AIDS TREATMENT NEWS Issue #259, November 15, 1996
   phone 800/TREAT-1-2, or 415/255-0588

CONTENTS:

Birmingham UK Drug Therapy Conference -- Early Report

Federal Team Developing Treatment Principles for HIV 
Infection

1592: Two Studies Recruiting

The New Antiretroviral Arsenal

Medical Marijuana Wins in California and Arizona

FDA  Internet Regulation? Public Comment Accepted until 
December 16

AZT Twice-Daily Tablets Approved; Dosing Concerns

Retroviruses Conference: Press Deadline December 6

Qigong Program on San Francisco KQED TV, Beginning December 7


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***** Birmingham UK Drug Therapy Conference -- Early Report

by John S. James

The important 3rd International Congress on Drug Therapy in 
HIV Infection took place in Birmingham, UK, November 3-7; we 
could not attend and are still gathering information as we go 
to press November 12. There was much interest in studies 
relevant to the complete suppression of HIV replication by 
drugs.

A small but widely discussed study at the University of 
Amsterdam found that antiviral treatment which reduced viral 
load to undetectable levels in the blood, also reduced viral 
load to undetectable levels in lymph tissue. This was found 
in six out of six patients in a substudy of a larger trial. 
The lymph tissue was taken by a biopsy of the tonsils (which 
is much less invasive than the conventional procedure of 
removing a lymph node), before starting treatment and again 
after six months of treatment.

Researchers at the University of Minnesota developed the 
methodology to measure HIV in lymph tissue from tonsils; see 
recent paper by Haase AT, Henry K, Zupancic M and others, 
"Quantitative Image Analysis of HIV-1 Infection in Lymphoid 
Tissue," SCIENCE, November 8, 1996, pages 985-989.

Undetectable HIV viral load in the lymph nodes does NOT mean 
that the virus has been eradicated -- only that it is not 
actively reproducing. This viral load test only looks for 
viral particles; it does not detect the viral DNA that is 
still in the patients' cells -- ready to start up the 
infection again if the drugs are stopped. No one knows 
whether or not all these cells will eventually be eliminated 
by the body, if replication can be stopped for long enough.

While the growth of the virus is being completely suppressed, 
drug resistance apparently does not develop. The virus 
develops resistance when it is able to reproduce to some 
degree in the presence of the drugs, since then the viral 
variants which happen to be resistant to those drugs have a 
selective advantage, and can replace the more susceptible 
virus.

These results are not surprising, as there have long been 
indications that if viral replication is being suppressed in 
the blood by antiretroviral drugs, it is also suppressed in 
the lymph nodes (where there is much more HIV than in the 
blood, and where the virus is more important in the 
development of disease). And no one would expect the drug 
resistance of the virus to increase if the virus is not 
reproducing. But it is important to get direct evidence, 
since these questions are central to the interpretation of 
viral load tests and the management of therapy.

Note: The drug combination used in this University of 
Amsterdam study was ritonavir, AZT, and 3TC, in volunteers 
who had not used any antiretroviral before. However, there is 
nothing special about this particular combination; all 
evidence suggests that what is important is reducing the 
viral replication essentially to zero and keeping it there, 
using whatever drugs can do so for a particular patient. 
Similar suppression of replication has also been achieved 
with other combinations using a different protease inhibitor 
-- or even no protease inhibitor at all.

The main problem now is that some patients are more difficult 
to treat -- especially those with more advanced HIV disease, 
those who have already developed resistance to existing 
antiretrovirals, and those who cannot tolerate the drugs. 
This is why the problem of HIV treatment is not solved, 
despite the good results in some people. We need continuing 
development of better drugs -- with stronger and more durable 
antiviral effects, and/or less toxicity, and/or different 
resistance profiles than existing treatments, and/or drugs 
which may not be superior on the average but do work for some 
people when others treatments do not. And then of course 
there are still the economic barriers of getting effective 
treatments to those who need them.

More work is also needed on measurement of HIV in lymph 
tissue, since the most sensitive tests are quite difficult to 
do at this time.

There has long been an ongoing debate about the importance of 
aiming specifically for complete suppression of viral 
replication, vs. being willing to compromise on partial 
suppression due to practical concerns of toxicity, cost, and 
onerous compliance with regimens of three drugs or more. 
Professional opinion now seems to be moving more strongly 
toward the importance of complete suppression whenever 
antiviral therapy is used, because of the danger that 
otherwise the patients' virus will develop resistance to the 
drugs one by one, and each drug in turn will be lost for that 
person. This probably means that when therapy is begun, it 
will usually be with three or more drugs started together 
(instead of starting with one or two, then adding other drugs 
when the first ones fail); those who have already used 
antivirals will need to start or add combinations of at least 
two new drugs they have not seen before. What counts is 
keeping the viral load essentially at zero, whatever 
treatment that requires, because otherwise the virus will 
eventually escape the control of the drugs.

