AIDS TREATMENT NEWS Issue #253, August 23, 1996
   phone 800/TREAT-1-2, or 415/255-0588


CONTENTS:

Nelfinavir Protease Inhibitor Study Recruiting

Five-Drug or Six-Drug Antiretroviral Therapy - Conversation 
with Steven Scheibel, M.D.

1592 -- New Experimental Antiretroviral

Medical Marijuana: California Update

Calendar of AIDS Research and Treatment Meetings, Late 1996 
and Beyond


***** Nelfinavir Protease Inhibitor Study Recruiting

A new trial of nelfinavir -- VIRACEPT(TM) -- the experimental 
protease inhibitor being developed by Agouron 
Pharmaceuticals, Inc., is now recruiting 200 volunteers with 
CD4 count under 100 (measured any time in the last 90 days), 
who are already taking nucleoside analog drugs (AZT, ddI, 
ddC, d4T, or 3TC). This trial is being conducted in eight 
U.S. cities: Berkeley, Chicago, Dallas, Fort Lauderdale, Los 
Angeles, New York City (2 sites), San Francisco, and St. 
Paul.

All of the volunteers will receive the same dose of 
nelfinavir, 750 mg three times a day. Half of them will be 
randomly assigned to stay on the nucleoside analogs they are 
currently using; the other half will be assigned to switch to 
different nucleoside analogs.

For more information, including the specific sites and 
contact numbers, call 800/501-2474, then dial 1 for a 
recorded message.


***** Five-Drug or Six-Drug Antiretroviral Therapy -- 
Conversation with Steven Scheibel, M.D.

by John S. James

A small clinical trial and observational study in San 
Francisco (1) reported very good HIV suppression with 
regimens of as many as six antiretrovirals. We asked Steven 
F. Scheibel, M.D., one of the physicians who conducted these 
studies, for more recent information than is available in the 
published Vancouver conference abstract.

ATN: We understand that you tried the same five-drug 
combination in two different groups of patients. First, could 
you describe the study with patients who were recently 
infected?

Dr. Scheibel: We treated six patients who were recently HIV-1 
infected (within the past 6 months), with a low-dose 
combination of AZT, ddI, ddC, and interferon-alpha. Most of 
these patients were also receiving full dose 3TC. For this 
small group of recent seroconverters, there was a mean 4.5 
log decrease in plasma HIV-1 RNA at an average followup of 
six months. All these patients attained undetectable HIV RNA 
as measured by the Roche Ultradirect Monitor assay, which has 
a limit of detection of 10 copies/ml of plasma.

ATN: But wouldn't recently infected patients be expected to 
have a viral load decline anyway, even without treatment?

Dr. Scheibel: Even though there may be a drop in plasma HIV 
RNA in untreated recent seroconverters, there is still a 
measurable HIV RNA level. Overall, in the absence of 
treatment, one would expect to find a one to two log 
reduction in viral load [in patients like those who were 
treated]. Our results suggest that most recent seroconverters 
can reach undetectable viral load with this treatment -- 
accompanied by preservation or restoration of CD4 cells. And 
this was accomplished without using a protease inhibitor, 
reserving that class of drugs for later use if needed.

ATN: What other results did you find?

Dr. Scheibel: We did a lymph-node biopsy on one patient, at 
week 78, and found a normal architecture, with no evidence of 
HIV by in situ hybridization.

ATN: What about persons who have been infected for longer?

Dr. Scheibel: We also conducted extended observation of 15 
patients with prolonged HIV infection. They were on the above 
regimen, and most were also taking one of the approved 
protease inhibitors. They had a mean drop in HIV RNA of 3.5 
log. Many of these patients had undetectable HIV RNA levels 
when tested with the Roche Ultradirect Monitor assay.

ATN? What research should be done next? What are your future 
plans?

Dr. Scheibel: Once the plasma HIV RNA level is consistently 
negative, quantify the HIV proviral DNA load, and note 
changes in proviral DNA with combination antiretroviral 
therapies. The proviral DNA load is a measure of the 
reservoir cells which must be eliminated prior to stopping 
combination antiretroviral therapy.

References

1. Saget BM, Elbeik T, Guthries J, Drews B, and Scheibel S. 
Dramatic suppression of HIV-I plasma RNA using a combination 
of zidovudine, didanosine, zalcitabine, Epivir, and 
interferon-alpha in subjects with recent HIV-I infection. XI 
International Conference on AIDS, Vancouver, July 7-12 
[abstract # We.B.533].


***** 1592 -- New Experimental Antiretroviral

by John S. James

An experimental drug code-named 1592U89 (or 1592 for short) 
is a new kind of nucleoside analog which appears to have a 
much stronger anti-HIV effect than AZT, ddI, or other 
approved nucleoside analogs. It is now in phase I/II human 
testing, with one trial giving the drug to about 80 patients. 
Volunteers have had average viral load reductions of about 95 
to 99 percent (approximately 1.5 to 2.2 logs), and average 
CD4 count increases of 79 to 127, at four weeks of treatment 
with this drug alone, and this improvement was sustained for 
the remaining eight weeks of the study. The drug has a short 
but acceptable half life in the blood (1 to 1.3 hours in 
early human tests; a shorter half life usually means more 
frequent doses are needed, but the results above were 
obtained with no more than three times daily dosing), and a 
fairly good ability to cross the blood-brain barrier.

