Date: 09 May 1996 11:15:04
From: FRSHAW@delphi.com
Subject: NIH Herb Trial Fails

NIH-Funded HIV Herb Trial Reports Disease Progression
W. Fred Shaw, L.Ac., Dipl.Ac.

A six-month NIH-funded study has demonstrated that the popular 
herbal formulas used as the backbone of Traditional Chinese 
Medicine (TCM) HIV therapy are correlated with high viral 
replication and disease progression (1). At the same time, this 
study reported data that demonstrates the effectiveness of DNCB 
(dinitrochlorobenze), a cheap and non-toxic (2) treatment which 
activates cellular immunity, even in the presence of 
immunosuppressive and viral-replicating herbal therapy. The NIH 
study reported that persons using the standard herbal therapies 
for HIV disease (Composition-A in this case), on a daily basis 
for six months, experienced an almost 700% increase in their 
viral load. On the other hand, persons using the herbal 
therapy, in addition to weekly DNCB skin applications for six 
months, were reported to have a 50% decrease in their viral 
load. Viral load is the "gold standard" of laboratory markers 
for determining disease progression and the effectiveness of 
therapies for HIV disease.

While the study has been submitted for publication, the 
abstracts have already been published (3,4) and reported (5). 
The findings of the study appear to be accurate in terms of the 
reported virological and immunological data (CD4s, CD8s, viral 
burden and viral load). The CD4 and CD8 cell counts remained 
the same in both groups being studied during the six months, 
although important subset values of these lymphocytes were 
measured but not disclosed in the NIH report. Additionally, 
questions regarding the methodology and conclusions of this NIH 
study report appear to be in conflict with recent research (6-
11), and are presently under investigation by the NIH.

This study examined two groups of HIV-positive persons. One 
group was identified as the "control" arm, despite the fact 
that these individuals were using what has been termed the "ITM 
Wellness Protocol", a regimen of herbs and vitamins detailed in 
the study proposal (12). While the ITM Wellness Protocol 
includes vitamins and nutrients, it is primarily centered 
around the use of one herbal formula for all patients 
(Composition-A, 15 pills a day), in addition to another herbal 
formula based on the patient's own symptoms (such as Clear 
Heat, 9 pills a day). All 30 individuals studied -- the 12 in 
the "control" arm, as well as the 18 in the study group -- were 
taking at least 24 Chinese herbal pills per day, a strategy 
that employed up to 50 different herbs.

The group of 18 individuals designated as the "study" group 
used the ITM Wellness Protocol, together with DNCB applied to a 
two-by- two-inch patch of the skin on a weekly basis. This 
article refers to this group as the herb-loaded/DNCB group. The 
delayed-type hypersensitivity (DTH) rash that results from the 
application of DNCB to the skin is the Type IV allergic 
reaction (like poison ivy or oak) -- which is the only allergic 
response that provokes a cellular immune response. In this 
case, the weekly induction of the DNCB DTH healing response has 
been shown to activate cellular immunity (13-15), the branch of 
the immune system that is essential for the control of 
intracellular pathogens. Intracellular pathogens account for 
nearly all the opportunistic infections seen in AIDS, including 
the replication of HIV.

The NIH study proposal details an herb preloading period of 30 
days before the baseline (12). In other words, all patients in 
both study arms, including the "control" arm, ingested a 
minimum of 24 herbal pills every day for 30 days before the 
first blood and tissue specimens were taken. These first blood 
or tissue specimens were identified as the "baseline", or the 
beginning values, which would later be compared to the blood 
and tissue specimens taken after the six months of the study.

Although this study claims to have been randomized, the 
beginning (baseline) plasma viral loads of the patients 
indicate that the sicker patients were assigned to the herb-
loaded/DNCB group. In the herb-only group, the mean baseline 
value was 32,667 copies/mL, while the herb-loaded/DNCB group 
had a mean baseline value that was almost three times higher, 
at 89,625 copies/mL. Viremia in the range of 50,000 to 100,000 
copies/mL and higher is associated with HIV disease states and 
disease progression.