Extending and applying these principles to the treatment of 
many different patients in different situations, given the 
limitations of the drugs available and the practical 
limitations imposed by the difficulties of therapy, will be a 
central challenge in AIDS medicine for the next several 
years.


***** Federal Team Developing Treatment Principles for
HIV Infection

by John S. James

The Office of AIDS Research (OAR) of the U.S. National 
Institutes of Health has selected a panel "to make 
recommendations regarding initiation of treatment; 
suppression of HIV replication; minimizing or preventing 
emergence of drug-resistant HIV variants; prolonging 
effectiveness of therapy; and addressing the public health 
consequences of transmission of multi-drug resistant 
variants."

"The panel's activities will involve a series of meetings and 
analysis of the most recent available data. The panel is 
expected to work over the next several months to develop 
these recommendations, which will help health care 
practitioners and HIV-infected individuals make informed 
decisions about treatment options. It is also anticipated 
that the recommendations of this panel will assist public and 
private health care payers in providing reimbursement for 
essential care for HIV-infected patients."

The "NIH Panel to Define Principles of Therapy of HIV 
Infection" has 24 members and is chaired by Charles 
Carpenter, M.D., of Providence, Rhode Island; its executive 
secretary is Mark Feinberg, M.D., Ph.D., of OAR. There are 
two community representatives: Dawn Averitt, of Women's 
Information Service & Exchange (WISE) of Atlanta, and Mark 
Harrington of Treatment Action Group (TAG) of New York. Three 
panelists are from Europe and Australia, with most of the 
U.S. members from the East Coast.

The panel's first meeting is November 13 and 14 in 
Washington, during which the panelists will hear more than 30 
presentations on the current state of scientific knowledge, 
focusing mainly on recent information learned too late for 
presentation at the Vancouver international conference in 
July.

The meeting occurs after this issue of AIDS TREATMENT NEWS 
goes to press, and OAR does not plan to issue a report of 
this particular meeting (clearly there will be a report from 
the panel eventually). But the list of presentations (from 
the draft agenda released by OAR) gives an excellent overview 
of the state of the science today, of some of the issues 
considered most relevant to designing the best possible 
treatments for HIV disease. The titles are listed 
chronologically from a November 11 draft agenda, but because 
of lack of space we did not include the names and 
affiliations of the presenters.

Wednesday November 13, 1996:

Session I: Virus and T Cell Population Dynamics in HIV 
Infection

* HIV Replication Dynamics: Virus Turnover and Implications 
for Antiviral Therapy

* Analysis of Tissue Reservoirs of HIV Infection

* Human T Cell Populations in HIV-Infected and Uninfected 
Individuals

* Regenerative Potential of Human T Cell Populations

* Natural History of T Cell Depletion in AIDS

* Maintenance and Loss of T Cell Homeostasis in HIV Infection

* T Cell Replication Senescence in HIV Infection

Session II: The Relationship Between HIV Replication and 
Disease Progression

* Performance Characteristics and Variability of the 
Quantiplex (bDNA) Assay for Plasma HIV-1 RNA

* Performance Characteristics and Variability of the Amplicor 
(RT-PCR) Assay for Plasma HIV-1 RNA

* Primary HIV-1 Infection and the Establishment of the 
Replication "Set Point"

* Serum HIV-1 RNA Levels and Progression to AIDS

* Relationship between Plasma and Cellular HIV-1 RNA Levels 
and Progression to AIDS

* Population-Based Studies of Plasma HIV-1 RNA Levels

* Plasma HIV-1 RNA Levels Predict Risk of Disease Progression 
and Survival

Section III: Relationship between Therapy-Induced Decreases 
in HIV-1 Replication and Protection from Disease Progression

* Correlation Between Decline in HIV-1 RNA Levels and 
Clinical Outcomes (2 presentations)

* Cross-Study Comparisons of Therapy-Induced Changes in Viral 
Load, CD4 T Cell Counts and Clinical Progression

Thursday November 14, 1996:

Session IV: Therapy-Induced Changes in CD4 T Cell Levels and 
Recovery of Immunologic Function

* The Magnitude and Limits of Therapy-Induced CD4 Cell 
Increases

* Recovery of T Cell Numbers and Function Following Antiviral 
Therapy

Session V: Strategies to Delay or Prevent Antiviral Drug 
Resistance

* Understanding and Overcoming HIV-1 Antiviral Drug 
Resistance

* Combination Antiviral Therapy and Antiviral Drug Resistance

* Detection of Drug-Resistant HIV Variants (2 sessions)

Session VI: Protease Inhibitors Resistance and Cross 
Resistance

* HIV-1 Protease Inhibitors Resistance (2 sessions)

