Both CD31+ and CD31- Naive CD4+ T Cells Are Persistent HIV Type 1-Infected Reservoirs in Individuals Receiving Antiretroviral Therapy

• Published in: The Journal of infectious diseases Vol. 202; no. 11; pp. 1738 - 1748
• Main Authors: Wightman, Fiona, Solomon, Ajantha, Khoury, Gabriela, Green, Justin A., Gray, Lachlan, Gorry, Paul R., Ho, Yung Shwen, Saksena, Nitin K., Hoy, Jennifer, Crowe, Suzanne M., Cameron, Paul U., Lewin, Sharon R.
• Format: Journal Article
• Language: English
• Published: Oxford The University of Chicago Press 01.12.2010; University of Chicago Press; Oxford University Press
• Subjects: Adult; Anti-Retroviral Agents - pharmacology; Arts; Biological and medical sciences; Blood cells; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - virology; Cell growth; Cross-Sectional Studies; DNA; Female; Flow Cytometry; Fundamental and applied biological sciences. Psychology; HIV; HIV 1; HIV Infections - blood; HIV Infections - drug therapy; HIV-1 - drug effects; HIV-1 - genetics; HIV/AIDS; Human viral diseases; Humans; Infections; Infectious diseases; Longitudinal Studies; Male; Medical sciences; Memory; Microbiology; Miscellaneous; Platelet Endothelial Cell Adhesion Molecule-1 - analysis; Polymerase Chain Reaction; Regression Analysis; Singapore; T lymphocytes; Victoria; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Virology; Viruses; Immunopathology; Antiretroviral agent; CD4 T lymphocyte; HIV-1 virus; Retroviridae; AIDS; Immune deficiency; Lentivirus; Virus; Infection; Treatment; Viral disease; Antiviral; Human immunodeficiency virus
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1086/656721

Background. Naive T cell recovery is critical for successful immune reconstitution after antiretroviral therapy (ART), but the relative contribution of CD31+ and CD31- naive T cells to immune reconstitution and viral persistence is unknown. Methods. In a cross-sectional (n = 94) and longitudinal (n = 10) study of human immunodeficiency virus (HIV)-infected patients before and after ART, we examined the ratio of CD31+ to CD31- naive CD4+ T cells. In the longitudinal cohort we then quantified the concentration of HIV-1 DNA in each cell subset and performed single-genome amplification of virus from memory and naive T cells. Results. Patients receiving ART had a higher proportion of CD31+ CD4+ T cells than HIV-1-infected individuals naive to ART and uninfected control subjects (P < .001 and .007, respectively). After 24 months of ART, the proportion of CD31+ naive CD4+ T cells did not change, the concentration of HIV-1 DNA in memory CD4+ T cells significantly decreased over time (P < .001), and there was no change in the concentration of HIV-1 DNA in CD31+ or CD31- naive CD4+ T cells (P = .751 and .251, respectively). Single-genome amplification showed no evidence of virus compartmentalization in memory and naive T cell subsets before or after ART. Conclusions. After ART, both CD31+ and CD31- naive CD4+ T cells expand, and both subsets represent a stable, persistent reservoir of HIV-1.