From: Billi Goldberg <bigoldberg@igc.apc.org>
Subject: ATN #166
Note: Copyright 1992, Dan R. Greening. Non-commercial reproduction allowed.
Archive-Number: 6733
Organization: unspecified
Date: Thu, 7 Jan 93 20:37:15 PST

 AIDS TREATMENT NEWS Issue #166, January 1, 1993
   phone 800/TREAT-1-2, or 415/255-0588 
CONTENTS 
AIDS Treatments 1992/1993: 

Where Are We Now? 

1993 Nucleoside-Analog Trial Results Expected 

Shalala for HHS Secretary: Reaction Mostly Good 

Anabolic Steroids for Controlling Weight Loss: Australian Experience, 
U.S. Trial 

Report from the VIIth International Conference on AIDS in Africa 

Announcements:
   Alternative/Complementary Treatment Workshop U.S./Canada 
      Tour; Assistance Sought.

   Media, Public Relations Professionals: ACT UP Needs 
      Volunteer Help 

 ***** AIDS Treatments 1992/1993: Where Are We Now? 
by John S. James 

Each new year we write an overview of treatment development,  or a list 
of treatments to watch in the coming year. This  year's overview is 
difficult to write. Why? More is happening in AIDS treatment now than 
ever before; it  is harder than ever to keep up with the news. But 
almost all  of it is little news, better than nothing, but not centrally  
important for saving lives. Examples include FDA approval of  yet 
another marginal drug; more news on nucleoside trials that could never 
produce a decisive improvement; the latest  basic-research advance that, 
with luck, might be a practical  treatment in ten years; more 
"alternative" treatments with  nothing decisive to offer; another 
seminar on how to turn on  your immune system; or a new cure-all 
proposed (or old one recycled). 

What do all of these very different examples have in common?  Even when 
legitimate and necessary, they also represent the  kind of diversionary 
activity which occurs when there is no satisfactory way to address a 
major problem. When there are no alternatives, such substitute 
activities may be better than nothing. 

But what is disturbing today is that there are clear, meaningful, and 
widely accepted avenues for pursuing  potentially major AIDS treatment 
advances. But due to  mismanagement and disorganization (which stem, 
ultimately, from the lack of consistent national political will) they 
are  not being pursued with even a shadow of the seriousness they  
deserve. 

The extended example below shows what has happened with what  many 
scientists consider to be the most promising class of  AIDS drug being 
developed. As you read it, keep in mind that  every drug's story is 
different -- and that problems are  normal in drug development. The real 
issue is not that  problems occur, but that there is no effective effort 
to fix  them. And this issue is not unique to the example below, but  is 
common to almost every AIDS antiviral ever proposed or  tested.

Example: Tat Inhibitors 

For years leading AIDS scientists have believed that drugs to  inhibit 
the "tat" gene of HIV would be perhaps the single  most promising 
approach to developing better AIDS treatments.  This article will not 
list the many reasons for the  exceptional promise of this class of 
drugs (see "Tat Drug   Development: Current Status," in AIDS TREATMENT 
NEWS #153,  June 19, 1992). What most interests us is that almost all 
the  antivirals now in use or being tested (including AZT, ddI,  ddC, 
and d4T) can only help to prevent HIV infection of new  cells, but have 
no effect on the virus in chronically   infected cells, leaving a 
reservoir which can produce illness  in various ways, as well as 
creating drug-resistant virus. In  contrast, an effective tat inhibitor 
would shut down all HIV  activity, even in already-infected cells. 

Tat inhibitors should be fairly easy to discover, because an  efficient 
screening test for finding them is readily  available. In fact, the 
fastest and least expensive approach  to developing a tat drug might 
well be to screen the thousands of drugs and others substances already 
in human  use; if a good tat inhibitor is found, then all the safety,  
pharmacology, manufacturing, etc. problems will have already  been 
worked out, and the drug would be ready for use. No one  is doing such 
screening, however, since there is no  commercial incentive. 