Session VII: Combination Antiviral Therapy of Established 
HIV-1 Infection

* Combination Therapy of Primary HIV-1 Infection

* Antiviral Therapy of Primary HIV-1 Infection

* Combination Nucleoside Analog Therapy

* Combination Nucleoside Therapy: Recent Experience and 
Future Prospects

* Combination Therapy and Non-Nucleoside RT Inhibitors

* Long-Term Suppression of HIV-1 Replication by Combination 
Therapy

* Recent Results with Protease Inhibitors

* New Antiviral Therapies (2 presentations)

* Closing Remarks


***** 1592: Two Studies Recruiting

1592U89, usually called 1592, is an experimental nucleoside 
analog drug (in the same class as AZT) with much community 
interest, for several reasons. First, research has shown that 
under some conditions at least, it can produce a 2-log (100 
fold) viral reduction with just one drug. Also, it has good 
penetration of the blood-brain barrier, suggesting potential 
use for treating AIDS-related dementia. And a third reason 
for the intense interest is that 1592 is a new possible 
treatment for persons who do not have other options.

[Note: On November 12 THE WALL STREET JOURNAL published a 
major article on 1592, "Why Isn't Glaxo's New AIDS Drug Ready 
Yet," by Michael Waldholz, page B1; it asks why 1592 has been 
in research much longer than other new AIDS drugs but is not 
expected to be marketed until almost two years from now, and 
is not being made available through expanded access for those 
with no other treatment options.  Activists suspect that the 
drug is being delayed to avoid competing with AZT and 3TC; 
Glaxo says it did not know until about a year ago how much 
more powerful this drug is than others. It is remarkable how 
Glaxo's arguments against expanded access resurrect those 
that were used years ago against other AIDS drugs, and long 
ago abandoned.]

Glaxo Wellcome is now running two preliminary trials of 1592:

Protocol 2003

This trial will test the antiretroviral activity of 1592 in 
40 persons nationally who are already using certain approved 
nucleoside analog drugs. Forty persons will be enrolled in 
this study, and all will receive the same dose of 1592 (300 
mg orally twice a day), in combination with other nucleoside 
analogs. There is no placebo. In order to enter this study, 
volunteers must be at least 13 years old, must have a CD4 
count of at least 100, and must have a viral load of at least 
30,000.

But there are complex entry criteria based on pre-existing 
antiretroviral therapy; for example, anyone who has used a 
protease inhibitor, or a non-nucleoside reverse transcriptase 
inhibitor (e.g. nevirapine) is ineligible. In order to enter 
this study, a person must fit in at least one of the four 
following categories:

* At least 12 months of AZT monotherapy;

* At least 6 months of 3TC and 12 months of AZT;

* At least 6 months of ddI monotherapy;

* At least 6 months of d4T and 12 months of AZT.

Anyone who has had other antiretroviral treatments is not 
eligible for this trial.

The trial is being run in eight cities; we list the state, 
city, study coordinator, institution, and phone number at 
each site. For more information, call the contact person 
listed:

* California: Greenbrae (Alison Clayton, Marin County 
Specialty Clinic, 415/499-7377);

* California: Los Angeles (Scott Brooks, Kraus Medical 
Partners, 213/930-2324);

* California: San Francisco (Debbie Hildebrandt, ViRx, Inc., 
415/353-5623 or 415/474-4440);

* Florida: Ft. Lauderdale (Keith Huber, R.N., North Broward 
Hospital District, 954/467-3006 ext. 240);

* Florida: Maitland (Neena Griffin, R.N., Central Florida 
Research Initiative, 800/868-3483 ext. 3, or 407/647-3960);

* Georgia: Atlanta (Laura Ray, AIDS Research Consortium of 
Atlanta, 404/876-2317 ext. 329);

* Kentucky: Lexington (Karen Meekins, R.N., University of 
Kentucky Medical Center, 606/323-3933);

* New York: New York (Ann Marshak, Beth Israel Medical 
Center, 212/420-4519).

Protocol CNAB3001

This is a 90-patient phase III study for persons with HIV-
associated dementia. Volunteers will be able to continue 
their current antiretroviral treatment in most cases, and 
will be randomized to receive 1592 or placebo for 12 weeks. 
After the 12 weeks, all participants will receive 1592 for 40 
weeks. The dose of 1592 used in this study is 600 mg twice a 
day.

To be eligible, persons must be between 18 and 65 years old, 
and must have been stable on their current antiretroviral 
treatment for at least six weeks. There are a number of 
exclusion conditions, especially for certain abnormal 
laboratory tests, or for certain unrelated illnesses.

