus Type 1 in the Intestinal MucosaThe Journal of Infectious Diseases, 2000
- The Impact of Early Initiation of Highly Active Antiretroviral Therapy on the Human Immunodeficiency Virus Type 1–Specific CD8 T Cell Response in ChildrenThe Journal of Infectious Diseases, 2000
- Human intestinal lamina propria lymphocytes are naturally permissive to HIV-1 infectionEuropean Journal of Immunology, 1999
- Loss of CD4 T lymphocytes in patients infected with human immunodeficiency virus type 1 is more pronounced in the duodenal mucosa than in the peripheral blood. Berlin Diarrhea/Wasting Syndrome Study Group.Gut, 1995
- Primary Acute Simian Immunodeficiency Virus Infection of Intestinal Lymphoid Tissue Is Associated with Gastrointestinal DysfunctionThe Journal of Infectious Diseases, 1994