
AIDS TREATMENT NEWS Issue #242, March 1, 1996
   phone 800/TREAT-1-2, or 415/255-0588

CONTENTS:

Curcumin: Clinical Trial Finds No Antiviral Effect

Protease Inhibitor Approvals -- Will People Be Cut Off Drug? 
Followup Studies Proposal Needs Support

Rolipram: Antidepressant Used in Europe and Japan Might Have 
Promise Against TNF, HIV

Study Finds AIDS Patients Live Longer When Their Doctors Have 
More Experience Treating  HIV

Protease Inhibitors at Retroviruses Conference: Agouron's 
Results

Retroviruses Conference: Obtaining Copies of Abstracts


DHEA: Threat to Access?


***** Curcumin: Clinical Trial Finds No Antiviral Effect

by John S. James

A clinical trial with 40 volunteers, reported at the 3rd 
Conference on Retroviruses and Opportunistic Infections, 
found that curcumin, a popular "alternative" treatment for 
HIV, had no effect in reducing viral load or in increasing 
CD4 counts.(1) This trial was conducted by the CRI (Community 
Research Initiative) of New England, a community-based 
research organization.

Curcumin is an ingredient of turmeric, a spice used in making 
curry; it is the substance which gives curry its yellow 
color. Laboratory tests had shown that curcumin has 
substantial anti-HIV activity in cell cultures, at 
concentrations not damaging to the cells.(2) A 1994 clinical 
trial of curcumin by AIDS Research Alliance (named SEARCH 
Alliance at that time) was inconclusive, largely because of 
great unexplained variability in the viral load results. [For 
historical background on curcumin and HIV, see AIDS TREATMENT 
NEWS # 174 (May 7, 1993), #176 (June 4, 1993), and #198 (May 
6, 1994). Our report on the AIDS Research Alliance trial is 
in issue #198.]

Of the 40 persons entered into the recent trial by the CRI of 
New England, two dropped out due to adverse events unrelated 
to the curcumin study. Of the other 38, 23 were randomized to 
a high-dose group and 15 to a low-dose group. (This study 
used the popular "Turmeric Power" brand of curcumin; the high 
dose was four capsules four times a day, and the low dose was 
3 capsules three times a day.) Each group was further 
randomized to begin curcumin either immediately or after 8 
weeks; both groups received the treatment for eight weeks. 
Both groups had at least two viral load tests to establish 
the baseline viral load value (those in the delayed-treatment 
group had three tests for their baseline); viral load tests 
were also given at 4 weeks and at 8 weeks of treatment.

The following viral load averages were published in the 
abstract of this study presented at the Retroviruses 
conference. In the high-dose group, the average viral load 
was 4.569 logs (37,100 copies) at baseline, 4.226 logs 
(16,800 copies) at four weeks, and 4.568 logs (37,000 copies) 
at eight weeks. In the low-dose group, the corresponding 
figures were: baseline 4.989 logs (97,500 copies), four weeks 
4.623 logs (42,000 copies), and eight weeks (4.822 logs, 
66,400 copies). On the surface, this looked to us like a 
statistically significant result; but we contacted the 
researchers and found that the apparent viral load drop, in 
both the high-dose and low-dose groups, was caused in each 
case by a single individual with a single value which was 
wildly out of range (in one case, more than 100 times any 
other viral load result from that person); the extreme values 
were probably due to a laboratory error. When these anomalous 
values were excluded, no effect on viral load was found.

 CD4 cells showed a slight rise in the high-dose group 
(baseline average 231, four weeks 247, eight weeks 262), and 
a consistent fall in the low-dose group (baseline 244, four 
weeks 223, eight weeks 146). But neither result was 
statistically significant, meaning that these changes were 
likely due to chance and cannot be taken as evidence of any 
treatment effect.

Researcher Jim Hellinger, M.D., of the Community Research 
Initiative of New England, noted in a private communication 
to us that, "Despite the lack of apparent antiviral or CD4 
effects, most participants liked taking curcumin, and felt 
better taking it, and put up with the minor GI effects. We 
did not plan any formal analysis of these effects, but there 
certainly are other ways in which curcumin might be 
active..." A blood test for curcumin levels, now being 
developed for a different study, may provide more information 
about why no antiviral activity was found.

