SILCAAT and ESPRIT: taking stock.
HIV infection (Research)
T cells (Physiological aspects)
T cells (Research)
Antiviral agents (Health aspects)
|Publication:||Name: Journal of HIV Therapy Publisher: Mediscript Ltd. Audience: Academic Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2010 Mediscript Ltd. ISSN: 1462-0308|
|Issue:||Date: March, 2010 Source Volume: 15 Source Issue: 1|
|Topic:||Event Code: 310 Science & research|
|Product:||SIC Code: 2834 Pharmaceutical preparations|
|Geographic:||Geographic Scope: United Kingdom Geographic Code: 4EUUK United Kingdom|
Shortly after the HIV epidemic became established, it was a
strongly held view that the only thing that mattered for understanding
HIV pathogenicity was a falling CD4 cell count, as it was this that led
to the opportunistic infections and ultimately to death. As we began to
understand more about the virus itself and became able to measure its
levels accurately, it was commonly remarked that it was 'the virus
stupid', implying that the CD4 cell count was irrelevant.
Our understanding of the complexities and the pathogenesis of HIV have increased enormously in the last 20 years or so. I think the results of the SILCAAT and ESPRIT studies reported in this issue of the Journal of HIV Therapy would have surprised many of the early workers greatly. IL-2 induced a very considerable rise in CD4 cell count in both groups of patients, and yet there was no clinical benefit. The French had in fact licensed IL-2 on the grounds that those with low CD4 cell counts at therapy initiation achieved a more rapid CD4 cell count rise when given this drug. It may of course be that the CD4 cells that are produced in response to IL-2 do not work properly, and this is discussed in detail in this issue. It is also possible that the CD4 cell is really a surrogate marker for other important immunological changes that occur during HIV infection and which are not corrected by IL-2 treatment.
An almost bewildering array of new immunological data are emerging that may significantly improve our understanding of AIDS pathogenesis and, indeed, of the pathogenesis of a number of other diseases associated with HIV infection, such as atheroma and the increased risk of non-AIDS-defining cancers.
There has been an increasing interest in T regulatory cells that are also diminished in HIV infection and which are, in fact, stimulated by IL-2. There is also considerable interest in the rapid depletion of central memory cells from the lamina propria of the gut within days of acute seroconversion. The importance of [gamma][delta] cells and of T17 cells in this process remain to be elucidated. It is also unclear whether HAART can restore these cells in the lamina propria to more normal numbers and more normal function.
Recent papers indicate the potential importance of another cytokine, T18, in the genesis of atheroma. Indeed, the role of monocytes and macrophages responsible for scavenging lipids from atheromatous plaques are also the subject of intense investigation.
It is an exciting time for immunologists, and the study of HIV continues to be a way of gaining in-depth insight into many other disease processes. I do hope you will enjoy this issue of the journal as much as I have.
Consultant and HIV/GUM Research Director, Chelsea and Westminster Hospital, London, UK
Correspondence to: Brian Gazzard, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, UK
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