Hi!

I am looking for an AIDS catalog, which I got at Christmas and
subsequently threw out with 5000 other catalogs I got at Christmas.

But I meant to keep this one….

It was all AIDS products (ie cards and stationery, ribbons, videos,
t shirts etc…..) and all proceeds (or most proceeds?) go to AIDS
organizations….

Can anyone please email me (or post here) the phone number for this
catalog?  Sorry I don’t remember the name of it.. But if you’ve seen
it, you’ll know what I’m talking about….

Thanks in advance,

Jeanne
mirab…@eden.rutgers.edu

I’d promised myself I would never post again on this newsgroup but just
skim it for stuff that didn’t involve bitching between the different camps.
I just wanted to post something factual that nobody can deny/challenge,
because it is my personal experience.

I had the chance, near the beginning of the use of AZT for HIV+ people, to
get the drug. I declined. For me the stuff was indeed just a poison. There
seemed little proof (particularly back then) of it having any real effect.
Most importantly, the people I knew who were taking it did not seem to feel
better at all. On the contrary most of them seemed to feel worse. I am not
medicallly trained etc… but I have survived ca 12 years of being positive
going by the basic rule "If it makes people/me feel better it’s good. If it
makes people/me feel worse, it’s not good". I am certainly not a friend of
medication for its own sake and believe that ANY medication will have it’s
pros and cons.

Recently, I have found that friends who have been taking one of the PI
based triple combos have nearly all reported feeling ‘a lot better’. I have
seen that many of them have put on weight that they were losing hand over
fist. I have seen people who were definitely go downhill seem to perk up
and get involved in life again. This was more important in my decision of
whether to start treatment than any study, reference or blood count. I
started the treatment recently.

I have to say that I have more energy now than I have had in years. I feel
better in areas where I had not even noticed that I was feeling worse. My
appetite is back, I’m putting on weight etc etc. I do not say I am cured
and I do not say what is causing the ‘feeling better’. I simply report
that, my experience with the PI combos has been very good both in others
who are taking it and in myself.

There is probably a huge placebo effect involved etc and there are
arguments for many different theories that will be supported or attacked by
this posting. I have absolutely no opinion on those discussions. I am just
telling everyone what I personally have experienced.

Andy

Hey you two – and I think you know who… Here is a quote I thought you
might get a kick out of.

> The trouble with the rat race is that even if you win, you’re still a rat. – Lily Tomlin

Have a good day guys,
Adena

I thought that would confuse myself

SPAM

I am looking for ANY information on a rare and fatal blood disorder called
                                        thrombotythemia
It is where there are too many platelets. I have been unsucessful thus far
trying to retrieve any information. It may also be under      
myeloproliserative.
Please send any info to my e-mail address at msjt…@aol.com
Sincere thanks.

I have recently come across a few references to a conference that took
place in Washington DC (February 1989), titled, "AIDS – Defying the Odds
– Living Long and Lving Well: A Case for Optimism."

I would very much like to hear from anyone who knows anything about the
conference.There are a few summaries that I have found so far, both
printed in the Journal of Traditional Acupuncture (Summer 1989). From the
sound of it, the conference was quite encouraging. From one summary:

"First of all, we [the attendants] discovered that of the one hundred
people attending the Conference who had been diagnosed as HIV-positive –
some who had full AIDS – several had turned the disease around and are
now HIV-negative. All HIV-positive persons doing well had committed to do
everything they could to help themselves to health."

"The conference also underscored the great importance of practitioners of
all the healing arts sharing together, without personal interest, in the
service of patients."

In another article (by Harris Dienstfrey), there is an extremely
interesting examination of "how medical change (perhaps most change)
comes about, and intrinsic marits and word of mouth have little to do
with it." It is very thought-provoking. Originally the author was of the
belief that the values of alternative therapies would be self-evident:
that as people were healing, word of mouth, personal testimonies and
public events (such as the AIDS conference) would get the information to
the public.

The "largely echo-less aftermath of a singularly important conference on
AIDS" is one of the things that made him rethink his belief (admittedly
idealistic) that success itself would carry alternative therapies to the
public.

In another article in the same issue, there is an interesting story on
the work of Dr. George F Solomon, professor of psychiatry at the U. of
California. He s looking at the PNI factors associated with long-term
survval. So far, he has found one very intriguing thing.

