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edd lee

i have more of a question that a comment - how is an individual's level of immune activation measured currently? how accurate/useful are these measurements? thanks!

RJefferys

Hi Edd, the most studied immune activation marker is a molecule called CD38. Expression of this molecule on CD8 T cells appears to correlate quite strongly and reproducibly with CD4 decline and disease progression. The same holds true for expression of CD38 on CD4 T cells although fewer CD4 T cells express the molecule and the correlations are a little weaker. Some other markers of immune activation also correlate with disease progression, such as HLA-DR (another molecule expressed on activated T cells).

I have not yet confirmed as much with the researchers, but would hope that they are now conducting similar analyses to establish if CD38 (or any other marker of immune activation) can predict CD4 decline more reliably than viral load at the individual level. If so, there would be a strong case for advocating that the assay be commercialized for clinical use. For vaccines that might slow disease progression rather than fully protect against HIV infection, markers of immune activation might also have a role in predicting long-term vaccine efficacy. For example, a Steven Deeks study from a few years ago found that the T cell activation "set point" after acute infection predicted subsequent CD4 T cell decline:

http://www.bloodjournal.org/cgi/content/full/104/4/942

Additional studies that have evaluated CD38 expression as a correlate of disease progression include:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=9358102&query_hl=3&itool=pubmed_DocSum

Elevated CD38 antigen expression on CD8+ T cells is a stronger marker for the risk of chronic HIV disease progression to AIDS and death in the Multicenter AIDS Cohort Study than CD4+ cell count, soluble immune activation markers, or combinations of HLA-DR and CD38 expression.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=9052725&query_hl=3&itool=pubmed_DocSum

CD8+,CD38+ lymphocyte percent: a useful immunological marker for monitoring HIV-1-infected patients.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=8828739&query_hl=3&itool=pubmed_DocSum

Increased numbers of primed activated CD8+CD38+CD45RO+ T cells predict the decline of CD4+ T cells in HIV-1-infected patients.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=11012621&query_hl=3&itool=pubmed_DocSum

A single measurement of CD38+CD8+ T cells in HIV+, long-term surviving injecting drug users distinguishes those who will progress to AIDS from those who will remain stable.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=10068581&query_hl=3&itool=pubmed_DocSum

Shorter survival in advanced human immunodeficiency virus type 1 infection is more closely associated with T lymphocyte activation than with plasma virus burden or virus chemokine coreceptor usage.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15117448&query_hl=3&itool=pubmed_DocSum

CD8+CD38+ T cells but not HIV type 1 RNA viral load predict CD4+ T cell loss in a predominantly minority female HIV+ adolescent population.

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