THE FAUCI FILES, 3( 38): Anti-Retroviral Therapy (ART) Corporate Revisionism, Point-Counterpoint

W. Fred Shaw fredshaw at primenet.com
Wed Mar 8 17:28:29 EST 2000


THE FAUCI FILES, 3( 38): Anti-Retroviral Therapy (ART) Corporate
Revisionism, Point-Counterpoint

March 8, 2000

I am providing the following point-counterpoint analysis 
in response to Project Inform San Francisco's 
"Founding Director", Martin Delaney. As the leader of
the pharmaceutical Corporate "Treatment Activists", 
Mr. Delaney receives pharmaceutical funding and his 
periodic product editorial defenses, publications 
and lobbying efforts are obviously on behalf of the 
pharmaceutical industry.

Although Mr. Delaney and his organization claim to
represent a patient "constituency", it is worth noting
that Mr. Delaney's corporate commentary doesn't seriously
consider the negative health implications of ART 
for his purported constituency: the HIV/AIDS patient
(in fact, Mr. Delaney himself is HIV-negative).

Finally, it is also worth noting that Mr. Delaney's
Project Inform Board of Directors includes such luminaries
as Aaron Diamond's Dr. David Ho and Dr. Robert Gallo,
as well as others who have disclosed significant financial
conflicts of interest with the pharmaceutical industry.

W. Fred Shaw, Editor
THE FAUCI FILES
===============

Return-Path: <mary at aegis.org>
Message-Id:  <4.3.2.20000306230000.00dd4e10 at 127.0.0.1>
Date:        Mon, 06 Mar 2000 23:05:37 +0000
To:          "aids" <webmaster at aegis.com>
From:        "Sr. Mary Elizabeth, OSM" <mary at aegis.org>
Subject:     [AEGiS] Response commentary to Clerici article 
             posted March 5, 2000

>Submitted by Martin Delaney
>Project Inform
>--------------
>
>There is nothing either new or unusual about this.

Nothing could be further from the truth. 

> It is a phenomenon that has been reported and discussed repeatedly 
> among immunologists at meetings both privately and publicly. It does 
> not suggest a fault of therapy, but rather the success of it.

Again, nothing could be further from the truth.

FACT: this is the first time that a major scientist has separated 
those treated with antivirals from those who were antiviral
naive for the purpose of measuring, comparing and contrasting the 
immunological parameters of the ART-treated versus the ART-naive
(those who have never received ART treatment).

Although the Clerici et al article in the journal AIDS (1/28/00) 
was NOT an evaluation of the clinical relevancy or usefulness 
of ART therapy (personal communication), no true scientist of 
Clerici's impartial and ethical stature should ever participate 
in product research evaluations and recommendations.

Therefore, while remaining impartial as to the clinical usefulness
or validity of ART, Dr. Clerici et al nonetheless reports
objective findings that are rather startling and unambiguous:

  "Our results show that immune responses are potent in 
   antiretroviral-naive but significantly reduced in
   HAART-treated patients with undetectable viraemia (< 500 copies/ml)."

  "T-cell proliferation to HIV-specific and HIV-unrelated antigens is 
   potent in antiretroviral-naive but suppressed in HAART-treated 
   individuals; . . ."

  "Results: Results showed immune profiles to be profoundly different in
   antiretroviral-naive in comparison with HAART-treated patients. Thus:
     
     (1) T-cell proliferation to HIV-specific and HIV-unrelated antigens
         is potent in antiretroviral-naive but suppressed in 
         HAART-treated individuals; 

     (2) interleukin-(IL)2, IL-12 and interferon gamma (IFNgamma) 
         production is robust in naive patients; and 

     (3) a high CCR5/low CXCR4 pattern of HIV coreceptors-specific mRNA 
         is observed in naive but not in HAART-treated patients.

> It does not suggest a fault of therapy, but rather the success of it.

If one views immune suppression as a proper goal for a fatal
pathogenic disease with a symptomatic hallmark of immune suppression,
then ART is certainly a resounding, albeit deadly, "success".

> This reduction in the HIV specific immune response is a direct result
> of the reduction in viral replication as a result of therapy.

Nothing could be further from the truth. Immune suppression
by these ART drug therapies occurs independently of the
individual's viral load. Thus, the suppression of the entire 
immune response -- not merely the HIV-specific response -- 
is a primary and direct effect of these drugs rather than 
a downstream effect of viral reduction.

The reduction of ALL immune responses, including such things
as the candida and flu antigens (Clerici et al, AIDS, 1/28/00), 
were only observed in those using the ART drugs:

1. Treatment "failures" who use these ART drugs, achieve non-detectable
   viral loads but later experience viral rebound do NOT experience a 
   concomitant "rebound" in their HIV-specific immune response, as Mr. 
   Delaney suggests.