Solomon:"The strongest correlation with positive immune factors in long
survivors with AIDS was an affirmative answer to one single question that
I devised … The single question is this: Will you refuse to do an
unwanted favor? [By 'unwanted favor' Solomon means a favor the person
does not want to do.] It [the question] really taps several things. It
taps assertiveness, the ability to say no, the ability to not become
overburdened, not to be masochistic and self-sacrificing, and to take
care of oneself, one’s own needs … We have other mini-correlation in
the AIDS studies, but that’s the strongest."

I’ll have more later.

Greg

Interesting comments by Dr. Donald I. Abrams, San Francisco General
Hospital, on antiretrovirals, protease inhibitors and HIV. Abrams has
been a key player in the HIV drug studies from day #1 of the epidemic.

Now the blame is put where it belongs: the anti-viral drug "activists"
!!!

No further commentary is needed in this tragedy of all tragedies…

=================================

The following excerpts are from an article published in the University
of California San Francisco publication "Synapse," dated October 10,
1996, volume 41, number 6, pages 1,5.

The title of the article is "Abrams Cautious On Use of New AIDS Drugs"
written by Mark Tanaka.

With guarded optimism, the Director of the AIDS program at SFGH
addressed a small group of medical students on Monday, Oct. 7, in HSW
300 on the subject of protease inhibitors, a much-publicized form of
anti-HIV therapy. Donald I. Abrams, Professor of Medicine, made use of
slides with graphs and charts as he interpreted the available
information for his student audience.

. . .

Nevertheless, protease inhibitors have raised many hopes, prompting many
HIV-positive people to reexamine their lives–without assuming they
would be dead in a few years. While sharing the optimism of many
patients and scientists, Abrams seemed cautious. "In contrast with many
of my colleagues at SFGH in the AIDS program, I am not necessarily a
cheerleader for anti-retroviral therapy. I have been one of the people
who’s questioned, from the beginning, whether or not we’re really making
an impact with HIV drugs and, if we are making an impact, if it’s going
in the right direction."

Despite the promising evidence, definitive proof of protease inhibitors’
efficacy can be provided only by randomized clinical trials with
placebo. Because new antiviral drugs are continuously being developed,
conducting such trials is virtually impossible due to the reluctance of
patients to continue treatment with and "old" drug. Abrams spent the
first half of his lecture describing analogous problems during the
testing and approval of AZT, the first drug used in AIDS therapy.

AZT, a nucleoside analog, belongs to a class of drugs that inhibit DNA
polymerization by terminating growing DNA chains. The study which
demonstrated that AZT might be of benefit was a placebo control trial
begun in 1986 involving 288 patients. Although the study was originally
intended to last 24 weeks, it was cut short and unblinded half way
through because of statistically significant differences in deaths
between the two groups.

Abrams lamented that although "18 more people made it to this arbitrary
milestone of four to eight months after pneumocystis… I didn’t feel
that this was showing that we were prolonging survival." Abrams blamed
the "very powerful rhetoric" of the emerging community of AIDS
activists, who demanded an end to clinical trials. "Somebody should
write a book about the impact of that decision on HIV clinical trials
history," added Abrams "because everything changed because of that
demand."

. . .

Abrams recounted his early misgivings about AZT, which loses its effect
after a year or two because the virus becomes resistant. He was also
disturbed by findings demonstrating that a high dose of AZT resulted in
a smaller rise of CD4 cells than a lower dose. "Maybe if we just stop it
altogether people will be better off," he said.

Members of the audience were surprised to learn of the paucity of solid,
clinical research behind AZT and other nucleic acid chain terminators,
which prevent infected T-cells from transcribing the RNA viral genome
into DNA, thereby inhibiting viral pathogenesis. Abrams exposed the
tragic farce of past AIDS research and therapy–people who thought they
were doing something useful were actually wasting time and valuable
resources.

. . .

How should the clinician apply the new therapies? Abrams described
his approach with patients. "I have a large population of people who
have chosen not to take any antiretrovirals since I’ve been following
them–since the very beginning… They’ve watched all of their friends
go on the antiviral bandwagon and die, so they’ve chose to remain naive
[to therapy]. More and more, however, are now succumbing to pressure
that protease inhibitors are ‘it’… We are in the middle of the
honeymoon period, and whether or not this is going to be an enduring
marriage is unclear to me at this time, so, I’m advising my patients if
they still have time, to wait."