Comment

In 1993 we became interested in curcumin because of its 
scientific rationale, and the laboratory findings of anti-HIV 
activity -- plus the fact that the potential treatment was 
safe, inexpensive, and widely available. We also heard a few 
early anecdotal reports of viral load reductions in patients 
who tried curcumin.

One of the biggest problems in AIDS treatment development is 
that only proprietary drugs tend to get tested -- assuring 
that any resulting treatment will be very expensive, and also 
that testing will take a long time, since proprietary 
substances tend to be new chemicals, not familiar drugs, 
herbs, or food components already in wide human use. There is 
a critical need for social organization to screen promising 
leads which for commercial reasons are not being pursued by 
pharmaceutical companies. Both the CRI of New England, and 
the AIDS Research Alliance, are to be commended for their 
studies of curcumin. Now that viral load testing is becoming 
more available, and the technology more reliable, small 
trials to screen for antiviral activity in people are 
becoming much easier and more feasible than they were in the 
past.

We must realize that the large majority of potential 
treatments which have the scientific rationale and/or 
laboratory or anecdotal information to justify a small trial 
will turn out not to be useful. But there are many promising 
leads among substances already available and in human use; 
the odds are good that at least a few of them will prove 
helpful. A single one that does will justify all the effort 
and expense of testing the others.

References

1. Hellinger JA, Cohen CJ, Dugan ME, Day JM, Cavanaugh JF, 
and Glidden D. Phase I/II randomized, open-label study of 
oral curcumin safety, and antiviral effects on HIV-RT PCR in 
HIV+ individuals. 3rd Conference on Retroviruses and 
Opportunistic Infections, January 28 - February 1, 1996, 
Washington DC [abstract #140].

2. Li CJ, Zhang LJ, Dezube BJ, Crumpacker CS, and Pardee AB. 
Three inhibitors of type 1 human immunodeficiency virus long 
terminal repeat-directed gene expression and virus 
replication. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, 
USA, March 1993; volume 90, pages 1839-1842.


***** Protease Inhibitor Approvals: Will People Be Cut Off 
Drug? Followup Studies Proposal Needs Support

by John S. James

The PWA Health Group, the largest AIDS buyers' club in New 
York, is circulating a sign-on consensus letter asking the 
FDA, when it approves Merck's Crixivan(R) (indinavir) and 
Abbott's Norvir(TM) (ritonavir), to require the companies to 
obtain long-term followup data, by allowing people currently 
receiving the drugs (in clinical trials, or in the expanded-
access lottery programs) to continue their treatment in long-
term followup studies.

This proposal addresses two problems. For those now receiving 
either of these experimental treatments, it would prevent 
involuntary interruption of therapy if they cannot pay for 
the drugs when they go on sale. Interruption of therapy might 
be especially problematic with these drugs, because of 
concern that it might help a person's virus become resistant 
to most or all protease inhibitors, greatly reducing the 
value of this class of drugs for that person.

The other problem -- lack of long-term data -- concerns 
everybody who uses these drugs. It is widely expected that 
one or both of them will be approved soon -- as almost 
everyone wants -- perhaps in the next several weeks. Then 
thousands are likely to start using them.

But very few people have taken these drugs for more than a 
year. The fastest way to get the needed long-term data now is 
to allow those who have already been using the drugs to 
continue, with monitoring in a followup study. Then, in case 
some long-term safety problem develops after two or three 
years of use, the many thousands of people who started the 
drug when it was approved would have advance warning, and 
could probably avoid the problem by interrupting or changing 
therapy if necessary. But there is widespread concern that 
unless the FDA requires these studies, the companies will 
stop providing free drug once they can sell it instead, and 
the studies will not be done.

You can help by signing the consensus letter, and if 
relevant, getting your organization to do so. To sign on, or 
for more information, including a copy of the statement, 
contact Sally Cooper at the PWA Health Group, 212/255-0520 or 
fax 212/255-2080.


***** Rolipram: Antidepressant Used in Europe and Japan Might 
Have Promise Against TNF, HIV

by Denny Smith

An antidepressant drug known as rolipram has been found to be 
a potent inhibitor of tumor necrosis factor, which means it 
might be a useful treatment for HIV infection. Unfortunately, 
the drug may not reach clinical trials because the companies 
that control rights to it are not inclined to support further 
development.