2. Treatment "failures" who use these ART drugs and do NOT achieve
   significant viral load reduction, will nonetheless suffer the same 
   ART-induced immune suppression as those who do achieve non-detectable
   viral loads. 

3. Treatment "naives" who never use these drugs and have low and 
   undetectable viral loads do NOT experience the loss of immune 
   responses -- HIV-specific or otherwise -- that are reported
   only for the ART-treated.

Mr. Delaney merely parrots the superstition promulgated by the
pharmaceutical industry that claims that these drugs are specific to
the HIV virus. Nothing could be further from the truth.

> What maintains that response in naive (untreated) patients 
> is the constant stimulation of the immune system by viral replication.

This focus on the HIV-specificity subset of the immune response
merely detracts from the immune response as a whole, which is clearly
being destroyed by the ART drugs.

FACT: The Clerici article clearly makes the unambiguous distinction 
between the HIV-specific and other immune responses:

   "T-cell proliferation to HIV-specific and HIV-unrelated antigens 
    is potent in antiretroviral-naive but suppressed in HAART-treated 
    individuals; . . ."

The reduction of HIV viral load does NOT account for the loss of
immune responses to other antigens, which were "defective"
ONLY in the ART-treated, such as the candida- and flu-specific
antigens.

> Once that is suppressed a few logs, the immune system no longer
> sees much HIV and therefore stops attempting to respond.

Rubbish. The immune systems of the ART-naive don't "stop
attempting to respond" when their viral load is "suppressed
a few logs" in the absence of these drugs. Further, as stated
above, those who use ART and do NOT achieve reductions in
viral load will nonetheless experience the same decline in
immune responsiveness as those who do achieve non-detectable
reductions in the HIV viral load.

>In people treated since the earliest stages of infection, it appears
>that this HIV specific immune response is sometimes preserved, or at
>least the capacity for making it.

At best, this statement is a very poor advertisement for using
these immune-destroying drugs for a disease of declining
immunity.

Clearly, ART suppresses ALL immune responses directly, NOT as a
secondary effect of reducing the HIV viral load. Terms such as 
"sometimes preserved" and "capacity for making" are, in this case, 
simple artifacts of Delaney's distance from the science.

> In some of the STI (therapy interruption) research, this response
> has been triggered after people go off therapy for a while.

Dr. Clerici et al detailed the overbroad suppression of
the immune response in the ART treated while the immune responses
of the ART-naive remain intact. Mr. Delaney offers no explanation 
for the intact immune responses of the treatment naive with 
low and undetectable viral load. 

Are the immune responses (HIV-specific and otherwise) of the 
treatment-naive suppressed in the presence of viral control? 
Of course not. Do the ART-naive retain their immunological
response to the flu and candida antigen? Yes.

Are the immune responses (HIV-specific and otherwise) of the 
ART treated suppressed in the presence of viral control? Yes. 
Do the ART-treated retain their immunological response to the 
flu and candida antigens? No.

(see references below) 

> Although the numbers are still relatively small, there is some 
> small, there is some indication that repeated cycles of on/off therapy
> can strengthen the natural immune response.

The claim that a "small number" or a "small indication" of
ART users who engage in "on/off therapy" will "strengthen the 
natural immune response" is made in the absence of comparative 
data involving the treatment naive. Such unscientific studies
in the absence of placebos or comparative data involving
those who are NEVER ART-treated have clearly dominated the
approval and recommendation process for these ART drug 
therapies for the past 13 years -- almost to the exclusion 
of anything else.

In fact, in this "small number" of those who use ART without
measurable loss of immune responses, Occam's Razor could favor only 
one conclusion: these individuals would have done the same or 
better had they not used the ART drugs in the first place.

> More than a dozen people are currently being studied who underwent 
> anywhere from one to three cycles of treatment interruption and 
> who now maintain undetectable viral load without further help from  
> antiviral drugs.

Absent a comparative group of treatment-naive, Delaney's "dozen people"
anecdote may be interesting, but offers little or nothing
in terms of scientific evidence, especially when we aren't 
being advised of the pre-treatment viral load of these
purported individuals.

To rely on such pie-in-the-sky studies after 13 years of these
toxic and dangerous pharmaceuticals as the "standard of care"
is as irresponsible as it is intentional in the deaths of those
who die as a direct result of using these drugs.

>It has also been noted that each time a treatment interruption cycle is
>used, it typically takes longer for viral load to become detectable
>again.

Obviously this observation could better be explained as an 
artifact of the cycles of ART-induced immune suppression, 
together with the dynamics of multi-drug resistance (MDR). 

>Until recently, this phenomenon had only been seen in people treated
>since primary infection. A new report was released at the VII
>International Retrovirus Conference which showed a similar outcome in a
>small number of chronically infected patients as well.