The talk was given as part of the Horizons Lecture Series, organized by
second year medial student Nicholas Vogenthaler.

Interesting article in the Annals of Internal Medicine that further
undermines CD4 counts and viral load as surrogate markers of disease
progression and antiviral drug efficacy.

——————–

Fleming TR, DeMets, DL. Surrogate end points in clinical trials: Are we
being
Misled? Annals of Internal Medicine, 1996 Oct 1, 125:605-613.

Abstract: Phase 3 clinical trials, which evaluate the effect that new
interventions have on the clinical outcomes of particular relevance to
the
patient (such as death, loss of vision, or other major symptomatic
event),
often require many participants to be followed for a long time. There
has
recently been great interest in using surrogate end points, such as
tumor
shrinkage or changes in cholesterol level, blood pressure, CD4 cell
count or
other laboratory measures, to reduce the cost and duration of clinical
trials. In theory, for a surrogate end point to be an effective
substitute
for the clinical outcome, effects of the intervention on the surrogate
must
reliably predict the overall effect on the clinical outcome. In
practice,
this requirement frequently fails. Among several explanations for this
failure is the possibility that the disease process could affect the
clinical
outcome through the surrogate, with the intervention’s effect on these
pathways differing from its effect on the surrogate. Even more likely,
the
intervention might also affect the clinical outcome by unintended,
unanticipated, and unrecognized mechanisms of action that operate
independently of the disease process. We use examples from several
disease
areas to illustrate how surrogate end points have been misleading about
the
actual effects that treatments have on the health of patients. Surrogate
end
points can be useful in phase 2 screening trials for identifying whether
a
new intervention is biologically active and for guiding decisions about
whether the intervention is promising enough to justify a large
definitive
trial with clinically meaningful outcomes. In definitive phase 3 trials,
except for rare circumstances in which the validity of the surrogate end
point has already been rigorously established, the primary end point
should
be the true clinical outcome.

Page 610: HIV Infection and AIDS. The use of surrogate end points has
probably been more intensely discussed in the design and analysis of
clinical
trials of HIV infection and AIDS than in any other area. In a review of
AIDS
trials, Fleming summarized results from the largest trials that
evaluated
effects of nucleoside analogues on surrogate end points and clinical
outcomes. The summary of results from a 1993 state-of-the-art conference
shows that the effect of treatment on the most popular surrogate, the
CD4
cell count, did not accurately predict the effect of treatment on the
clinical outcomes, that is progression to AIDS or time to death.

In this review, which involved 16 major AIDS trials, the surrogate end
point
of CD4 cell count was significantly favorable in 7 of the 8 trials in
which
treatment improved the clinical outcome of progression to AIDS or death.
Unfortunately, the CD4 cell count was significantly favorable in 6 of
the 8
trials in which treatment did not improve progression to AIDS or death.
For
survival, the CD4 cell count was significantly favorable in only 2 of 4
trials in which treatment showed a significantly favorable effect on
survival
and, even worse, was significantly favorable in 6 of 7 trials in which
treatment had no effect on survival. Three additional trials, including
the
Concorde Trial showed an inverse relation between survival and improved
CD4
cell counts.

The Concorde Trials involved 1749 asymptomatic HIV-positive patients who
were
randomly assigned to receive immediate or deferred treatment (when
symptoms
occurred) with zidovudine. During a follow-up period of 3 years, the
decline
in CD4 cell counts was slowed by immediate zidovudine therapy, with an
average difference of 30 to 35 cells/mm^3 between the two treatment
groups.
In addition, patients in the group that received deferred treatment with
zidovudine more quickly achieved a 50% decline in CD4 cell counts.
However,
the clinical outcomes did not reflect these changes in the surrogate end
point. Time of progression to AIDS-related complex, AIDS or death was
essentially unaffected (175 event in the immediate zidovudine treatment
group
compared with 171 in the delayed zidovudine treatment group). For death
alone, the results actually favored the delayed zidovudine treatment
group
(95 compared with 76 deaths). The early pressures to use zidovudine
treatment
in asymptomatic persons with HIV were not supported by these longer-term
clinical events.