Viral load was determined through branched-chain DNA (bDNA) 
analysis. At six months, the herb-only group, which started 
with a mean baseline of 32,667 copies/mL, ended with a mean 
baseline of 207,000 copies/mL, an approximate seven-fold 
increase in viremia. The herb-loaded/DNCB group, which started 
with a mean baseline of 89,625 copies/mL, ended with a mean 
baseline of 42,331 copies/mL, more than a 50% decrease in 
viremia.

The two Principal Investigators for the study are associated 
with the Institute for Traditional Medicine (ITM) in Portland, 
Oregon (12). The manufacturer of the herbal formula central to 
this study (Composition-A) is Seven Forests, an ITM subsidiary. 
The fact that there was no DNCB-only control arm was central to 
a protest by ACT UP San Francisco at the July 1994 HIV/AIDS and 
Chinese Medicine Conference in San Francisco. At that time, ACT 
UP protested that this NIH-funded "DNCB study" was simply a 
camouflaged herb study - since it was being conducted by the 
manufacturer of the commercial herbal product that was central 
to the study. Interestingly, the study abstract contains NO 
reference to the use of herbs in this trial, and the 29-page 
NIH report only mentions the use of herbs in 3 brief comments.

Since 1994, this author has been reporting on the potential of 
herbs to contribute to HIV disease progression, especially when 
used for long periods of time (16-19). The leaders of the 
Traditional Chinese Medicine (TCM) community have not responded 
to these reports in a professional manner (20-22). Apart from 
state licensing boards, the TCM community lacks a professional 
peer-review process to evaluate therapies for safety. As a 
result, dangerous and life-threatening practices have emerged, 
such as that of herbal PCP "prophylaxis". In a New York herbal 
PCP study designed by a TCM practitioner, proven drug therapies 
were substituted with an unproven "natural" herbal PCP 
prophylaxis for patients at risk (23).

The herbal formulas that are advocated for lifetime use in HIV 
disease have never been shown to be safe in the treatment of 
this disease. It appears that these commonly used treatments 
have a significant potential for worsening disease progression. 
Studies of herbal formulas for HIV disease have been conducted 
by herb manufacturers since the late 1980's. However, these 
studies, one of which collected laboratory data (24), only 
report the positive subjective findings, and all of these 
studies remain unpublished.

This NIH-funded study demonstrates that these HIV formulas 
should be considered to be potential contributing factors for 
disease progression, since they are associated with viral 
replication and immune suppression. This finding is consistent 
with the immunological realities of HIV disease and the 
biomedical literature regarding the immune effects of these 
herbs (18). The popular herbal formulas include: Composition-A, 
Resist, Enhance, Essiac, Minor Bupleurum (SST) and others. 

The popular single-herb treatments should also be considered as 
contributing factors for disease progression, such as SPV-30, 
the Boxwood tree extract which contains steroidal alkaloids 
that have been compared to cyclosporine-A. Advertised as a 
"natural" form of AZT with secret ingredients (25,26), SPV-30 
has been shown to strongly suppress interleukin-2 and 
lymphoproliferative responses (25). While such suppressive 
treatments decrease viral replication through the suppression 
of cellular proliferation, it is not logical to expect, nor has 
it been proven, that an immune-suppressing treatment strategy 
would be helpful in a disease characterized by immune 
suppression. Certainly, suppressive therapies frequently offer 
the illusion of improvement, despite the increased potential 
for copathogen outbreaks. Nonetheless, patients often report 
the positive benefits identified with steroidal treatments: 
clearing of skin problems, increased appetite, weight gain, 
feeling better, more energy and many other subjective 
improvements. The "positive" increases in CD4 counts that are 
associated with steroidal treatments are also likely to be 
illusory, since cyclosporine-A has been shown to interfere with 
the apoptosis (programmed cell death) of activated CD4s (27), 
which simply increases the number of non-viable CD4s in 
circulation.

