February 13, 2003
In this presentation Dr. Fauci gave an overview of the pathogenesis of HIV infection and the impact of HIV viremia on CD4 cells, B cells, and natural killer (NK) cells. His presentation dealt extensively with the use of gene array systems to monitor the differences among these various cell types in HIV-infected versus non-infected individuals.
Dr. Faucis presentation showed that the induction of aberrant gene expression can be caused by HIV infection in these various cell types and that, in turn, this can lead to phenotypic abnormalities and functional deficits in the immune system. Dr. Fauci showed how these deficits are involved in HIV pathogenesis. It is extremely important that the use of antiretroviral drug regimens can reverse certain of these deficits and restore immune function.
In particular, Dr. Fauci focused on the role of HIV viremia in regard to the expression of receptors on natural killer cells that facilitate recognition of targets. Although the effects of HIV infection can be heterogeneous, a variety of cells are affected and can show modulation of their wild-type phenotypes. In particular, HIV replication may have dramatic consequences for immunological memory cells that may be compromised in regard to ability to remain functionally active. Dr. Fauci stressed that many of these effects are non-cytopathic for the cells of the immune system that are affected, but that both direct infection and infection-related events can play an important cumulative role in the process of HIV pathogenesis.
Dr. Fauci also demonstrated how cytokine production can be stimulated by normal B cells but, at the same time, how HIV infection can lead to a down-regulation of expression of certain heat-shock proteins associated with immune responsiveness and recognition by NK cells. In particular, interactions between B cells and T cells are compromised by HIV infection and this, in turn, can also lead to severe immunologic down-regulation.
It is also important to note that important distinctions were found among HIV-infected individuals who suffered from chronic viremia, regardless whether they were receiving HAART, versus individuals whose HAART regimens led to effective suppression of viral load and who were therefore non-viremic. In this context, it is possible that the release of virions can have important consequences in regard to immune cell function. In addition, microarray analysis showed that resting CD4 T cells from viremic patients expressed genes that were conducive to efficient viral replication, whereas such gene expression was less manifest in non-viremic subjects. The B cells from such individuals also demonstrated important abnormalities, including an inability to respond to T-cell signalling.
Hence, it is important for physicians to recognize the need to achieve suppression of viral replication through effective use of antiretroviral regimens. Failure to do so may lead to continuous viral replication, and the production of viruses by T cells can have direct and multi-factorial consequences for T cells, B cells, and NK cells. Dr. Fauci stressed that effective suppression of viral replication, regardless of regimen used, is essential to maintain immune capabilities and preserve effective immune responsiveness.