From: Billi Goldberg <bigoldberg@igc.apc.org>
Subject: Disease Progression and CTLs in AIDS
Note: Copyright 1992, Dan R. Greening. Non-commercial reproduction allowed.
Archive-Number: 6
Organization: unspecified
Date: Wed, 20 Jan 93 23:49:57 PST

The following article was printed in the San Francisco Sentinel on 
Thursday, January 21, 1993. There are no restrictions on reproduction of 
this article according to the author Charles R. Caulfield and the San 
Francisco Sentinel.

*********************************************************************** 
            Cytotoxic T-Cells and Disease Progression in AIDS
                       by Charles R. Caulfield

CD4 T-Lymphocytes have long been considered the most significant markers 
of disease progression in AIDS with declines in their number being 
considered predictive of the onset of opportunistic infections. It was 
considered a breakthrough in AIDS research when CD4 T-Cell numbers were 
allowed to substitute for death in clinical trials, gaining them the 
dubious title of "surrogate markers."

Recent research at state of the art research centers indicates that CD8 
T-cells, also known as cytotoxic lymphocytes play a most crucial role in 
determining the immune status of the patient. Despite this, many 
physicians in clinical practice are reticent to let go of outdated 
measurements of disease progression in AIDS. Currently the most widely 
used laboratory predictors of disease progression have been the P-24 
antigen and antibody tests, beta 2 microglobulin, CD4 counts and 
neopterin levels, all of which are drawn from the blood. And yet it is 
clearly recognized by the medical community that the bulk of the viral 
infection, and that of the pathogens which are opportunistic in AIDS, 
reside primarily in the mucous membranes of the body, making blood 
laboratory evidence of dubious value.

The importance in maintaining CD8 counts is only recently becoming 
widely recognized in AIDS treatment. Two submissions for presentations 
at next years 9th International Conference on AIDS in Berlin, drawn from 
research in two entirely different fields of study have as their closing  
statements that a halting of disease progression is associated over 
periods of time with stable CD8 counts, despite possible declines in 
numbers of CD4s, even in some cases to zero. It is speculated in both 
papers that this may be a common denominator in long term survival as 
has been the long-held position of Dr. Jay Levy of UCSF.  But patients 
seldom ask their physicians for their CD8 counts,  and physicians seldom 
offer the information, even though it could afford the patient the 
option of considering a therapy aimed at  increasing the numbers of and 
stabilizing these critical cells.

Several approaches to increasing the numbers of CD8s in symptomatic 
individuals are under investigation. A KS treatment called CD8 
expansion, in which CD8 T-Cells are removed from the blood and 
cultivated in culture by adding the protein interleukin is currently 
fully enrolled and underway in San Francisco.  Another means of doing 
this is by modifying the body's biological response. Topical application 
of DNCB  has been consistently shown to nontoxically raise CD8 counts 
and natural killer cells among compliant patients, which would explain 
why this drug is receiving increasing attention among patients and 
physicians around the world.

What is needed is the technology to measure viral replication in 
mucosal tissue and in the lymphatic system where the greatest 
populations of virus and other pathogens reside. The science exists, in 
what is known as polymerase technology. A laboratory test called the 
Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) is the gold 
standard in determining the activity of the virus in the tissues, and 
therefore has incomparable value in assessing the effectiveness of drugs 
intended to interfere with viral replication. In addition to this, a 
subset of T-lymphocytes known as CD38s, which are in fact immature CD8s, 
have been shown to correspondingly increase in numbers with the clinical 
decline of the patient.

Why are these laboratory tests not being utilized in everyday use, even 
at leading Medical Centers? Many researchers, scientists and activists 
realize that this is one of the most critical issues in turning around 
12 years of bungling, and getting on the right track toward finding 
effective treatments quickly.  It is certain that there are those 
pharmaceutical industry profiteers who will not take too kindly to a 
revisionism resulting from what is currently being discovered in 
immunology. 

Our morbid preoccupation with certain 'magic' numbers in CD4 counts was 
certainly fostered back in 1987, when Burroughs-Wellcome set 200 CD4 as 
the required T-cell decline to qualify for AZT. Most current antiviral 
therapies for HIV use blood tests to evaluate their effectiveness, yet 
the substantial viral load is not in the bloodstream. It would appear 
that some very influential organizations and institutions would have a 
vested interest in disregarding the newest data, and using their 
enormous influence to see to it that most other people do the same.  
When it's life vs. profit, guess who wins.
************************************************************************

Charles Caulfield is a staff writer for the San Francisco Sentinel and 
was a board member of The National Association of People with AIDS 
(NAPWA) for five years. Charles was diagnosed in 1984 with PCP and has 
maintained his health through the use of safe and natural therapies and 
positive life changes. His works have appeared in the PWA Newsline, and 
Being Alive.
Newsgroups: sci.med.aids