Instead, the whole pharmaceutical industry (or rather, that  small part 
of it which has any interest in AIDS) seems to be  waiting to see what 
happens with the only tat inhibitor drug  now in human testing -- 
code-named Ro-24-7429, being  developed by Hoffmann-La Roche. Meanwhile, 
governments (and  the rest of the AIDS world) wait for industry to 
develop tat  drugs. In the middle of a major worldwide epidemic, the 
most  promising approach to treatment development has been  abandoned to 
a single project with a single drug in a single   company. The problem 
is that the whole world waits for what  might be the wrong tat drug, and 
almost certainly is the  wrong company. 

Ro-24-7429 has been delayed because its complex and unusual  
pharmacology required additional studies to learn how to  safely 
administer it. But the biggest problem has been the  lack of commitment 
by Roche to the project. First, the  company decided to abandon the 
drug, calling off an imminent  human trial at Johns Hopkins University 
by a phone call to  the researchers there on April 29, 1991. After AIDS  
scientists expressed great concern over the loss of the only  tat 
inhibitor in development (see "Promising AIDS Drug  Looking for a 
Sponsor," Science, July 19, 1991, pages 262- 263; also see the Wall 
Street Journal, May 30, 1991, page  B4), Roche decided to sell 
Ro-24-7429 instead of abandoning  it. It came within days of selling it 
(to Burroughs- Wellcome), but then changed its mind again and decided to  
develop the drug itself. 

A major problem now seems to be the lack of commitment of  enough staff 
and resources to this drug within the company.  Trials have repeatedly 
been delayed, and there is still no  data on whether or not the drug 
reduces viral load in people,  despite the fact that human testing began 
well over a year   ago. 

Within Roche, two people are in charge of the tat inhibitor  
development; we do not know if there is any other  professional staff on 
the project. During a conference call  last month, we asked these two 
about an earlier attempt to   develop a tat drug, which had apparently 
failed. At least as  far back as 1988, German scientists had proposed 
that d- penicillamine, a prescription drug, might be a useful tat  
inhibitor; an article published in 1986 described a test of  the drug as 
an HIV treatment in Germany. A later study,  however, (presented in June 
1990 at the Sixth International  Conference on AIDS in San Francisco) 
reported harmful side   effects and no evidence of benefit. We wondered 
what lessons  had been learned from this apparent failure, and how they  
were being incorporated into future tat-drug development. But  it turned 
out that the team developing Ro-24-7429 at Roche  did not even know that 
d-penicillamine had been proposed or  tested as a tat inhibitor, despite 
several published papers  on the earlier work -- well over a year after 
Roche had its  own tat inhibitor in people. 

This is the project that the whole world has entrusted, for  two years, 
as the sole human developer of the most promising  class of potential 
AIDS drugs, the most feasible development  path for finding more 
effective treatments. 

Fortunately the AIDS Clinical Trials Group (ACTG) of the U.S.  National 
Institute of Allergy and Infectious Diseases (NIAID)  began a trial of 
Ro-24-7429 in December, 1992. This trial  will, for the first time, 
measure indicators of viral  activity before and after treatment, so 
that at last we will  know whether or not the drug has biological 
activity in  people. Our main misgiving now is that Roche has so little  
interest in its own drug. What might it know that we don't?  And if this 
drug should fail, will there be a stampede to  reject the whole class of 
drugs even if there is no rational  reason to do so? 

Why would Roche decide not to sell its drug after all, if it  had so 
little commitment to it? Since we cannot read minds,  we can only guess 
at possible scenarios. If tat inhibitors  are indeed promising but 
Ro-24-7429 had problems that would  delay or rule out its final 
development and marketing, then  Roche would stand to lose its valuable 
lead in tat drugs if  another company entered the field with a better 
one. The best  way to prevent that would be to avoid releasing the key 
data  on the drug -- whether it has biological activity in humans  -- 
since other companies would then be likely avoid risk by  waiting to see 
what happened with Ro-24-7429 before  committing themselves to tat drugs 
-- giving Roche time to  either overcome the problems with Ro-24-7429, 
or to find a  second-generation drug to replace it. 