For more information, call the contact person at a site which 
you could attend:

Baltimore (Tish Nance, 410/955-7464);

Chapel Hill (Wendy Robertson, 919/966-6727);

New York - Columbia University (Ronda Freedman-Clouse, R.N. 
212/960-2230);

New York - Mt. Sinai (Jessica Moise, 212/241-0784);

San Diego - (Mary Anne or Mary McCarthy or Dr. Stephen Brown, 
619/543-5059);

San Francisco (Dr. Richard Price, 415/206-3208);

St. Louis (Meridith Glicksman, 314/362-9733).


***** The New Antiretroviral Arsenal

by Denny Smith

In less than one year, the options for managing HIV have more 
than doubled. The number of drugs approved to treat HIV 
infection has risen to nine, with two others now available to 
qualifying persons under expanded-access programs. We 
prepared this quick guide to help people orient themselves to 
the various drugs and their different names; these brief 
descriptions could not possibly be complete, and people with 
HIV must work with their physicians to be aware of the 
different possible side effects, and the other instructions 
which are essential for using these treatments correctly.

Generally no anti-HIV drug should be used alone, given the 
ease with which HIV develops resistance. Some drug 
combinations have been proven more effective--or have fewer 
side effects--than others. But much is still unknown about 
combination therapy, and most people must experiment 
intelligently with different combinations to see what will 
keep both their viral load and treatment-related toxicities 
as low as possible.

Most clinicians we know are now making treatment 
recommendations based on drug tolerance and viral load, 
rather than CD4 cell counts. The CD4 count is now used 
largely for deciding when to use prophylaxis therapies to 
prevent opportunistic infections.

We have listed the reverse transcriptase inhibitors first, 
followed by the protease inhibitors, followed by hydroxyurea, 
which was originally developed as an oncology drug, but which 
may work in a unique manner against HIV. Important note: The 
side effects described for each entry below are only the most 
common or important ones. Physicians and patients should 
always be prepared for other toxicities, which are described 
at length in the product inserts available at any pharmacy.

Reverse Transcriptase Inhibitors

These drugs work by inhibiting an enzyme -- reverse 
transcriptase -- which the virus needs to replicate. 

* AZT, also called zidovudine, is marketed under the brand 
name Retrovir(R). AZT has been combined with all other 
antiretrovirals and may work especially well in combination 
with 3TC, indinavir, nevirapine or delavirdine. AZT is 
valuable for treating cognitive problems caused by HIV 
because it penetrates the central nervous system better than 
most of the other drugs. It can cause headaches and stomach 
upset, but these often go away after a couple weeks. Over 
extended periods of use, it can cause anemia (low production 
of red blood cells), neutropenia (low white cells) and 
myopathy (damage to muscle fibers). These problems resolve if 
the drug is discontinued. The usual prescription for AZT has 
been two capsules (200 mg) taken three times a day, but 
Glaxo-Wellcome will soon be offering a 300 mg capsule that 
can be taken twice daily. The dose used for treating 
cognitive or motor slowing or dementia is twice the regular 
dose: 1200 mg a day.

* ddI, also known as didanosine, is sold under the brand name 
VIDEX(R). ddI can be combined with any other antiretroviral, 
but may work especially well with d4T, nevirapine or 
hydroxyurea. However, ddI, ddC, and d4T can each cause 
peripheral neuropathy and pancreatitis, so any combination of 
these drugs must be carefully monitored. If you experience 
abdominal pain or tingling and numbness in your toes or 
fingers, stop taking these drugs and call your healthcare 
provider; otherwise, long-term damage may result. The usual 
prescription for ddI is two tablets (125 or 200 mg, depending 
on body weight) taken twice a day on an empty stomach with 
water.

* ddC, also called zalcitabine, is sold as HIVID(R). ddC can 
be combined with any other antiretroviral, but must be used 
cautiously with ddI or d4T, since all three drugs can cause 
neuropathy or pancreatitis. If you experience abdominal pain 
or tingling and numbness in your toes or fingers, stop taking 
these drugs and call your provider; otherwise, long-term 
damage may result. The usual prescription for ddC is one 
tablet (0.75 mg) taken three times a day.

* d4T, also known as stavudine, is marketed as Zerit(R). d4T 
can be combined with most other antiretrovirals and may work 
especially well with ddI or nevirapine. However, d4T must be 
used cautiously with ddI or ddC, since all three drugs can 
cause neuropathy and pancreatitis. If you experience 
abdominal pain or tingling and numbness in your toes or 
fingers, stop taking these drugs and call your provider; 
otherwise, long-term damage may result. The usual 
prescription for d4T is one capsule (30 or 40 mg, depending 
on body weight) taken twice a day.

* 3TC, also called lamivudine, is marketed as Epivir(R). 3TC 
can be combined with any other antiretroviral and may work 
especially well with AZT,  nevirapine or delavirdine. 3TC may 
resensitize HIV to AZT in people whose virus has become 
resistant to AZT. It can cause headaches and insomnia in some 
people, but these usually go away after a few weeks. The 
usual prescription for 3TC is one tablet (150 mg) taken twice 
a day.