The patients in this trial had CD4 counts of 200-500, and 
less than 12 weeks of prior use of AZT.

1592 is being developed by Glaxo Wellcome. There is growing 
interest in the possibility of compassionate-use access to 
this drug for patients who have failed other treatment 
options.

References

Saag M, Lancaster D, Sonnerborg A, and others. Preliminary 
data on the safety and antiviral effect of 1592U89, alone and 
in combination with zidovudine (ZVD) in HIV-infected patients 
with CD4+ counts 200-500/mm3. XI International Conference on 
AIDS, Vancouver, July 7-12 [abstract # Th.B.294].

McDowell JA, Symonds WT, LaFon SW. Single-dose and steady-
state pharmacokinetics of escalating regimens of 1592U89 with 
and without zidovudine. XI International Conference on AIDS, 
Vancouver, July 7-12 [abstract # Mo.B.1140].


***** Note to Readers

We postponed articles on the recently announced important 
discoveries involving the co-receptor CKR-5, on the August 2 
final report of The Keystone National Policy Dialogue on 
Establishment of Studies to Optimize Medical Management of 
HIV Infection, and on Vancouver conference materials, to 
allow further checking and to make sure that our information 
is as current as possible.


***** Medical Marijuana: California Update

by John S. James

As we reported in our last issue, on August 4 the Cannabis 
Buyers' Club in San Francisco was raided by the office of 
California Attorney General Dan Lungren, who acted without 
informing San Francisco police and city officials. The club 
is still closed, depriving thousands of people with AIDS, 
cancer, and other major illnesses of safe access to medical 
marijuana. Some have collected their documentation and 
applied again at much smaller buyers' clubs in Oakland and 
Santa Cruz; many others have had to buy marijuana on the 
streets, at considerable risk for persons who are unfamiliar 
with the street dealer scene and also are seriously ill. Many 
of their stories have been told in the major news media.

We have seldom seen an issue which left people more angry and 
upset. There is near-universal revulsion toward the 
politically ambitious state attorney general and the other 
California officials who are widely seen to have acted for 
political purposes in depriving many people with major 
illnesses of a treatment vitally important to them.

There is widespread agreement that the important issues now 
are (1) access to marijuana for those with urgent medical 
need, (2) return of the confidential medical records of 
almost 12,000 people, which were seized August 4, and (3) 
passage of California Proposition 215 in the November 
election, to make it clear that doctors and patients who use 
marijuana for legitimate medical purposes are not criminals 
under California law. Since the raid, at least two major 
medical organizations -- the San Francisco Medical Society, 
and the California Academy of Family Physicians -- have 
publicly supported Proposition 215. No major medical 
organization has opposed it.

On August 9 the Cannabis Buyers' Club answered charges 
against it. For example, on the allegation that they sold to 
teenagers, CBC said that the teenager was given the marijuana 
by his mother, an undercover narcotics officer who bought it 
at the club. On the allegation that there were sales to non-
medical users, the CBC admitted that some had slipped through 
with fraudulent documentation, and that the CBC needs to 
tighten its procedures.

On August 15 the San Francisco city government rejected a 
proposal to declare a state of medical emergency in order to 
allow the CBC to operate. AIDS prevention groups were 
concerned that this declaration might cause needle exchange 
in San Francisco to be shut down, since it now operates under 
a similar declaration of medical emergency, despite 
opposition from Lungren.

Persons with a documented medical need for medical marijuana 
may still be able to get it through other cannabis buyers' 
clubs; see our list of California organizations, below. Also, 
note the list of organizations working for passage of 
Proposition 215.

Comment

Opponents of Proposition 215 argue that medical marijuana is 
being used as a wedge issue to legalize drugs. (Incidentally, 
a similar argument is used against needle exchange.) This is 
hard to understand, since morphine and other drugs are widely 
used medically, without that causing any push toward their 
legalization for non-medical purposes. The public can easily 
separate the issues of urgent medical need vs. recreational 
use.

There is also widespread misunderstanding of the role of 
Marinol(R) (dronabinol), a legal prescription drug which 
contains THC, a major active ingredient of marijuana; 
opponents of medical marijuana say patients should use 
Marinol instead. But anyone who knows the people affected 
realizes that because individual patients are different, some 
can use marijuana but not Marinol (and others can use Marinol 
but not marijuana). The appropriate medical care is to have 
both available, so that individuals can use whichever works 
best for them. (Marinol is believed to be about three times 
as expensive as marijuana to use; we could not confirm this 
figure as marijuana prices and potencies vary greatly.)

Meanwhile, the Federal government continues to block medical 
research into medical use of marijuana, almost certainly for 
political reasons. And under President Bush, the Federal 
government closed its emergency medical access program which 
had been running well until then; President Clinton, who "did 
not inhale" and does not want the marijuana issue used 
against him again, has been unwilling to reconsider the 
Federal hostility toward medical access, despite overwhelming 
public support for it.