Another speculation is that if there were anything  embarrassing in the 
history of the tat drug project, Roche  might not have wanted the 
evidence to go out its door and  beyond its control. 

Tat inhibitors appear to be much easier to develop than other  classes 
of drugs such as protease (proteinase) inhibitors.  But the latter have 
received much more attention, with  several companies competing to 
develop them -- probably   because protease inhibitors present more 
professionally  interesting challenges. With tat drugs, enough 
fundamental  problems have already been solved that what is needed now 
is  a straightforward, well-managed development effort. But  scientists 
are attracted to scientific not management  problems, and non-scientists 
have not understood the drug.  And no one has had the national or 
international mandate to  see that a first-class opportunity was being 
wasted, or the  authority to do anything about it. 

The issue here is not Roche, but the rest of the world. How  can the 
United States (which does the most biomedical AIDS  research), or any 
other country, allow its vital interest in  better AIDS treatment to 
remain so unguarded and unattended?

Comment: Where Do We Go From Here? 

We believe that the most important AIDS treatment development  in 1992 
was the election of Bill Clinton instead of George  Bush as U.S. 
president. But maybe not for the reasons people  think.

At AIDS TREATMENT NEWS we spend considerable time on the  phone talking 
to people whose primary work is not AIDS --  mainstream reporters and 
corporate officials, for example.  Already since the election there 
seems to be a difference in  seriousness, in respect for the issues. The 
difference seems  to go beyond AIDS, to reflect a national change toward  
dealing with public problems, instead of finding clever  maneuvers to 
excuse an evasion of responsibility. 

But the hostile Reagan-Bush administration also provided an  excuse for 
the AIDS community. With leaders like those, we  were free to defend 
against the latest attacks as they  occurred, without responsibility for 
setting our own agenda  or for getting results. For example, Bush never 
received a  consensus demand from the AIDS community for improvements in  
treatment research, except for faster access to treatments  nearing 
approval (which he supported), and for more money  (where he was not the 
leading obstacle). 

Maybe our lack of input made no difference anyway; the White  House 
overruled the entire AIDS community, as well as the  intent of Congress, 
on the HIV travel-immigration ban,  apparently as a political payoff to 
bigots. But in the future, with a potentially responsive government, it 
will be  disastrous if the AIDS community does not formulate workable  
research policies and make them known. 

The biggest problem in research is the lack of a consistent  national 
commitment to save lives. Researchers have not had  the support they 
need to do what they know is important. So  trials have focused on 
commercial drugs -- known to be  inadequate, but where the money is -- 
while clear prospects  for decisive treatment advances have remained 
ignored or  grossly under emphasized. And basic research has focused on  
high-tech, commercially viable toys with little regard for  what could 
or could not be used in the foreseeable future. 

Covering the News 

When reading AIDS TREATMENT NEWSletters in 1993 and beyond,  remember 
that we have to cover two kinds of news: what  happens, and what doesn't 
happen. In AIDS treatment  development, the latter has been by far the 
more important.   (The mainstream press need only cover the former, 
however,  since it is in the entertainment business and not responsible  
for conveying information that citizens could use.) 

We, too, must spend most of our space on mediocre news --  about the 
marginal nucleoside analog, antibiotic, drug  combination, or 
"alternative" treatment -- because usually  that is all there is. And as 
the standard of care changes,   there may be disruptive ripples through 
ongoing clinical  trials, which were not designed with the real world in 
mind.  We will cover the ethical debates, the endless meetings, the  
marching in place of hundreds of well-paid professionals  going nowhere. 
But we should also remember that, with a potentially friendly  
government for the first time in the AIDS epidemic, it is  more 
important than ever before to occasionally step back  from the ritual of 
the moment to consider what is truly important for saving lives, and 
what is not. There is no  longer any excuse for a no-win war in AIDS 
treatment  development. No one can guarantee a date when a better  
treatment might be found. But we can insist that the obvious  good leads 
in front of us be promptly followed up. 