In conclusion, unless the immunological effect is known, the 
use of any herb or herbal formula for the treatment of symptoms 
in HIV disease should be considered a potential contributing 
factor for disease progression. 

References and Notes
(1) Cohen OJ, Pantaleo G, Loveless M, Fox CF, Orenstein J, 
Graziosi C, Vaccarezza M, Bradley B, Schwartzentruber D, 
Baird B, Fields L, Dharmananda S, Fauci A. April, 1996. 
Submitted for publication. "Immunotherapy of Human 
Immunodeficiency Virus infection with dinitrochlorobenzene 
does not ameliorate immunologic or virologic parameters of 
disease progression in peripheral blood or lymph nodes."
(2) Stricker RB, Goldberg B. Safety of topical 
dinitrochlorobenzene. [letter] Lancet 1995, Nov 11, 
346:1293.
(3) Cohen O and others. Effects of dinitrochlorobenzene therapy 
on viral load and cytokine expression in lymphoid tissue of 
HlV-infected individuals. Infectious Diseases Society of 
America 33rd Annual Meeting. San Francisco. September 16-18, 
1995. Abstract 475.
(4) Loveless M and others. Effect of dinitrochlorobenzene 
(DNCB) cutaneous sensitization on HIV disease progression. 
Infectious Diseases Society of America 33rd Annual Meeting. 
San Francisco. September 16-18, 1995. Abstract 471. 
(5) Bulletin of the Experimental Therapies for AIDS (BETA), San 
Francisco AIDS Foundation, March, 1996.
(6) Coventry BJ, Weeks SC, Heckford SE, Sykes PJ, Bradley J, 
Skinner JM. Lack of IL-2 cytokine expression despite IL-2 
messenger RNA transcription in tumor-infiltrating 
lymphocytes in primary human breast carcinoma. Selective 
expression of early activation markers. Journal of 
Immunology 1996, May 1, 156:3486-3492. NOTE: This 
information is of critical importance to the validity of the 
Th1/Th0/Th2 conclusions cited in the NIH herb study. This 
study challenges the assumption that cytokine protein 
expression always follows cytokine mRNA transcription.
 (7) Bour H, Peyron E, Gaucherand M, Garrigue J-L, Desvignes C, 
Kaiserlian D, Revillard J-P, Nicolas J-F. Major 
histocompatibility complex class I-restricted CD8+ T cells 
and class II-restricted CD4+ T cell, respectively, mediate 
and regulate contact sensitivity to dinitrofluorobenzene. 
European Journal of Immunology 1995, Nov, 25:3006-3010.
(8) Heufler C, Koch F, Stanzl U, Topar G, Wysocka m, Trinchieri 
G, Enk A, Steinman RM, Romani N, Schuler G. Interleukin-12 
is produced by dendritic cells and mediates T helper 1 
development as well as interferon-gamma production by T 
helper 1 cells. European Journal of Immunology 1996, Apr, 
26:659-668.
(9) Vyakarnam A; Matear PM; Martin SJ; Wagstaff M. Th1 cells 
specific for HIV-1 gag p24 are less efficient than Th0 cells 
in supporting HIV replication, and inhibit virus replication 
in Th0 cells. Immunology, 1995 Sep, V86 N1:85-96.
(10) Maggi E, Mazzetti M, Ravina A, Annunziato F, De Carli M, 
Piccinni MP, Manetti R, Carbonari M, Pesce AM, Del Prete G, 
Romagnani S. Ability of HIV to promote a Th1 to Th0 shift 
and to replicate preferentially in Th2 and Th0 cells. 
Science, 1994 Jul 8, 265(5169):244-248.
(11) Stanley SK, Ostrowski MA, Justement JS, Gantt K, Hedayati 
S, Mannix M, Roche K, Schwartzentruber DJ, Fox CH, Fauci AS. 
Effect of immunization with a common recall antigen on viral 
expression in patients with infected with human 
immunodeficiency virus type 1. New England Journal of 
Medicine 1996, May 9, 334:1222-1230. NOTE: Similar to the 
induction of Th2 responses by many of the herbs used to 
treat HIV disease, this study demonstrated that the antibody 
response -- not the Th1 response -- is associated with HIV 