Non-Nucleoside Reverse Transcriptase Inhibitors

* Nevirapine is sold under the brand name Viramune(R). 
Nevirapine can be combined with most other antiretrovirals, 
but has not been widely studied in combination with 
delavirdine, hydroxyurea or the protease inhibitors. It may 
work especially well with AZT, ddI, d4T, or 3TC. Nevirapine 
can cause a serious rash, but this may be avoided by starting 
with a low dose, one tablet taken once a day for two weeks, 
and then doubled to the usual prescription: one tablet (200 
mg) twice a day.

* Delavirdine is available only to people with CD4 counts of 
300 or less through an expanded-access program run by Upjohn, 
which calls the drug Rescriptor(R). An FDA advisory committee 
will consider full approval on November 22. Delavirdine can 
be combined with most other antiretrovirals, although it has 
not been widely studied in combination with nevirapine, 
hydroxyurea or the protease inhibitors.  It may work 
especially well with AZT and 3TC. Like 3TC, delavirdine may 
resensitize the virus to AZT in people who have become 
resistant to that drug. Like AZT, delavirdine may be useful 
for HIV-related cognitive problems because it can penetrate 
the central nervous system. And like nevirapine, it can cause 
a rash in some people. The prescription for delavirdine is 
four pills (400 mg) taken three times a day.

Protease Inhibitors

These drugs target a different enzyme of the virus -- the HIV 
protease -- which is essential for HIV to make working copies 
of itself. More than with most drugs, it is very important 
not to miss doses of the protease inhibitors.

* Indinavir is sold under the brand name Crixivan(R). 
Indinavir can be combined with most other reverse 
transcriptase inhibitors, but has not been widely studied in 
combination with nevirapine or delavirdine, or hydroxyurea or 
the other protease inhibitors. It should definitely not be 
combined with ritonavir. Indinavir can cause stomach upset, 
kidney stones and generalized discomfort, although drinking 
plenty of fluids may prevent the kidney stones. It should be 
used with caution with certain other medications, so make 
sure your provider knows about everything you are taking. The 
usual prescription for indinavir is two capsules (800 mg) 
taken three times a day on an empty stomach with a large 
glass of water. Try not to miss any doses of this drug, or 
the virus could quickly become resistant.

* Ritonavir is marketed as Norvir(R). Ritonavir can be 
combined with most other antiretrovirals, but has not been 
widely studied in combination with nevirapine, delavirdine, 
or hydroxyurea. Ritonavir may work especially well with 
saquinavir, but only at doses tested in combination trials, 
and it should definitely not be combined with indinavir. 
There are many other medications that should be used with 
caution or not at all with ritonavir, so tell your provider 
exactly what you are taking. Ritonavir can cause stomach 
upset, generalized discomfort and tingling or numbness around 
the mouth. These might by avoided by starting with a low 
dose, three capsules taken twice a day with food, and adding 
one capsule each dose every couple days until the usual 
prescription is tolerated: six capsules (600 mg) taken twice 
a day. The capsules should be stored in a refrigerator. Try 
not to miss any doses of this drug, or the virus will quickly 
become resistant.

* Saquinavir is sold under the brand name Invirase(TM). 
Saquinavir can be combined with most other antiretrovirals, 
and may work especially well with ritonavir, but only using 
the low doses tested in combination trials. It has not been 
widely studied with hydroxyurea, nevirapine, delavirdine, or 
the other protease inhibitors. It should also be used with 
caution with certain other medications, so make sure your 
provider knows about everything you are taking. Saquinavir 
can cause mild stomach upset and sun sensitivity, but these 
are unusual. The usual prescription for saquinavir--unless 
combined with ritonavir--is three capsules (600 mg) taken 
three times a day with food. The current formulation of 
saquinavir is very poorly absorbed, but taking it with 
grapefruit juice helps to increase blood concentrations. A 
better formulation will probably be available next year. Try 
not to miss any doses of saquinavir, or the virus may become 
resistant.

* Nelfinavir was developed by Agouron Pharmaceuticals; its 
brand name is VIRACEPT(TM). It is available only through an 
expanded-access program to people with CD4 counts of 50 or 
less who can no longer tolerate or benefit from the other 
three protease inhibitors. Nelfinavir can be combined with 
most reverse transcriptase inhibitors, although it has not 
been studied in combination with delavirdine or nevirapine, 
or hydroxyurea. And because it is so recently available, we 
do not know anyone who has tried novel combinations with this 
drug. The criteria by which it is dispensed essentially 
prohibit the combination of nelfinavir with other protease 
inhibitors. It can cause stomach upset or headaches in some 
people, and should used with caution with certain other 
medications. The prescription for nelfinavir is three tablets 
(750 mg) taken three times a day with food.