 ***** 1993 Nucleoside-Analog Trial Results Expected 
By Larry Tate 

The past year has seen significant developments in the area  of basic 
nucleoside analog antiretrovirals -- AZT, ddC, ddI,  and d4T. DDC was 
finally approved, for combination use; ddI's  approved indication was 
expanded, and promising data on  combination use with AZT was revealed; 
d4T began a parallel- track program; and a European-Australian study 
supported the  use of AZT by people with T-helper counts up to 750. The  
coming year will bring further developments for these drugs  and 
combinations of them, as well as for 3TC, another  nucleoside analog, 
and a three-drug combination of AZT, ddC,  and alpha interferon. 
It is rarely possible to say exactly when data from specific  trials 
will be made public; the timelines mentioned below can  only be 
approximate. 

The first key development in 1993 will be the long-awaited  release of 
data from ACTG 116A, a study comparing AZT to ddI  in people with fewer 
than four months' prior AZT use. This  amounts to comparing the two 
drugs as first-line therapy --  and suggesting which drug patients 
starting anti-HIV therapy   should use. By mid-January, it should be 
known whether ddI in  this circumstance is more effective, less 
effective, or about  the same as AZT. The study group had T-helper 
counts under  300, but the results might well apply to people starting  
treatment at all T-helper levels. 

AZT has so far been the standard first-line therapy; should  this study 
prove it to be less effective than ddI, there  would be a major 
reassessment of how these drugs are used,  affecting not only clinical 
practice but probably some   ongoing trials as well. If the two drugs 
show equivalent  efficacy, or if AZT is more effective than ddI, the 
current  standard of care may not be much altered. 

Also long-awaited are the results of ACTG 019, a large and  very 
long-running trial that compared AZT to placebo in  people who started 
with a wide range of T-helper counts --  about half of them over 500. 
Data on the group who started with counts over 500 should provide the 
clearest answer from  any U.S. study on the value of AZT (and, by 
implication,  other nucleosides) in people in early stages of infection. 
If  AZT delays disease progression in this group, there could for  the 
first time be an FDA-approved therapy for people with T- helper counts 
over 500. Data from ACTG 019 may be available  as early as February, or 
if not, by mid-year. 

The comparable and equally long-running Concorde study in  Europe also 
looks at AZT versus placebo in people starting  with a wide range of 
T-helper counts. Data from the Concorde  study also may be available 
early in the year, or by mid- year.

By late spring, final data is expected from ACTG 155, a study  which 
compared AZT to a combination of AZT and ddC in people  with fewer than 
200 T-helper cells. The FDA, on the basis of  two smaller studies, 
approved ddC for combination use with  AZT, but the data from ACTG 155 
will be critical in   confirming the value of combination therapy. If 
the results  show an advantage for the combination, the current label  
indications for AZT/ddC use (which are widely considered to  be somewhat 
tentative and confusing) may be clarified and strengthened by the FDA.  
At the 1992 International AIDS Conference, three small  studies reported 
interim data on combinations of AZT and ddI.  All three have been 
completed or are near completion, and are  likely to publish final data 
in the first half of the year.  These studies used different doses and 
entry criteria and   monotherapy control groups, making it difficult to 
compare  results; however, should final data indicate an across-the- 
board advantage for combining AZT and ddI, there would then  be at least 
as much data on the AZT/ddI combination as there  was on the AZT/ddC 
combination when the FDA approved ddC. A  change in clinical practice 
and in FDA indications might  result. 

(It should be noted that ACTG 175, the large trial comparing  
combinations of AZT/ddI and AZT/ddC to AZT and ddI as single  agents, is 
not expected to make public any results in 1993.) 
The ongoing d4T trials are not expected to announce any  results this 
year. At least one pilot study combining d4T  with ddI is planned; 
others may follow. 