Page 611. Conclusions. Effects on surrogate end points often do not
predict
the true clinical effects of interventions. Although there are many
explanations for this failure, such as the existence of causal pathways
of
the disease process that are not mediated through the surrogate end
point and
that might be influenced differently by the intervention, the most
plausible
explanation is usually that the intervention has unintended mechanisms
of
action that are independent of the disease process. These unintended
mechanisms can readily cause the effect on the true clinical outcome to
be
inconsistent with what would have been expected solely on the basis of
evaluation of surrogate end points. These mechanisms are insidious
because
they are often unanticipated and unrecognized.

Unfortunately, the failure of surrogate end points to predict true
outcome is
not an isolated problem. Table 1 [see excerpt below] shows various
examples
from several disease and treatment and prevention strategies, including
many
comprehensive meta-analyses that involve scores of clinical trials.
Several
other examples of the failure of surrogate end points can be seen in
other
settings, ranging from trials of vaccines that use the presence of
neutralizing antibodies or cell-mediate immune response as the surrogate
end
point, thrombolytic agent trials that use vessel repercussion, and
cancer
screening strategies that use stage of detected disease to trials of
vitamin
supplementation for treatment of retinitis pigmentosa using decline of
electroretinograms as the surrogate end point, oxygen supplementation in
severe chronic obstructive pulmonary disease using physiologic
variables,
dental treatments using probing attachment levels, and surgery using
excision
of disease or establishment of the blood flow.

The validity of a surrogate end point has rarely been rigorously
established.
Occurrence of false-positive and false-negative results must be low,
typically in the range of 2.5% to 10%, in definitive trials evaluating
the
effects of interventions on clinical outcomes. Hence, to be a valid
replacement end point, a surrogate must provide a high level of accuracy
in
predicting the intervention’s effect on the true clinical end point.
Predictions having an accuracy of approximately 50%, such as the
accuracy
seen with the CD4 count in the HIV setting, are as uninformative as a
toss of
a coin. Methods for validation surrogate end points have been discussed
by
Lin and colleagues, Freedman and associates, and DeGruttola and
colleagues.
Statistical methods for validation usually require meta-analyses because
the
sample sizes needed are much larger than those required for the typical
phase
3 evaluation of interventions. Proper validation of surrogates also
requires
an in- depth understanding of the causal pathways of the disease process
as
well as the intervention’s intended and unintended mechanisms of action.
Such
insights are rarely achievable.

Surrogate end points should be used where they perform best–in
screening for
promising new therapies through evaluation of biological activity in
preliminary phase 2 trials. Such results in turn can guide decisions
about
whether the intervention is sufficiently promising to justify the
conduction
of large-scale and longer-term clinical trials. Although information on
surrogate end points in these definitive phase 3 trials can provide
further
valuable insight into the intervention’s mechanisms of action, the
primary
goal should be to obtain direct evidence about the intervention’s effect
on
safety measures and true clinical outcomes.

——————–

Page 607: From Table 1, titled "Speculation on Reasons for Failures of
Surrogate End Points."

For HIV infection or AIDS, with the intervention of antiretroviral
agents,
using the surrogate end points of CD4 levels and viral load, and the
clinical
endpoints of AIDS events or survival, the authors state that the likely
or
plausible reasons for failure of surrogate end points are (1) of several
causal pathways of the disease, the intervention only affects the
pathway
mediated through the surrogate; (2) the surrogate is not in the pathway
of
the intervention’s effect or is insensitive to its effect; and (3) the
intervention has mechanisms of action that are independent of the
disease
process.

I originally posted this on July 25, 1996 on misc.health.aids.

I again offer this item to illustrate how the AIDS treatment
community has again been fooled by those they desperately want
to believe (AIDS researchers, drug activists, etc…).

WFS (2/2/97)

=================
Science, Vol 273, July 19, 1996 Page 302 reports:

A patient "whose lymph and blood appeared virus-free adter 78
weeks of taking a drug combination, decided to stop the treatment.
Within 1 week, high levels of virus could be found in the blood."

meanwhile…

Aaron Diamond director David Ho estimates that "30 to 120"
weeks if potent drug treatment will be needed to "clear the virus."

What’s going on? Why was the fast viral rebound after 78 weeks?