Miscellaneous

* Hydroxyurea is marketed as Hydrea(R) and is used to treat 
melanoma, leukemia, ovarian, and head and neck cancers. It 
may fight HIV by partially inhibiting a human enzyme, called 
ribonucleotide reductase, which HIV needs. Hydroxyurea may 
work especially well with ddI. Like AZT, hydroxyurea can 
cause anemia and neutropenia, although this is unlikely using 
the low dose usually prescribed for HIV: one capsule (500 mg) 
daily. Note: While hydroxyurea is an approved drug for 
certain cancers, its use with HIV is experimental.


***** Medical Marijuana Wins in California and Arizona

by John S. James

By 55.7% to 44.3%, California voters passed Proposition 215 
to allow medical use of marijuana. Arizona voters passed 
Proposition 200 by a much larger margin, 65.3% to 34.7%. The 
Arizona measure is broader than California's; in addition to 
allowing medical marijuana, it may lead to release of persons 
already in prison for certain nonviolent offenses. It is much 
less well known than the California initiative, because 
supporters in Arizona did not want outside help, due to 
sensitivity of Arizona voters to interference in their 
affairs.

Californians for Medical Rights, the official sponsor of the 
'Yes on 215' campaign, is preparing a brochure for patients 
and doctors "who need to know what Proposition 215 means to 
them. By the same token, we will help to inform people who 
are NOT sick as to why Propositions 215 will not apply to 
them. We don't want anyone to get the wrong idea about this 
new law, and end up putting themselves at risk 
unnecessarily." To leave your name and address to receive a 
copy of the free brochure, call the Proposition 215 Patient 
Information Hotline, 1-888-YES-4-215 (toll free).

No county in California had less than 40% of voters 
supporting the medical marijuana measure, according to a 
voter survey of over 2,000 voters published the day after the 
election (we do not have the final official figures, which 
would include absentee ballots and may differ somewhat from 
the survey). The highest support was in San Francisco, with 
78% of voters interviewed. Los Angeles supported Proposition 
215 by 56%. See the SAN FRANCISCO EXAMINER, November 6, page 
A-24, for a vote breakdown for all counties, and statewide by 
demographics, political beliefs, etc.

Comment

Despite exaggerated statements from both sides suggesting 
that California marijuana laws are now unenforceable, we 
suspect that the main immediate effect of Proposition 215 
will be to create a limited legal defense in court. A state 
proposition cannot overrule Federal laws against marijuana 
for medical or other use. It will be necessary to build a 
national campaign to change Federal laws.

The biggest ultimate impact of these votes may be to open 
doors to rational discussion about the war on drugs. And here 
it is clear that the country desperately needs other policy 
options besides prohibition or official indifference. This 
writer has strongly supported Proposition 215, but would 
never want to see massive television and billboard promotion 
of marijuana. Today with tobacco, companies sanctimoniously 
agree to help keep it from children, while knowing full well 
that their future centrally depends on getting children and 
teenagers to smoke, since few smokers begin as adults -- 
leading to highly sophisticated, lavishly financed corporate 
promotions to children, cleverly designed to stay mostly 
under the radar of civil society.

We need a new category between legal and illegal, for 
activities where adults are clearly allowed to make their own 
decisions, but where public policy is not neutral, 
discouraging an activity by other means than by making it a 
crime (such as by prohibiting routine or large-scale 
promotion). The Supreme Court has made such policies 
difficult, by defining advertising as Constitutionally-
protected "speech" -- making it hard to regulate promotion of 
products such as alcohol, tobacco, or marijuana, without 
first making them a crime and invoking all the deadly baggage 
of prohibition, for no public purpose.

The Proposition 215 demographic breakdowns in the EXAMINER 
survey are fascinating. Sex made little difference, with 
females slightly more supportive of medical marijuana. There 
were big differences by race, with Black most supportive of 
proposition 215, Asian least supportive, and White in the 
middle. By age, support was lowest among voters over 60. 
Voters who currently were paid full-time workers were 
considerably more supportive than those who were not.

But what may be most important was the breakdown by whether 
the voter has children under 18. There was almost no 
difference in support -- only a 2% difference, and the survey 
had a margin of error of 3%. We would have thought that the 
basis of opposition to this proposition would have been 
parents worried that their children could get in trouble with 
drugs. But that is not what happened.

What, then, IS the basis of the opposition to medical 
marijuana, or to this particular initiative? Polls have 
repeatedly shown strong support for the right to use 
marijuana for legitimate medical needs; in view of this 
consistent support, the 55.7% vote in California seems 
disappointing. Supporters should ask the 44.3% who voted 
against Proposition 215 what was on their minds. Addressing 
their objections will be an important part of making this 
initiative work well enough to be an effective national 
model.