For the most part, the conference reports upon which Delaney relies
are little more than publicity stunts and appeals for drug company
research funding (they were never intended for peer-reviewed 
journal publication). The reliance on non-peer-reviewed and 
journal-unpublished anecdotal data from pharmaceutical conferences 
is not only typical of poor salesmanship, but clearly demonstrates the 
scientific and clinical bankruptcy of ART itself.

>Taken together, it might be suggested that the way to avoid loss of the
>HIV-specific response requires two steps.

Once again, the "HIV-specific" sales tactic avoids the most important 
issue: the overbroad loss of ALL immune responses, not merely those
related to HIV-specificity.

> First, it seems clear that the best chances for maintaining the 
> capacity to mount that response is to treat people early 

Mr. Delaney has struggled to make these issues anything but clear.

To use ART immune-suppressing drugs to suppress the immunological
control which, in the absence of these drugs, delays the 
onset of symptomatic disease for a decade or longer, could only 
portend a grim outlook for the patient.

Further, Mr. Delaney's lack of scientific candor is as abysmal as his
lack of scientific evidence to sustain the continued use of
the ART 13-year standard-of-care, which, as we can all plainly
see, has never been "standardized" nor has it offered "care"
in terms of preserving the competence of the innate immune response.

If a therapy for a disease of immune suppression fails to
protect and preserve the immune health of the patient, but
rather does harm to these life-critical protective processes,
then what good is it?

> (this, however, must be balanced against the earlier
> risks of side effects).

The early onset of "side effects" from ART "early use" is as
obvious as it is destructive of every tissue and organ system
of the body. Unfortunately, these "hit hard and hit early"
patients will most likely die of organ, vascular and/or a
variety of immune failures prior to the time they would be 
expected to develop AIDS. This can be seen in the preponderance
of obituary reports which reveal "sudden death" which is often
characterized as "not AIDS related". The very recent death 
of the Israeli Diva who died of "organ failure" offers a
case in point and begs an answer to the question that
arose after the approval of these ART drugs: what 
causes "organ failure" in those with HIV infection, if 
not the ART drugs?

> Secondly, preliminary data suggest that treatment needs to be 
> interrupted periodically to permit the virus to be
> "reintroduced" to the immune system periodically.

It was only a few short years ago that Mr. Delaney authored
an editorial in the Project Inform "PI Perspective", in
which he emphasized the life-critical importance of NEVER
missing a single dose of the ART regimen. Mr. Delaney's
precise words began with the alarmist admonition:

    "You have one chance to get it right ..."

Today, Martin Delaney is promoting the ART product line
with quite a different spin that underscores the
"benefit" of ART that is "interrupted periodically".

What corporate product spin will Delaney offer us a year
or two from now?

Further, as one of the favored corporate spins, the "potential
-but-not-quite-a-cure" sales tactic is not without precedent
(e.g. the implications for Delaney's latest spin on
the ART treatment theory: "permit the virus to be 'reintroduced' ... "),
as this was the original impetus for these drugs gaining
initial FDA approval in the first place. Aaron Diamond's 
Dr. David Ho (on Mr. Delaney's Project Inform Board of Directors)
played no small role in purveying this false treatment
claim in his 1996 claim for the ART "1 year cure", which
he later clarified as his "mathematical cure". Dr. Ho's 
superstitious claims have yet to materialize, however here 
they rematerialize in Delaney's own words that unambiguously 
imply that HIV virus "leaves the body" as a result of using
the ART drugs. Mr. Delaney, however, takes the superstition
to the next marketing level with the implication that
when the drugs are stopped, the virus will mysteriously be 
"reintroduced", as if that is something that is good, healthy
and desirable. Such is the nature of medical hucksterism.


To conclude this point-counterpoint analysis, it is essential
to re-examine the scientific rationale for Dr. Fauci's
ART "standard of care", which originally focused on
these drugs as potent weapons that would facilitate
the reconstitution of the immune response through the
decrease of the viral load, which, in turn, would
result in increases of the CD4+ T-cell count. (Interestingly, 
under NIAID Director Dr. Anthony Fauci's tutelage, Mr.
Delaney is listed by NIH/NIAID as a contributor to the development
of the ART "Standard of Care" recommendations, despite his
lack of medical or scientific credentials).

While Clerici et al, Pantaleo et al and others have recently
revealed that "HAART (ART) does not necessarily augment the 
immune response", then this can no longer be a rationale
for using HAART when the immune responses required
to control opportunistic infections and neoplasms are not 
only NOT being augmented, but to the contrary -- these
immune responses (e.g. including the flu and candida
antigens, Clerici et al, AIDS, 1/28/00) are being directly 
suppressed and harmed by ART!

Finally, the proposition that immunomodulators are needed
to "augment" ART is implicitly flawed when one considers
that these immunomodulators are merely needed to compensate
for the immune harm that is done by the first treatment (ART).