This situation came about last year, when researchers 
supported by the U.S. National Institute of Allergy and 
Infectious Disease and led by Paul Skolnik, M.D., at Tufts 
University and the New England Medical Center, discovered 
that in laboratory tests rolipram strongly inhibited tumor 
necrosis factor (TNF), a naturally occurring chemical 
messenger that the immune system produces to excess in some 
diseases, including HIV infection. The work was published 
last October in the journal AIDS.(1)

Many of the symptoms of AIDS that are not caused by an 
opportunistic illness are at least partly the result of too 
much TNF: fatigue, fevers, dementia, aphthous ulcers, and, 
the most threatening, wasting. In fact, TNF is sometimes 
called cachectin, referring to its cachexia-related, or lean 
muscle destroying, effects. Many researchers now believe 
there is an HIV/TNF feedback loop in which TNF enhances HIV 
replication while HIV progression increases TNF production.

TNF inhibitors would theoretically interrupt that cycle, and 
several of them have received attention recently in both 
laboratory research and community practice. NAC, 
pentoxifylline and thalidomide in particular have been widely 
discussed in medical reports, including AIDS TREATMENT NEWS. 
But only thalidomide has been reported to be clinically 
valuable. It effectively controls aphthous ulcers and may 
reverse the loss of lean muscle mass.

 At best, however, thalidomide is a problematic drug. It 
causes sedation, which is why it was developed in the first 
place. But it can also provoke a serious sulfa-like reaction 
in many people with HIV, and it can cause neuropathy and 
neutropenia with extended use.  And, of course, it leads to 
terrible birth defects if taken during pregnancy, which is 
why it was never licensed in the U.S.

A newer, ostensibly less toxic, generation of TNF inhibitors 
is under development by Celgene, one of the makers of 
thalidomide. But animal and human trials of those drugs could 
take years to complete. Rolipram is available and used now in 
Japan; it has also been used extensively in Europe.

In his research, Dr. Skolnik found that rolipram was at least 
10 and perhaps 600 times more powerful then pentoxifylline at 
inhibiting tumor necrosis factor. Both drugs are 
phosphodiesterase inhibitors, although rolipram is more 
specific in that regard. Rolipram is also known to cross the 
blood-brain barrier, which is an important criterion for any 
HIV treatment. It is considered an essentially safe drug, the 
main side effect being mild gastrointestinal distress at 
doses approaching 15 mg a day. The dose prescribed for 
antidepressant use ranges between 0.5 to 1 mg taken three 
times daily.

Some of the data published by Dr. Skolnik's team seems to 
suggest that the amount of the drug necessary to inhibit TNF 
might not be tolerable in practice. The peak plasma 
concentration of rolipram from a single human dose -- 1 mg, 
when the drug is used as an antidepressant -- is 0.12 
micromolar. But in the laboratory tests, the concentration 
required for 50% inhibition of HIV was 10 to 60 micromolar -- 
more than 80 times what is achieved in plasma by normal use 
of the drug.

In this case, however, the laboratory concentration needed to 
inhibit TNF may not predict what happens in people. In the 
body, if rolipram reduces excessive levels of TNF, as it is 
supposed to do, that reduction should prevent the excess TNF 
from stimulating HIV replication. Some residual TNF activity 
may be desirable for normal immune function. 

In the laboratory, rolipram is acting on a largely static 
situation; but in the body, TNF and HIV interact in a 
constantly changing dynamic in specific locations. Local 
concentrations of TNF and rolipram may not be paralleled by 
plasma levels.

Even if the highest tolerated dose of rolipram does not 
inhibit HIV, inhibiting any amount of excess TNF could be 
useful for preventing wasting, fatigue, dementia and aphthous 
ulcers. So while the laboratory data may raise doubts, they 
do not reduce the need for clinical studies to see if this 
drug could have a role in the treatment of HIV disease. Only 
clinical trials with HIV-infected participants can determine 
if a dose that is tolerable will also produce clinical 
improvement.

Rolipram was first developed as an antidepressant and 
marketed in Europe by Schering AG. It is also being 
investigated as possible treatment for multiple sclerosis. 
The development rights to rolipram in the U.S. and Japan were 
licensed to Berlex Laboratories and Meiji Seika Kaisha, 
respectively. Since rolipram does not inhibit HIV directly, 
as do drugs which inhibit reverse transcriptase (AZT, ddI, 
ddC, d4T, 3TC) or protease (saquinavir, indinavir, 
ritonavir), it would probably not become an enormously 
profitable first-line treatment for primary HIV infection 
even if the research proceeds. That is why, after all, any 
number of potential treatments are not pursued.