Are these just garden-variety immune suppressors? Is the virus
actually burning hotter through cell-to-cell transmission when
these drugs are being used (as may be suggested in apoptotic
interference)? Are these drugs making the patient’s disease
progress or are they really slowing it down?

Something very funny is going on here.

W. Fred Shaw

Jay A. Levy, M.D., one of the leading researchers of HIV
disease from the University of California School of Medicine,
San Francisco, presents his viewpoint in JAMA regarding the
controversy surrounding the value of the surrogate markers when
they are valid (modified by the natural cellular immune
response) versus when they are invalid (altered by drug
regimens in ways that do not confer a corresponding long-term
clinical benefit, e.g. redistribution from lymph tissue seen in
antiretroviral and protease inhibitor treatments, as well as
interference with apoptosis as seen in IL-2 therapy, etc.).

This controversy goes to the very heart of the clinical trials
which have used, and continue to use, these surrogate markers
to determine statistical clinical “endpoints”, and therefore,
dramatic claims for “improved survival”.

As one well-known senior NIH researcher rhetorically, but
succinctly, points out in support of Levy’s position (personal
communications, 11/96):

    “Where are the brains of these AIDS researchers????”

Indeed.

W. Fred Shaw

—————————————–
Journal of the American Medical Association,
Oct. 16, 1996, Vol 276, No.15, Letters, p1219-1220

The response by Drs. Kinloch-de-Loes and colleagues to my
Controversies reiterates the difficulty in knowing whether
surrogate markers give a true insight into a clinical benefit.
I maintain my premise that drug therapy should mimic the
natural cellular immune responses associated with low viral RNA
to control HIV and sustain a long-term asymptomatic course.
Kinloch-de-Loes et al emphasized neutralizing antibodies, but
these most likely have no effect on a clinical course: the
cellular immune response is the major component in preventing
progression to disease. My emphasis has been on approaches to
increase this cellular immune activity, which can control HIV
by a variety of mechanisms, particularly suppression of virus
replication.(1) This comment, however, does not negate the
conclusion by Kinloch-de-Loes et al (with which I agree) that a
treatment regimen needs to be judged by its clinical
effectiveness, not by any particular measure, although the
reason for the effectiveness may give insight into other
approaches to control HIV infection.

My comments on the monthly improvement of CD4+ cells were meant
to emphasize that measuring this factor alone, particularly
with such small increases in number after therapy, has not
provided convincing evidence of clinical relevance. To cite the
“statistical” importance of the results described is merely to
underline my concern that statistics should not be expected to
give conclusive answers to biological phenomena. The
relationship of low CD4+ cell counts to the clinical state has
been well established, but whether this factor has merit under
treatment has been questioned by several investigators besides
me.

Moreover, to comment that most HIV-infected patients would
rather have a treatment-induced excess of 0.137 X 10^9 CD4+
cells than not may be true only if there is no substantial
toxicity associated with that therapy. Once again, emphasizing
CD4+ cell counts without long-term clinical benefit could be
misleading, as we learned from the Concorde study. (2)

Finally, I do not understand the reference of Kinloch-de-Loes
et al to Rose’s “prevention paradox,” which does not let us
understand whether the improvement in 1 surrogate marker
reflects the real reason for clinical benefit. Their example,
an overall reduction of diastolic blood pressure of 5 mm Hg,
appears to be a surrogate marker for what may reflect a more
meaningful factor that has not been considered in the analyses.
What does an average say about individual indexes? In the case
of HIV, an increase in the CD4+ cell count at the expense of
quality of life with no long-term clinical benefits does not
have much merit. One major concern is that this induced
increase in CD4+ cells could recruit and therefore deplete the
pool of CD4+ cells within lymphoid tissues. Thus, a momentary
improvement in CD4+ cell count and clinical state may take
place, but not the long-term clinical benefit that might be
achieved by allowing or inducing the immune system to respond
to the infection.

Jay A. Levy, M.D.
University of California School of Medicine
San Francisco

1. Levy JA, Mackewicz CE, Barker E. Controlling HIV
pathogenesis; the role of noncytotoxic anti-HIV activity of
CD8+ cells. Immunology Today. 1996:17:217-224.

2. Seligmann M, Warell DA, Aboulker JP, et al. Concorde:
MRT/ANRS randomized double-blind controlled trial of immediate
and deferred zidovudine in symptom-free HIV infection. Lancet
1994; 348:871-881.