HIV-1-infected CD8+CD4+ T cells decay in vivo at a similar rate to infected CD4 T cells during HAART

Hughes, Gareth Ja; Cochrane, Alexandraa; Leen, Cliffordc; Morris, Sheilac; Bell, Jeanne Eb; Simmonds, Petera

AIDS:
doi: 10.1097/QAD.0b013e3282f151b9
Clinical Science
Abstract

Objectives: To investigate the potential for CD4+CD8+ T cells [CD8 double positive (CD8 DP)] T cells to form a reservoir of HIV-1 following HAART through measurement of the rate of decay of infected CD4/CD8 DP T cells.

Methods: HIV-1 proviral loads in highly pure CD4 and CD8 DP T cells were determined for study subjects before and after 200–400 days of therapy and HIV-1 DNA decay rates were calculated.

Results: Before therapy, HIV-1 proviral load in CD8 DP correlated negatively with CD4 cell count. Decay rates of HIV-1-infected CD4 and CD8 DP T cells were similar. Rates for CD8 DP T cells correlated with the time to suppression of viral replication, whereas no such relationship was true for CD4 cell decay rates. A significant reduction in activated cells was observed for both cell types. The action of HAART on HIV-1 replication was similar for both CD4 cells and CD8 DP T cells, although the rate of clearance of infected CD8 DP T cells appeared more critical for a rapid reduction in plasma viral load. Although the size of the CD8 DP T cell reservoir in peripheral blood was smaller relative to that of CD4 cells, HAART did not completely clear HIV-1 infection from this cell subset.

Conclusion: This study confirmed that CD8 DP T cells are a major reservoir for HIV-1 in vivo and, therefore, represent a potential reservoir for HIV-1 during HAART, in a manner analogous to that of CD4 T cells.

Author Information

From the aCentre for Infectious Diseases, UK

bNeuropathology Unit, University of Edinburgh, UK

cRegional Infectious Diseases Unit, Western General Hospital, Edinburgh, UK.

Received 26 July, 2007

Revised 8 August, 2007

Accepted 17 August, 2007

Correspondence to Dr G. Hughes, Centre for Infectious Diseases, University of Edinburgh, Summerhall, Edinburgh EH9 1QH, UK. E-mail: gareth.hughes@ed.ac.uk

© 2008 Lippincott Williams & Wilkins, Inc.