On August 15 Clinton's new drug czar, retired Army general 
Barry McCaffrey, attacked Proposition 215 in a press 
conference on Haight Street in San Francisco, saying "There 
is not a shred of scientific evidence that shows that smoked 
marijuana is useful or needed," according to the SAN 
FRANCISCO CHRONICLE, August 16. While that statement is easy 
to refute, the main issue is that information is indeed 
lacking because the U.S. has prohibited medical research on 
how to use marijuana as medicine.

While preparing this article we checked the literature on 
adverse effects of marijuana. Much of what we found is 
scientifically ludicrous. This literature is filled with 
reports of a handful of people (sometimes only one) who had 
smoked marijuana and were diagnosed with some illness -- with 
the implication that marijuana was a likely cause. Since 
millions of people receive medical care for serious 
illnesses, and many of them smoke marijuana, there must be 
hundreds of thousands in both categories by chance alone; 
finding a handful of examples proves nothing. What this 
literature does show is the desperate grasp for something, 
anything, that can be used as scientific cover for political 
efforts to keep the drug wars going.

The real fear may be that medical marijuana could indeed be a 
wedge issue -- not to legalize drugs, but to allow rational 
discussion of the overall costs and benefits of the current 
"war on drugs" approach to policy, and creative consideration 
of new options. The medical issue could open doors to re-
thinking which otherwise are closed, since it is almost 
impossible to demonize sick people who use an illegal drug 
for urgent medical reasons, and much easier to demonize other 
users.

But any change threatens powerful interests, since the war on 
drugs has become an economic base for major industries, 
including law enforcement, unprecedented prison operation and 
construction, and a whole cluster of supporting economic 
activity -- as well as a funding stream for many government 
bodies through seized property, and a benefit to politicians 
and the press, who can use police stories to distract and 
entertain the public. In addition, the multi-billion dollar 
illegal drug industry absolutely depends on prohibition, as 
it could not exist otherwise; and this industry has influence 
even though it is illegal. All this could be threatened by a 
re-thinking of drug policy free of the overlay of 
demonization. The focus could then be on the costs we all pay 
in the misdirection of resources and the degradation of our 
quality of life.

What shapes certain kinds of institutional madness is empire 
building -- the normal tendency for institutions (both public 
and private, legal and illegal) to expand their role, 
influence, power, and prestige. What drives this process is 
the natural desire of individuals to get ahead, to become 
more important in their jobs. Growth is not wrong, but 
without effective public scrutiny, institutions can become 
self-perpetuating -- expanding without regard to any public 
purpose, and becoming parasitic, wasteful, and cruel.

All eligible Californians have a vital interest in 
registering and voting in this election -- whatever they 
might think of certain candidates on the ballot. Proposition 
215 might open doors to new thinking beyond drug policy, on 
the larger issues of dysfunctional institutions and their 
tragic consequences for national and personal life.

Cannabis Buyers' Clubs in California

** Oakland CBC, P.O. Box 24590, Oakland, CA 94623, phone 
510/832-5346, fax 510/986-0534.

** Santa Cruz CBC, 201 Maple St., Santa Cruz, 408/429-8819.

** CBC Marin, contact Lynnette Shaw, 415/253-4374 
voicemail/pager.

** Los Angeles CBC, 8159 Santa Monica Blvd., Suite 200, West 
Hollywood, CA 90046, phone 213/654-8910, fax 213/654-7833, 
email simler@ix.netcom.com, web site 
http://www.medicalmarijuana.org .

** Wo/Men's Alliance for Medical Marijuana (WAMM), 1803 
Mission Street, Suite 553, Santa Cruz, CA 95060, phone/fax 
408/423-5413, email WAMMCA@aol.com . (Note: This group does 
not identify as a "buyers' club" per se; WAMM does not charge 
for dispensing medical marijuana, but accepts donations.)

Note: San Francisco's Cannabis Buyers' Club can be reached 
through Californians for Compassionate Use (see contact 
information below). Due to an injunction against it, the CBC 
is not distributing medical marijuana at this time, but is 
focusing instead on passage of Proposition 215.

Organizations Working for Proposition 215

** Californians for Medical Rights (CMR), 1250 Sixth Street 
#202, Santa Monica, CA 90401, 310/394-2952, fax 310/451-7494. 
CMR is the official sponsor of Proposition 215. Other groups 
are also working for this Proposition, but they are separate.

** Californians for Compassionate Use, 1444 Market Street, 
San Francisco, 415/621-3986, fax 415/621-0604, email 
cbc@marijuana.org, web site http://www.marijuana.org .

** Southern Californians for Compassionate Use (SCCU), 8159 
Santa Monica Blvd., Suite 200, West Hollywood, CA 90046, 
phone 213/874-4155, fax 213/874-4211, email 
simler@ix.netcom.com, web site 
http://www.medicalmarijuana.org .

** Cannabis Action Network, 2560 Bancroft Way #46, Berkeley, 
CA 94704, phone and fax 510/486-8083, email caninfo@ccnet.com 