The treatment question remaining is obvious: can immunomodulators
even begin to compensate for the immune destruction done by ART,
and if so, wouldn't they be even more valuable in the control
of the HIV virus when they are used alone and in
the absence of ART, rather than as a medical intervention
that chases the harm done by ART, a therapy that can no
longer claim a valid "immune augmenting" rationale?

Isn't it rather revealing that these are the questions that
Mr. Delaney, Dr. Fauci, Dr. Ho and their various corporate
minions and sponsors are NOT bothering to ask for the betterment 
of what Delaney purports to be his "patient constituency"?

W. Fred Shaw, Editor
THE FAUCI FILES

========

The following articles by elite scientists, including Nobelist Rolf 
Zinkernagel, provide conclusive evidence that HAART: 

  (1) increases blood CD4 T-cells -- not by creating NEW CD4 T-cells,
      but rather by inducing the redistribution of the CD4 cells
      that are ALREADY present in the lymphoid tissues (thus,
      the lab CD4 measure becomes a superstitious treatment
      artifact of no true value).
  (2) increases CD4 T-cells which are suppressors, 
  (3) suppresses immune responses, 
  (4) suppresses cytokine production, and 
  (5) virological failure does not involve drug-resistant HIV-1 
      mutations:
 
(1) Bucy RP, Hockett RD, Derdeyn CA, Saag MS, Squires K, Sillers M, 
Mitsuyasu RT, Kilby JM. Initial increase in blood CD4(+) lymphocytes 
after HIV antiretroviral therapy reflects redistribution from lymphoid 
tissues. J Clin Invest 1999 May 15;103(10):1391-1398.

(2) HAART-induced increases in blood lymphocytes are of the CD4+ CD25+ 
phenotype (along with CD38 and CD44) (David Ho, 9th International 
Congress of Immunology, 1995), which are antigenic nonspecific 
suppressors (Thornton AM, Shevach EM. Suppressor effector function of 
CD4+CD25+ immunoregulatory T cells is antigen nonspecific. J Immunol 
2000 Jan 1;164(1):183-90). 

(3) Clerici M,* Seminari E, Suter F, Castelli F, Pan A, Biasin M, 
Colombo F, Trabattoni D, Maggiolo F, Carosi G, Maserti R (for the Master
Group). Different immunologic profiles characterize HIV infection in 
highly active antiretroviral therapy-treated and antiretroviral-naive 
patients with undetectable viraemia. AIDS 2000 Jan 28; 14:109-116.

(3) Soudeyns H, Campi G, Rizzardi GP, Lenge C, Demarest JF, Tambussi G, 
Lazzarin A, Kaufmann D, Casorati G, Corey L, Pantaleo G. Initiation of 
antiretroviral therapy during primary HIV-1 infection induces rapid 
stabilization of the T-cell receptor beta chain repertoire and reduces 
the level of T-cell oligoclonality. Blood 2000 Mar 1;95(5):1743-1751.

(3) Giorgi JV, Majchrowicz MA, Johnson TD, Hultin P, Matud J, Detels R. 
Immunologic effects of combined protease inhibitor and reverse 
transcriptase inhibitor therapy in previously treated chronic HIV-1 
infection. AIDS 1998 Oct 1;12:1833-1844

(3) Andre P, Groettrup M, Klenerman P, de Giuli R, Booth BL Jr, 
Cerundolo V, Bonneville M, Jotereau F, Zinkernagel RM, Lotteau V. An 
inhibitor of HIV-1 protease modulates proteasome activity, antigen 
presentation, and T cell responses. Proc Natl Acad Sci U S A 1998 Oct 
27;95(22):13120-13124 

(4) Al-Harthi L, Roebuck KA, Kessler H, Landay A. Inhibition of 
cytokine-driven human immunodeficiency virus type 1 replication by 
protease inhibitor. Journal of Infectious Diseases 176:1175-1179 (Nov 
1997).

(4) Andersson J, Fehniger TE, Patterson BK, Pottage J, Agnoli M, Jones 
P, Behbahani H, Landay L. Early reduction of immune activation in 
lymphoid tissue following highly active HIV therapy. AIDS 1998 
Jul 30;12:F123-F129.

(5) Markowitz M. Resistance, fitness, adherence, and potency: mapping 
the paths to virologic failure. JAMA 2000 Jan 12;283(2):250-1 

(5) Havlir DV, Hellmann NS, Petropoulos CJ, Whitcomb JM, Collier AC, 
Hirsch MS, Tebas P, Sommadossi JP, Richman DD. Drug susceptibility in 
HIV infection after viral rebound in patients receiving indinavir-
containing regimens. JAMA 2000 Jan 12;283(2):229-34 

======= 





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