But, for reasons discussed above, TNF inhibitors could easily 
become indispensable supportive therapies, much as acyclovir 
and testosterone are now. Rolipram or similar drugs could 
possibly improve the quality of life and even the survival of 
many people with AIDS.

Even before his research was published, Dr. Skolnik proposed 
a pilot trial of the drug in HIV-infected patients, and asked 
Schering for support. For months, the request passed back and 
forth between Schering, Meiji and Berlex, and responsibility 
for further development of the drug remained unclear. 
Finally, it became known that Schering had submitted an 
Investigational New Drug application to the FDA some years 
ago (presumably for a non-HIV related indication), and does 
not now want to pursue the research necessary to bring the 
IND up to date.

Admittedly, such research could be an expensive commitment. 
But for a promising agent to be withheld for non-scientific 
reasons from a legitimate research effort seems distastefully 
reminiscent of the 1980s. AIDS activists were successful in 
reversing some similar decisions, but only after unfortunate 
public confrontations.

An alternative may be for the drug to be imported and carried 
at HIV buyers' clubs, depending on how much community support 
rolipram gathers. Readers who have knowledge of, or 
experience with, rolipram, are encouraged to contact Denny 
Smith or John S. James at AIDS TREATMENT NEWS, fax 415/255-
4659, phone 415/255-0588.

Rolipram in Medical Literature

Extensive computer searches failed to find any mention of 
rolipram in relation to HIV or AIDS, except for the paper by 
Dr. Skolnik's group. And that paper was omitted from 
AIDSLINE, apparently in error -- which may have reduced the 
attention this work received.

We found 475 citations mentioning rolipram in MEDLINE, the 
general medicine database of the U.S. National Library of 
Medicine -- and 739 references in EMBASE, a European database 
which often has more citations than MEDLINE on new or 
experimental treatments. Most of the recently published work 
consists of highly technical investigations into the drug's 
mechanism of action.

References

1. Angel JB, Saget BM, Walsh SP, and others. Rolipram, a 
specific type IV phosphodiesterase inhibitor, is a potent 
inhibitor of HIV-1 replication. AIDS. 1995; volume 9, pages 
1137-1144.


***** Study Finds AIDS Patients Live Longer When Their 
Doctors Have More Experience Treating  HIV

by John S. James

A study of 403 adult men diagnosed with AIDS from 1984 
through 1994 within an HMO found large differences in 
survival depending on physicians' experience (measured in 
large part by how many AIDS patients they had cared for).(1)

"After AIDS diagnosis, median survival among patients of 
physicians with the least AIDS experience was 14 months, 
versus 26 months among patients of physicians with the most 
experience (P<0.001). After controlling for severity of 
illness and year of AIDS diagnosis, patients cared for by 
physicians with the most experience had a 31 percent lower 
risk of death compared to patients cared for by physicians 
with the least experience (P<0.02). The adjusted relative 
risk was 44 percent lower for patients of the most 
experienced physicians (P<0.02) among 244 patients diagnosed 
from 1989-1994, controlling for CD4 cell count and severity 
of illness."

Other data suggested that the difference may have been 
largely due to better use of PCP prophylaxis, including 
better monitoring to know when prophylaxis should begin. 
"Among 212 patients with CD4 cell counts of <200 mm3 prior to 
AIDS diagnosis, patients of physicians with greater 
experience had a significant increase in CD4 cell count 
monitoring (P<0.001), prophylaxis against Pneumocystis 
carinii pneumonia (PCP) (P<0.001), and a decrease in the 
proportion of patients diagnosed with PCP as their AIDS-
defining illness (P=0.10)."

[Note: As this issue went to press, we learned that a full 
report of this research is due to be published in a couple 
weeks.]

Comment

This result should reinforce the importance of people finding 
out if they have HIV, and getting medical care if they do. No 
treatment at all -- including no PCP prophylaxis no matter 
how much it is needed -- is worse than treatment by the least 
experienced physicians. In the U.S. and some other countries, 
PCP prophylaxis is clearly the most important AIDS-related 
treatment in reducing the risk of death. And it is 
inexpensive, so there is seldom any economic obstacle to 
receiving it.

Also, this result suggests that HIV care does need to be a 
specialty among physicians, instead of being left to general 
practitioners. Inexperienced AIDS physicians should be 
working under supervision so that their patients can be 
assured of adequate care.