Only one nucleoside in early trials appears to be moving  smoothly 
toward wider use. 3TC is now in late dose-ranging  studies, and is 
expected to start large Phase II comparative  studies in the spring 
(similar in some ways to the d4T trials  now in progress). Sources have 
told us that this drug has so  far shown clear anti-HIV activity and no 
serious side  effects. It could be speculated that, when these Phase II  
trials start, there might also be a role for a 3TC expanded- access 
program, but it is too soon to know. 

Finally, two studies comparing the combination of AZT and ddC  to a 
three-drug combination of AZT, ddC, and alpha interferon  will be 
continuing through the year. Late in the year, some  interim data might 
be available from the larger of these  studies, looking at people with 
T-helper counts between 300  and 500. Obviously, there are a number of 
possibilities for  studies of various three-drug combinations, and 
results from  this trial could stimulate that research. 

Comment 

Nucleoside analogs are often discounted by people who argue,  
incontestably, that there are stringent limits to what these  drugs can 
do and that their various side effects often cause  great problems to 
patients. Nucleosides have always been  regarded as a stopgap until 
better treatments arrive. 

That may be true, but there is a fairly clear understanding  of how they 
work and how their side effects can sometimes be  managed; three are 
FDA-approved and two more may be on the  way to approval; and they are 
backed by big drug companies  with the resources to develop them 
quickly. Although  nucleosides are of limited efficacy, those limits may 
not  turn out to be so stringent as was once thought, if up to  five 
drugs come to be used serially and in combinations.  Therefore, any new 
availability of nucleosides or new   information on how to use them is 
important. 

 ***** Shalala For HHS Secretary: Reaction Mostly Good 
by Keith Griffith 

The announcement that Dr. Donna Shalala will serve as Cabinet  Secretary 
of Health and Human Services (HHS) for President- elect Bill Clinton is 
viewed favorably by most persons with  whom AIDS TREATMENT NEWS has 
spoken. Most believe Dr. Shalala  would bring excellent managerial 
skills to the job, but  almost everyone who has observed her performance 
at  University of Wisconsin-Madison said there were controversies   in 
her record that might indicate a need for caution.  

Dr. Shalala will oversee agencies that account for 40 percent  of all 
federal spending including the National Institutes of  Health, the Food 
and Drug Administration, and the Centers for  Disease Control and 
Prevention. Additionally, she must deal  with entitlement programs such 
as Social Security, Medicare,  and Medicaid which appear to be headed 
for major changes in  an effort by Clinton to address the federal 
deficit. Dr.  Shalala, in remarks delivered at the news conference to  
announce her appointment, included AIDS as one of the top  five 
priorities in her first year. She has so far not   elaborated on what 
that might mean, and requests from AIDS  TREATMENT NEWS for an interview 
were denied. This article is  based on interviews with AIDS policy 
specialists in  Washington, community leaders and university officials 
in   Madison, and a close study of numerous interviews given in  recent 
years by Dr. Shalala.  

Background 

In her role as chancellor at University of Wisconsin-Madison,  a job she 
took in 1988, Dr. Shalala (pronounced shuh-LAY-luh)  has been in charge 
of the nation's sixth largest university  and the largest public 
research university in the country.  Previous to the chancellorship, she 
was president of Hunter   College in New York and an assistant secretary 
in the  Department of Housing and Urban Development under President  
Carter. Her first major exposure to public service was on the  Municipal 
Assistance Corporation, the agency that was created  to return New York 
to financial solvency in the mid- seventies. People use terms like 
"crackerjack administrator"  and "perfectionist" in describing her 
management style.  

