1. ¹Centre for Immunology, St Vincent's Hospital, Sydney, Australia
2. ²National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, New South Wales, Australia

Correspondence: Dr AD Kelleher, National Centre in HIV Epidemiology and Clinical Research, Level 2, 376 Victoria St, Darlinghurst, Sydney, NSW 2010, Australia. E-mail: t.kelleher@cfi.unsw.edu.au

Received 25 September 2006; Revised 10 October 2006; Accepted 19 October 2006; Published online 5 December 2006.

Abstract

Human immunodeficiency virus (HIV) infection causes chronic progressive immunodeficiency and immune dysregulaton. Although simple depletion of the major target of HIV infection, the CD4+ T cell, can explain much of the immunosuppression seen, there are multiple other factors contributing to the immune dysregulation. CD4+ T-cell depletion induces a range of homeostatic mechanisms that contribute to immune activation and cell turnover, providing a milieu conducive to further viral replication and cell destruction, resulting in functional defects in various lymphoid organs. These changes are progressive and in turn compromise the homeostatic processes. Further, the infection, like any other viral infection, provokes an active immune response consisting of both CD4+ and CD8+ T-cell responses. Both appear compromised, displaying aberrant memory cell production. While some of these defects result from viral variation and the chronicity of antigen presentation, other defects of memory cell production appear very early during the primary immune response limiting the viral specific T-cell responses from the outset. This, combined with the ability of the virus to escape any successful immune responses, results in an attenuated immune response that eventually becomes exhausted, characterized by progressive deficits in T-cell repertoire. Furthermore, negative regulatory mechanisms that normally control the immune response may be aberrantly invoked, perhaps directly by the virus, further compromising the efficacy of the immune response. Rational design of effective immunotherapies depends on a clear understanding of the processes compromising the immune response to HIV.