***** FDA Internet Regulation? Public Comment Accepted until 
December 16

On October 16 and 17 the FDA held a public meeting, "FDA and 
the Internet: Advertising and Promotion of Medical Products," 
near Washington D.C.; several hundred people attended, mostly 
from industry (apparently there were no more than two AIDS 
community or activist representatives). This meeting has been 
widely reported in the press, but these articles did not tell 
their readers that anyone can submit written comments until 
December 16.

Background about the meeting was published in the Federal 
Register, September 16, volume 61, number 180, pages 48707-
48710. That Federal Register notice included the following 
summary:

"The Food and Drug Administration (FDA) is announcing a 
public meeting to discuss issues related to the promotion of 
FDA-regulated medical products on the Internet. FDA is 
seeking participation in the public meeting and written 
comments from all interested parties, including, but not 
limited to, consumers, patient groups, information vendors, 
manufacturers of FDA-regulated medical products, and health 
care professionals. This meeting and the written comments are 
intended to help guide FDA in making policy decisions on the 
promotion of biologics, human and animal drugs, and medical 
devices on the Internet and the World Wide Web (the Web)."

The meeting was divided into five discussion groups: 
Investigational product information; Chatrooms and 
newsgroups; Additional regulatory issues; Website links; and 
International issues.

A complete transcript of the two-day meeting is available on 
the FDA Web page, http://www.fda.gov

How to Submit Comments

"Submit written comments on the questions to the Dockets 
Management Branch (DMB) (HFA-305), Food and Drug 
Administration, 12420 Parklawn Dr., rm. 1-23, Rockville, MD 
20857. After the meeting, a transcript will be available at 
DMB (address above) between 9 a.m. and 4 p.m., Monday through 
Friday."

We suggest that persons preparing comments examine the 
meeting transcript, available either worldwide through the 
Web or at the FDA's Rockville office, or at least read the 
Federal Register announcement of the meeting, which includes 
the FDA's specific questions for each discussion group.

Comment

>From what we have heard after the meeting, it seems unlikely 
that the FDA will make major attempts to regulate the content 
of medical information on the Internet -- but there is no way 
to know for sure. We are concerned about a number of issues, 
for example:

* Pharmaceutical and other companies may be pressured to 
restrict more of their material to medical professionals -- 
rolling back the movement toward patient empowerment (some 
online material is already restricted). Also, requiring 
registration as medical professionals could greatly limit 
information flow to developing countries, even to medical 
professionals, because doctors there would probably not show 
up as licensed in the databases in the U.S. or other home 
country of the pharmaceutical company.

* Even aside from Internet issues, restriction of information 
about experimental drugs has greatly hindered recruitment in 
clinical trials. Why will doctors refer patients, if they do 
not understand the rationale of the treatment or the trial 
(which companies are often afraid to include in their trial 
announcements, lest they be accused of promotion)? The main 
problem is not in the FDA's intent, nor in the regulations 
themselves, but in overreaction by industry personnel who do 
not know the system very well, and are overly fearful of 
getting their companies, and therefore their own careers, in 
trouble. Formal regulations, or even informal standards and 
expectations, could inadvertently extend and exacerbate this 
problem, unless great care is used.

* The rapidly developing "global village" world has both 
advantages and disadvantages; one of the advantages is a kind 
of world medicine built on local traditions. There have long 
been much greater differences internationally in medical care 
(even between seemingly comparable industrialized countries) 
than the public realizes. Traditionally, if the medicine of 
one's own country does not work for a patient's condition, 
that patient is out of luck. But with world medicine, the 
locally approved treatments will still be tried first, 
because physicians are most familiar with them; but when 
local drugs or procedures are unsuccessful, others can be 
borrowed from countries which have different approved 
protocols, drugs, indications, and diagnostic tests -- 
increasing the overall chance of a successful outcome. Today, 
individual educated patients and activist movements are at 
the leading edge of this change; as world medicine develops, 
it will need to become more institutionalized in order to 
serve more people. But clearly the benefits of world medicine 
are seriously threatened either by medical uniformity imposed 
everywhere, or by blocking information about drugs and 
indications in those countries where they are not approved.


***** AZT Twice-Daily Tablets Approved; Dosing Concerns

by John S. James

On October 25 the FDA approved a 300 mg AZT tablet, intended 
for twice-daily dosing. (AZT is commonly taken as 200 mg 
three times a day in the U.S.) The new dose is intended to be 
more convenient by reducing the three daily doses to two -- 
hopefully improving patients' compliance with their 
physicians' instructions.