This finding also emphasizes the importance of the 
development of accepted guidelines and standards of care for 
HIV treatment. Today the situation is chaotic, with vast 
differences among physicians, and many patients receiving 
inadequate care.

References

1. Kitahata MM, Koepsell TD, Deyo RA, Maxwell CL, Dodge WT, 
and Wagner EH. Physician Experience and Survival Among 
Patients with AIDS. 3rd Conference on Retroviruses and 
Opportunistic Infections, January 28 - February 1, 1996, 
Washington DC [abstract #413].


***** Protease Inhibitors at Retroviruses Conference: 
Agouron's Results

by John S. James

The protease inhibitors now furthest along in human use or 
testing are saquinavir (Invirase(TM), by Hoffmann-La Roche -- 
the only protease inhibitor now approved), indinavir 
(Crixivan(R), by Merck), ritonavir (Norvir(TM), by Abbott), 
and nelfinavir (Viracept(TM), by Agouron -- the drug was 
formerly called AG1343). AIDS TREATMENT NEWS already examined 
the Abbott (issue #240) and Merck (issue #241) protease 
inhibitor results presented at the Retroviruses conference. 
(Little clinical information on saquinavir was presented 
there -- only one abstract, #155, on reduced viral 
sensitivity during treatment -- probably because Roche had 
already presented the available information during the FDA 
approval process.)

Agouron protease inhibitor is at an earlier stage of 
development than the other three; about 120 patients have 
taken nelfinavir in studies so far.

Agouron's latest clinical trial data on nelfinavir became 
available too late for regular submission to the Retroviruses 
conference, and was turned down for the Late Breaker session, 
which had room for less than a third of the abstracts 
submitted to it -- and established various selection rules 
under which Agouron's abstracts did not qualify. (An earlier 
study of nelfinavir was accepted at the Retroviruses 
conference.(1) Agouron provided some of the results of its 
recent trials to the press, and at a community meeting on 
January 31.

One recent small trial found an average maximum reduction of 
HIV viral load from nelfinavir alone of about 98% at the best 
doses, after four weeks. Everyone's CD4 count increased.

Also, Agouron reported that an ongoing trial of the 
combination of nelfinavir plus d4T has found a greater than 
99% average reduction in viral load. In a majority of the 
volunteers using this combination, the viral load was reduced 
to below the limit of detection (about 500 copies per 
milliliter, with the assay which was used). In comparison, 
d4T alone reduced viral load by about 75% in this trial.

Agouron states that nelfinavir has shown an excellent safety 
profile, with only one of about 120 volunteers having stopped 
the drug due to adverse effects which possibly were drug 
related. The most common side effect is loose stools or 
diarrhea.

Larger trials of nelfinavir are now recruiting at more than 
40 sites in over 30 U.S. cities. For more information, see 
the announcement in AIDS TREATMENT NEWS #240 (February 9, 
1996), or call Agouron's information line, 800/501-2474.

References

1. Webber S, Shetty B, Wu E, and Zorbas M. In vitro and in 
vivo metabolism and cytochrome p450 induction studies with 
the HIV-1 protease inhibitor, VIRACEPT(TM) (AG1343). 3rd 
Conference on Retroviruses and Opportunistic Infections, 
January 28 - February 1, 1996, Washington DC [abstract #144].


***** Retroviruses Conference: Obtaining Abstracts

There are at least three ways to obtain copies of the 
published abstracts of the Conference on Retroviruses and 
Human Infections:

* Abstract books are still available for $25 from the 
Infectious Diseases Society of America. For more information, 
call 703/299-0200.

* The abstracts are also available at no cost through the 
World Wide Web, at http://www.idsociety.org. You can quickly 
search all the abstracts for author, or for any word used.

* The abstracts will also be available online through 
AIDSLINE, although they are not there yet as this newsletter 
goes to press. AIDSLINE is produced by the U.S. National 
Library of Medicine; accounts are available free to 
organizations and individuals.

Some AIDS service organizations provide libraries where the 
public can obtain such information in print or by computer.


***** DHEA: Threat to Access?

by Tim Kingston

[Note: For background on DHEA, see the article and the 
interview in AIDS TREATMENT NEWS #239, January 19, 1996. DHEA 
has *not* been found to reduce viral load or increase CD4 
count in persons with HIV, but it might improve quality of 
life for some people, or have other uses. This report 
investigates the possibility that it could be made illegal in 
the U.S., on the grounds that it might be abused by athletes 
-- even though there does not appear to be even a single 
reported case of such abuse, and no one knows if DHEA would 
have any effect on muscle building at all.