viral replication and increased viral load.
(12) Loveless, M., Dharmananda, S., Fields, L., Bradley, B. NIH 
Proposal (Unpublished), "A prospective, randomized, blinded, 
comparative trial of the topical use of dinitrochlorobenzene 
(DNCB) in individuals infected with the human 
immunodeficiency virus (HIV)."
(13) Stricker RB, Goldberg B, Epstein WL. "Decrease in viral 
load associated with topical dinitrochlorobenzene (DNCB) 
therapy of HIV disease." Abstract Accepted for 1996 
Vancouver AIDS/HIV Conference.
(14) Traub A, Margulis SB. Use of dinitrochlorobenzene (DNCB) 
as an immune modulator in HIV-positive patients: a pilot 
study from Brazil. Blood 1995, Nov 15, 86(10)(S1):935a. 
[abstract 3728]. NOTE: "We conclude that topical DNCB 
therapy promotes clinical and immunologic improvement in 
HIV-infected patients. DNCB treatment should be especially 
useful in poorer countries with limited access in health 
care."
(15) Epstein WL, Stricker RB. Immunomodulation by allergic 
contact sensitization: the dinitrochlorobenzene story. 
American Journal of Contact Dermatitis 1995, Jun, 6(2):117-
121.
(16) Shaw, WF, Journal of the National Academy of Acupuncture 
and Oriental Medicine, "HIV Dementia in Medicine: Western 
and Eastern," Spring, 1995. 2(1)27:29. Also published in the 
California Acupuncture Association Bulletin, Nov/Dec, 1995. 
5.6;5:7.
(17) Shaw, WF, Holistic AIDS Response Program Bulletin, 
"Raising a Red Flag, How Safe are Herbal Medicines?", 
Feb/Mar 1996. X(1)1:3.
(18) Shaw WF, (submitted for publication), "Treating HIV 
Disease with Chinese Herbs: The Immunological Paradox," Feb. 
1996. NOTE: Also submitted to several of the NIH herb study 
authors (ref. 1), as well as the appropriate directors of 
the NIH, NIAID and FDA. This article details the 
immunological effects of the commonly-used Chinese herbs in 
terms of  HIV disease. This detailed review of the 
biomedical literature reveals how herbs can further suppress 
cellular immunity in HIV disease, while promoting Th0/Th2 
antibody responses that are associated with increased viral 
replication and disease progression.
(19) Shaw, WF, Bay Area Reporter. Letter. April 27, 1995. 8. 
NOTE: This letter was a warning to the HIV-positive 
community regarding the immunosuppressive effects of the 
popular herbal formulas for HIV disease, including Enhance, 
Composition-A, Resist and SPV-30. In response, the May 11, 
1995 issue of this weekly paper contained personal attacks 
from Misha Cohen, the Director of the Quan Yin Clinic, and 
David Stokes, the Study Coordinator for the SPV-30 informal 
trial. Cohen, the designer of Enhance, stated "as an outside 
observer, it appears that he (Shaw) has not read the 
protocol or researched the formulas." Further Cohen refers 
to the immunological herbal research as "biased and 
inflammatory" since it criticizes "many of the pearls of 
Chinese medicine in the treatment of HIV."
(20) Cohen, M. California Acupuncture Association Bulletin. 
Letter. May/June, 1995. 6.3;15:17. NOTE: In response to ref. 
16, the director of the San Francisco Quan Yin Clinic, Misha 
Cohen refers to the immunological herbal research as 
"inflammatory and derogatory," and offers unscientific 
research as evidence of herbal efficacy. Cohen has developed 
and promotes a "standard of care" designed around the 
Enhance herbal formulation. Instead of dealing with the 
issues of herbal immune suppression, Cohen prefers to attack 
advocates of other alternative therapies -- such as DNCB. 
The 1994 income tax return for Dr. Cohen's non-profit HIV 