Dr. Shalala has little experience in public health, and with  AIDS in 
particular. AIDS TREATMENT NEWS has found few hints  of her likely 
positions regarding treatment research, access  to care, and other 
critical AIDS issues. Dr. Shalala is  credited with filling some key 
positions at the university   with persons who have experience in the 
field of AIDS.  Additionally, Mary Alice Mowry, executive director of 
Madison  AIDS Support Network, the primary AIDS agency in Madison,  
applauded Dr. Shalala for using her influence to bring key  people into 
the struggle against AIDS who had previously been  hesitant. 
Past Controversy  

The primary concern we heard was that Dr. Shalala would not  "stick her 
neck out for us," as one activist stated it. Dr.  Shalala has faced the 
condemnation of protesters because of a  belief among some in Madison 
that she was not acting entirely  responsibly on behalf of vulnerable 
groups including people   living with AIDS. Members of one senior class 
wore latex  gloves to accept their diplomas from Dr. Shalala in protest  
over her silence regarding one particular incident. At a  protest over 
the presence of ROTC on campus (ROTC, like all  U.S. military programs, 
does not allow recruitment of gay men  and lesbians, and numerous 
college campuses have removed the  program in recent years), several 
persons engaged in civil  disobedience were removed by campus police who 
were wearing  latex gloves, a signal many interpreted as supporting 
irrational fears of persons who might have AIDS.  

Activists claim Dr. Shalala failed to provide leadership,  instead 
choosing silence. Perhaps more importantly, many we  spoke with fear 
this incident, and several others which were  not AIDS-related, may 
indicate an unwillingness to   aggressively speak out if it is too 
politically sensitive. "I  never heard a word from her on the issue. She 
did not condemn  the protesters, but she also didn't condemn police 
behavior,"  remembers Maria Hanson, Outreach Coordinator for a Madison  
group, United, and one of those arrested. This issue (ROTC is   still on 
campus) is considered by many to be one of the low  points of Dr. 
Shalala's stay in Madison. "I think she played  politics regarding 
ROTC," stated Mowry. "It was one of the  things she could have done 
better." 

Management Skills 

In spite of concerns from some that Dr. Shalala might not be  willing to 
use her political capital on a controversial issue  such as AIDS, most 
people we spoke with expect her to bring  positive administrative change 
to HHS. "Clearly she has not  had a lot of experience on AIDS issues," 
stated Jeff Levi,   Director of Government Affairs at AIDS Action 
Council. "It is  the frame of mind she brings to the job that is 
important."  Her management skills and theories appear to be why Clinton  
appointed her. In remarks at the recent Economic Conference  in Little 
Rock, Dr. Shalala referred to "the myth that   complex bureaucracies 
can't improve."  

In one analysis she is described as someone who will "call on  a 
management style that has served her well in federal  government, city 
politics and academia: She targets a problem  precisely, aims carefully 
and then attacks it from several  angles at once -- verbally, publicly, 
forcefully."1 This may  be good news for persons who have pleaded for 
forceful  leadership on AIDS. Additionally, Dr. Shalala told one  
interviewer, "I would say that I have essentially the skills  of skilled 
managers and that means I am strategic. If you  look at corporate 
executives in this country who are  successful, they are strategic 
thinkers...My ability [is] to  put all of the pieces together in an 
overall strategy."2 Jane  Silver, Director of Public Policy for AmFAR, 
agrees that this  is exactly what is needed. "Dr. Shalala needs to 
develop a  national plan, implement it and continue identifying AIDS to  
the public as the important health issue it is." Silver  believes it is 
a very good sign that AIDS has already been  identified by the 
Secretary-designate as a top priority. 

 Dr. Shalala has spoken about other issues of concern to the  AIDS 
community, although not in the context of AIDS: The need  to address 
greed, waste and duplication in spending federal  money, especially in 
universities; the ongoing problem of  scientific research fraud; and a 
strong desire for federal   government to recognize that research and 
development in  basic sciences must continue to grow even in a time of  
deficits.  