Our recent coverage of DHEA began when we asked reporter Tim 
Kingston to investigate the persistent rumors and fears that 
DHEA was about to be banned. Our coverage in issue #239 began 
as an effort to write an introduction to this article. JSJ]

For years DHEA has been one of the most popular potential 
treatments sold by the HIV buyers' clubs. Today there is a 
danger that it might be largely banned in the United States. 
This would happen by having DHEA declared a "schedule III" 
controlled substance, on the grounds that it might be abused 
by athletes to build muscle, like an anabolic steroid. 
Controlled substances can only be prescribed for certain 
uses; and since DHEA has no FDA-approved use, it might become 
unavailable both for clinical practice and for community-
based research. There are no significant safety concerns; the 
most likely reason for a ban would be that the treatment is 
becoming too popular outside of the HIV community, where it 
is being promoted for possible life-extension and "smart 
drug" benefits in middle aged and elderly individuals.

How serious is the current danger that access to DHEA may be 
cut off? The short answer is that it is impossible to know. 
For years there have been rumors that DHEA was to be banned 
as a controlled substance. That has not happened yet. But 
when we investigated the rumors, we learned that different 
enforcement agencies have very different views -- and the 
outcome could go either way. Some sectors of the FDA (Food 
and Drug Administration) seem perfectly happy to define DHEA 
as a food supplement; others insist that it is a drug and 
therefore subject to FDA drug regulation. And many at the DEA 
(Drug Enforcement Agency) regard DHEA as an anabolic steroid, 
subject to abuse by body builders, and therefore subject to 
stringent government regulation.

DHEA advocates are particularly worried about new government 
regulation because of an attempt by the New Jersey state 
prosecutor's office to press charges against a 75 year old 
man this summer who was using the substance to retard the 
effects of aging. The charges were dropped, but concern 
remains high about federal action against DHEA, especially 
among individuals and groups who advocate DHEA as an anti-
aging treatment. There is also concern at the Healing 
Alternatives Foundation in San Francisco, and the PWA Health 
Group in New York, major HIV buyers' clubs that carry DHEA.

Steven Fowkes, director of the Cognitive Enhancement Research 
Institute, a smart-drug research group in Menlo Park, 
California, asserts that the FDA may be trying to figure out 
a way to go after DHEA ever since the Dietary Supplement 
Health and Education Act (DSH&EA) of 1994, defined dietary 
supplements as foods and thereby prevented the Agency from 
treating DHEA as a drug without the required hearings. Fowkes 
says he has a "deep throat" source at the DEA who charges 
that the FDA has been pushing the DEA to reschedule DHEA as a 
schedule III drug. 

Fowkes says under the DSH&EA, the FDA would have to hold 
hearings to get DHEA officially classed as a drug and subject 
to FDA regulation; but that the DEA could define it as a 
Schedule III substance without a hearing. "If the FDA can 
pressure the DEA to schedule DHEA as an anabolic, then they 
are freed of the restraints imposed upon them by the DSH&EA. 
By getting somebody else to do their dirty work, the FDA can 
do an end run around the DSH&EA."

FDA sources flatly deny that their agency has applied any 
pressure on the DEA to redefine DHEA. FDA spokeswoman Janet 
McDonald tartly noted, "We don't define things. It is either 
regulated or not regulated. It is either approved or not 
approved. DHEA is not an approved substance." 

One FDA source acknowledges that the agency did instruct 
manufacturers of DHEA to discontinue selling the substance in 
April 1985 [for weight loss] because it had not been reviewed 
for safety and efficacy. FDA sources also contend that DHEA 
was considered a drug by the FDA because it was "intended or 
advertised to affect the body's normal functioning."

Meanwhile, over at the DEA, Howard McClain, chief of the 
agency's drug and chemical evaluation section in Washington 
D.C., says he is not aware of any request for rescheduling 
from the FDA, but acknowledges "it is possible they asked 
someone in the DEA" given that the agency is a huge 
"worldwide" agency. He asserts that DHEA is under review 
because it is in the scientific literature and not because of 
any special interest in the substance by the DEA.