clinic (Quan Yin Clinic, San Francisco), reveals nearly 
$100,000 is herbal sales, almost one-third of the clinic's 
reported income.
(21) Surasky A, Dierauf B, Kulkowitz S, Barlay B, Bernstein M, 
Sailer E, Mosca C, Fishler J, Levesque M, Stapleton K, Lowe 
S. Holistic AIDS Response Program Bulletin. "San Francisco 
Acupuncturists take issue with ACT UP San Francisco." Dec 
1995/Jan 1996. IX(6) 1:2. NOTE: All the authors are licensed 
acupuncturists of the Quan Yin Clinic of San Francisco. In 
this letter, the authors refer to anecdotal improvements in 
HIV patients using herbal therapies but offer no objective 
or scientific evidence of clinical improvement or increased 
survival. These authors state "the ability of western 
scientific methods to measure and assess the efficacy of TCM 
is limited." Again, these TCM practitioners irrationally 
detract from the discussion of herbal immune suppression by 
attacking other alternative therapies -- such as the use of 
DNCB.
(22) Health Concerns. The Meridian Times. Fall/Winter 1995-6. 
9. NOTE: Health Concerns is the manufacturer of Enhance, one 
of the popular herbal formulas discussed here. In response 
to a letter warning about PCP herbal prophylaxis in the same 
issue, the unknown Health Concerns author(s) defend herbal 
therapies by attacking other alternative therapies -- such 
as DNCB. Again, the author(s) recite only the anecdotal 
reports of symptomatic improvement in unpublished herbal 
studies.
(23) Paul, S. Immune Enhancement Project Bulletin. "Update on 
the use of Qing Hao as prophylaxis for PCP." Summer, 1995. 
7. NOTE: Only anecdotal reports of benefit have been 
reported in this study, in which patients on PCP herbal 
prophylaxis were also using Enhance. 
(24) Health Concerns, California Acupuncture Association 
Bulletin, "Preliminary results from Enhance/HIV study." Jan. 
1994. 15. NOTE: This randomized, controlled, double-blind 12 
week study conducted under the auspices of San Francisco 
General was never published. This "preliminary" report only 
reported anecdotal benefits from the trial, including 
improvement in "life satisfaction". The principal 
investigators were Misha Cohen, OMD, L.Ac. and Jeff Burack, 
M.D. of San Francisco General.
(25) Vandermander J. Internet posting on sci.med.aids board. 
May 26, 1995. NOTE: Vandermander is the Scientific Director 
of Arkopharma, the manufacturer of SPV-30, who reported on 
the immunological effects of SPV-30 in response to internet 
warnings to HIV patients regarding the immunosuppressive 
steroidal alkaloids of Boxwood. In this communication, 
Vandermander disclosed the immunosuppressive properties of 
SPV-30 and advised that SPV-30 consisted of secret 
ingredients by stating "SPV-30 IS NOT simple boxwood."
(26) SPV-30 Advertisements. POZ Magazine. Fall, 1995. 
Advertising inserts: "SPV-30 Study: A One Man Crusade" and 
"SPV-30 Fact Sheet". NOTE: SPV-30 advertisements, news 
articles and literature often refer to the Technical Advisor 
of the SPV-30 trial as "Dr." Beth Mestman. Dr. Mestman is 
NOT a medical doctor, but rather is a New York-licensed 
Chiropractor. The New York Board of Professional Discipline 
advises that it is illegal for a Chiropractor to use the 
title "Doctor" without the qualifying  initials "D.C." 
(Doctor of Chiropractic) following their name. 
(27) Groux H; Torpier G; Monte D; Mouton Y; Capron A; Ameisen 
JC. Activation-induced death by apoptosis in CD4+ T cells 
from human immunodeficiency virus-infected asymptomatic 
individuals. Journal of Experimental Medicine, 1992 Feb 1, 
175(2):331-40.