There are concerns that twice-daily dosing may not work as 
well as giving the same amount of drug at more frequent 
intervals, because of the greater variation in blood levels 
throughout the day. These concerns are (1) that low trough 
levels could allow viral resistance to develop faster, and 
(2) that higher peak levels after each dose could increase 
side effects. In defense of twice-daily dosing, Glaxo-
Wellcome notes that 250 mg twice daily is the standard AZT 
dose in Europe, that most clinical trials using AZT today use 
twice-daily dosing, and that no differences in safety or 
efficacy was seen in a trial of 320 volunteers which compared 
100 mg every four hours vs. 300 mg every 12 hours for 48 
weeks (the trial was not powered to find differences in 
efficacy, however, and it did not measure viral resistance). 
Glaxo also notes that the new dose is only an option, since 
the previous formulation remains available, and that trials 
to measure the development of viral resistance are now in 
progress or being planned.


***** Retroviruses Conference: Press Deadline December 6

by John S. James

The 4th Conference on Retroviruses and Opportunistic 
Infections, January 22-26, 1997 at the Sheraton Washington 
Hotel in Washington, DC, will probably be the most important 
AIDS conference in the U.S. in 1997. The deadline for 
"community based newsletters" (most AIDS-related newsletters) 
to register as press is December 6. For "all other press," 
(newspaper and TV reporters, freelance writers on assignment, 
etc.) the deadline is January 10, and applications will be 
processed first come first served. Many industry publications 
may not be allowed to register as press in either category. 
There is no on-site registration.

The Community Liaison Subcommittee will review and approve 
the community press applications, and applicants will be 
notified in mid December. This Subcommittee is excellent, but 
only has a limited number of slots to approve.

The bottom line is that anyone who wants to attend this 
conference needs to start making arrangements as soon as 
possible. For more information, obtain the Press Registration 
packet from the Retrovirus Conference Secretariat, c/o 
Infections Diseases Society of America (IDSA), 703/299-0200, 
fax 703/299-0204.

Press rules include no photography, video recording, or 
formal interviews in session rooms or the poster hall, and no 
photography elsewhere except with prior approval. Audio 
recordings are allowed, but not for republication or 
rebroadcast.

For those not going, the published abstracts are scheduled to 
be available on the Internet on January 22, at 
http://www.idsociety.org. The printed abstract book will be 
sent two weeks in advance to all registered press.

Comment

As we have noted in previous articles, some of the press 
rules for this conference are highly unusual and a major 
impediment to rapid, accurate reporting. For almost ten years 
we photographed poster presentations and occasional slides at 
AIDS conferences without ever being told not to. At the 
Vancouver conference we found that a good-quality video 
camera was exceptionally useful, both for recording posters 
and for recording key slides with the accompanying 
discussion. We have taken these pictures only to assure the 
accuracy of our own reporting, never for republication. 
Traditionally, only FLASH photography in oral sessions has 
been banned, for good reason. But at the retroviruses meeting 
the cameras will apparently be limited to interviews in the 
press room, damaging accurate technical reporting for no 
public benefit.

Another major press problem at the Retroviruses conference is 
the requirement that mainstream media register in advance. We 
do not know of any effective way to communicate this 
requirement to those who need to know. Enforcement will mean 
that press is turned away, as happened last year. The public 
has a legitimate interest in AIDS research, and is more 
likely to provide support if it can see the results.

The happenstance dynamics of one major and prestigious 
conference must not be allowed to establish a general pattern 
of dysfunctional impediments to the communication of AIDS 
research information.


***** Qigong Program on San Francisco KQED TV, Beginning 
December 7

A course in Qigong (a traditional Chinese therapeutic 
exercise) will be presented on public television in the San 
Francisco area, starting Saturday December 7, 6:00 a.m. to 
6:30 a.m. for four weeks. It will start again on January 4 
and repeat for another four weeks.

This course is also available on videotape through the Immune 
Enhancement Project in San Francisco, 800/835-6555; all 
proceeds from the sale of this tape are contributed to serve 
people with HIV. The course grew out of a Qigong class which 
meets twice a week in San Francisco; for information about 
this class, call Emilio Gonzalez, 415/255-0265, or George 
Wedemeyer, 415/661-2080.

Other public broadcasting stations wanting to broadcast this 
series can contact Qigong for Health, through the Immune 
Enhancement Project at the 800 number above.


***** AIDS TREATMENT NEWS
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   Internet: aidsnews@aidsnews.org
Editor and Publisher:
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Statement of Purpose:
AIDS TREATMENT NEWS reports on experimental and 
standard treatments, especially those available now. We 
interview physicians, scientists, other health 
professionals, and persons with AIDS or HIV; we also 
collect information from meetings and conferences, 
medical journals, and computer databases. Long-term 
survivors have usually tried many different treatments, 
and found combinations which work for them. AIDS 
Treatment News does not recommend particular 
therapies, but seeks to increase the options available.

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ISSN # 1052-4207 

Copyright 1996 by John S. James.  Permission granted for 
noncommercial reproduction, provided that our address 
and phone number are included if more than short 
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