McClain does note that DHEA is now under review by the DEA to 
see if it can be classed as an anabolic steroid subject to 
schedule III regulation. "Chemically [DHEA] is very similar 
to testosterone, but we have not been able to determine if it 
produces muscle growth," says McClain. "If we determine that 
it [does]... then it would be an anabolic steroid and would 
then be schedule III by definition."

While DHEA is not listed as a regulatable anabolic steroid, 
it could fall under a catch-all phrase that allows DEA action 
in the case of substances that act like testosterone. [DEA 
drug scheduling is based on potential for abuse, with heroin 
as a schedule I drug and cough syrup with codeine as a 
schedule IV drug.] But McClain says, "We don't have any 
evidence of illicit activity."

Federal Confusion

Although federal agencies in Washington D.C. appear to have 
reached a sort of consensus--after some prodding--that DHEA 
is a drug, but one not yet subject to DEA action or FDA 
regulation, that message has not yet meandered down the chain 
of command. Interviews with FDA and DEA offices in San 
Francisco and Texas indicate that not only does the Federal 
Government not know how to define DHEA, its various agencies 
at various levels cannot agree on a single position about the 
substance. 

When AIDS TREATMENT NEWS first contacted FDA sources in 
Washington, DHEA was initially described as a food 
supplement. As one friendly FDA source put it, "Nobody really 
knows what to call it; the only thing I had got was that it 
was pretty definite that we don't consider it a schedule III, 
and that leaves [DHEA] in the realm of dietary supplements. 
If the agency considered it a drug they would go in and say 
you can't sell this stuff as a dietary supplement."

Yet after a few more calls from AIDS TREATMENT NEWS and 
further research on FDA's part, DHEA was in fact held to be a 
drug by the agency. But in California, Dr. Wallace Winters, 
the Pacific region medical officer, said right from the start 
that DHEA is "basically an anabolic [steroid]; the game is to 
sell it as a dietary supplement." Winters says that because 
of the DSH&EA "the FDA has backed off on a lot of stuff... at 
the present time [DHEA] is in limbo."

Inconsistencies within a single agency are also striking at 
the DEA. Where Howard McClain at DEA headquarters in 
Washington D.C. says that DHEA is under review for inclusion 
in the agency's list of schedule III drugs, DEA offices in 
San Francisco and Houston have already come to their own 
diametrically different conclusions about the substance. 

In San Francisco one DEA agent initially thought DHEA 
"sounds" like a controlled substance, but on further review 
found it was not on the DEA list. Further inquiries were 
referred to DEA headquarters. But in Texas another DEA 
officer came to the exactly opposite conclusion, saying 
determinedly that DHEA is indeed a schedule III anabolic 
steroid. That same agent also stressed that she was unaware 
of any enforcement action undertaken by the DEA against DHEA. 

The same inconsistency was also evident in comparisons 
between agencies within those states. In California an 
official with the State Food and Drug Branch asserts that 
DHEA is not classified as a drug, but as a chemical. In Texas 
the Texas Department of Public Health equally vehemently 
declared that DHEA is soon to be declared a controlled 
substance. Lydia Gonzales of the Texas Department of Public 
Health says that she was told that DHEA would be declared a 
schedule III controlled substances as long ago as summer 
1995.

New Jersey Prosecution

Nowhere has the government's confusion about DHEA been more 
evident than in Bergen County, New Jersey. On August 21 1995 
Mr. Paul Gallo, a 75 year old school teacher, went to pick up 
a shipment of DHEA he had ordered from Germany. He was met by 
a county narcotics strike force, and arrested and charged 
"for the dubious crime of importing DHEA," says Gallo's 
attorney Ralph Fucetola. 

Even though charges were dismissed, the Gallo case is of 
particular concern to DHEA advocates, because they are 
worried that it may be a way for the federal government to 
set up a legal precedent to prosecute DHEA distributors. They 
fear that if state agencies go after DHEA, that could be used 
as legal precedent for federal action.

According to Fucetola, the New Jersey postal authorities had 
issued an erroneous import alert on DHEA in June 1995. When 
Mr. Gallo's package arrived, the post office contacted the 
state prosecutors office, and the arrest was organized. Gallo 
was arrested and intimidated into giving up the rest of the 
DHEA he had. At that point Fucetola was contacted by the Life 
Extension Foundation, a Florida based rejuvenation group that 
has tangled with the FDA in the past.

Fucetola conducted a search of the federal register and found 
no mention of DHEA either as an illegal substance or as an 
anabolic steroid. Fucetola sent Fred Swhanweed, the Bergen 
County prosecutor, a letter pointing out there were no legal 
precedents for prosecution and no evidence available that 
DHEA was an anabolic steroid. Fucetola also obtained letters 
from a number of DHEA experts decrying the arrest. Shortly 
thereafter all charges against Gallo were dropped. The DHEA 
was given back to him on January 17.

But Swhanweed says the fact that the charges were dropped has 
nothing to do with the fact that DHEA is not classed as a 
schedule III drug. Instead, he insists he was told by the 
state police lab that DHEA is a schedule III drug. He says 
the charges were only dropped out of compassion for a 75 year 
old man who did not know that what he was doing was illegal. 
Swhanweed insisted testily, "The controversy about whether it 
should or should not be a controlled substance, that did not 
enter into the decision to dismiss the case."

Other sources suggested that the New Jersey State Police 
crime lab had made an erroneous determination that DHEA was 
illegal when it was not, perhaps based on the catch-all 
phrase in the DEA drug scheduling registry allowing for DEA 
action against drugs that are like anabolic steroids. Charles 
Tindall, chief forensic scientist for the New Jersey State 
Police, acknowledged that DHEA is "not on the books," but he 
declined to make any further comment on what happened in the 
Gallo case. Tindall did say that he was in the middle of 
writing a report that he would be forwarding to the New 
Jersey Attorney General's office about the Gallo case.

Ralph Fucetola was less circumspect about what he thought 
happened in Bergen County. "What is going on is bureaucratic 
incompetence. There was a post office alert based on 
erroneous information, [and because] the drug war is so 
great, little niceties like actually scheduling something and 
reporting it don't matter. [Thus] we have the narcotics 
squads raiding 75 year old men over vitamins."

The Future

Professor William Regelson, a professor of medicine and 
microbiology at the Medical College of Virginia and a noted 
expert on DHEA, describes DHEA as a native hormone that was 
for many years regarded as a "junk steroid" despite the fact 
it is one of the most plentiful in the human body. Now, 
Regelson says DHEA has shown promise in the treatment of 
lupus and other autoimmune diseases; it balances the immune 
responses that lupus disequilibrates. He adds that DHEA also 
blocks the type 2 herpes virus and has possibilities in 
treating several other conditions. Regelson asserts DHEA 
"enhances resistance to infection and restores immunity in 
mice and apparently in older people, and it makes you feel 
better."

It is as a rejuvenation treatment that DHEA has obtained the 
most publicity these days -- including national television 
coverage as a miracle anti-aging treatment. But no one 
expects conclusive evidence any time soon, since it would be 
very difficult to conduct a clinical trial to prove that a 
treatment extended the human lifespan. Also, DHEA has been 
around so long that it is largely unpatentable, so most 
companies will be unwilling to spend the money needed to 
prove that it is effective. [However, Genelabs Technologies 
Inc., known in the AIDS community for its earlier testing of 
"compound Q," is developing DHEA as a treatment for lupus.] 
This leaves DHEA in a twilight zone as far as legality and 
access go. 

It is this lack of data and the fact that DHEA is moving out 
into the mainstream that may also account for what DHEA 
advocates say is the FDA's jitteriness about the substance. 
As long as DHEA use was perceived as restricted to a small 
class of individuals, the FDA would leave it alone. As one 
life-extension advocate put it somewhat crassly, as far as 
the FDA goes, "if you are HIV you can do anything you want, 
you have total immunity."

"As long as DHEA remained within the HIV community, the FDA 
could acquiesce," says Steven Fowkes. "But now that it is 
being promoted as a cure-all for everything under the sun, 
the FDA feels obligated to take action. DHEA has crossed over 
from the HIV community into the mainstream where normal 
healthy *voters* will be using it en mass." It is that en 
mass use that Fowkes says worries the FDA most. That is in 
keeping with the FDA's institutional mandate, to protect the 
public health; if everyone starts using an unproven 
substance, the FDA gets nervous. 

Future access to DHEA for people with AIDS may now depend on 
whether or not the DEA defines it as an anabolic steroid. 
Ironically, if DHEA does help build lean body mass and 
prevent AIDS wasting, that could be the very thing that makes 
it almost impossible for U.S. citizens to obtain.


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