Comment 

Perhaps the biggest uncertainty right now is how strong a  mandate 
President-elect Clinton will provide his cabinet  appointee to HHS. Many 
we spoke with who have observed Dr.  Shalala say she is far too much of 
an "insider" to stand firm  on controversies that Clinton would rather 
ignore. Maria  Hanson, who has been monitoring Dr. Shalala on numerous  
issues in Madison, urges that people "not let down their  guard just 
because there may be a less hostile secretary  overseeing HHS. Unless 
Dr. Shalala has a lot of people in the  roles of watchdog, she may not 
order priorities where they  need to be." No matter how progressive 
Clinton may look  compared to his predecessors, there will be much that 
the  AIDS community feels is essential that will not fit into his  
agenda. Whether Dr. Shalala will be an advocate for people  living with 
HIV or someone who only carries out White House  policy is a critical 
determination yet to be made.  

References 

1. Cleveland C. (campus CEO at the University of Wisconsin).  Working 
Woman, December 1991; pages 60-63. 
2. Bernstein A, Mow S. On Changing Academic Culture From the  Inside. 
Change, January/February 1989; pages 20-29. 

 ***** Anabolic Steroids for Controlling Weight Loss: 
      Australian Experience, U.S. Trial

by John S. James 

Anabolic steroids are best known to the public through the  bad press 
resulting from non-medical use by athletes for  muscle building in 
competitive sports. Unfortunately the  resulting controversy has held 
back legitimate medical   research and use of these important drugs. 
(Anabolic steroids  should not be confused with corticosteroids, which 
have  entirely different effects.) 

Recently we called Julian Gold, M.D., at the Albion Street  (AIDS) 
Centre, the major AIDS medical facility in Sydney,  Australia, about an 
unrelated subject (a dose and toxicity  study of hypericin, an 
antiviral). Dr. Gold also told us about the Centre's experience with a 
trial of low-dose  nandrolone decanoate (Deca-Durabolin), an anabolic 
steroid,  for preventing further loss of body weight which has no  
obvious cause. 

We interviewed Dr. Gold, and also called Donald Kotler, M.D.,  a leading 
specialist in gastroenterological complications of  AIDS, who is now 
conducting a trial of a different but  related anabolic steroid in New 
York. 

Interview with Julian Gold, M.D.

ATN: What patients are you treating with nandrolone decanoate   (Deca-
Durabolin)?

JG: We started to use this drug two years ago, at first with  patients 
at very late stages of HIV infection, who had lost  considerable body 
weight, 15 to 20 percent or more. We  treated over 30 patients with the 
injectable Deca Durabolin,  using 50 to 100 mg per week. This was not 
very useful, as  after nine months the weight loss continued. 
In the last year, we have started instead to treat people who  have lost 
between five and ten percent of body weight. We are  now using a dose of 
100 mg every two weeks. 

ATN: So it's just one shot every two weeks? 

JG: That's right. We have had about 50 people who have used  this 
regimen. The objective is to stabilize weight loss,  rather than to have 
these people put on large amounts of  weight -- not to try to replace, 
because these patients have not lost too much weight. And for this study 
we chose people  who can still eat, and preferably can still get at 
least  minimal exercise, including walking or perhaps they can still  go 
to the gym. We tried to pick people who were just on the  precipice, 
where if nothing were done they would lose a lot  of weight. 
We looked for patients on an adequate and nutritious diet but  who still 
continue to lose weight. They need to have dietary  counseling first, 
before entering the study, to be sure it is  not a bad diet that is 
causing the problem. And they must not  have any obvious cause of the 
weight loss, such as gastrointestinal infections, malabsorption, or 
untreatable  diarrhea. 

ATN: Who should not use the drug for safety reasons? 

JG: Underlying diabetes or other endocrine problems, or liver  disease, 
would be among the contraindications. But we have  now monitored almost 
a hundred people taking this drug, and  we found no adverse effects on 
liver functions or any of the  blood biochemistry; in fact it has 
improved hemoglobin in  some people. We found no adverse effect on HIV 
antigen or T- helper counts. 

ATN: How long have patients been on the new regimen so far. 

JG: For 12 months. 

ATN: Are any women using it?

JG: Deca-Durabolin is a testosterone derivative, which could  cause 
problems for women. We have not used it in women, but  possibly we may 
try in the future. We are doing this step by  step. 
ATN: Do you have industry support? 

JG: Our research is sponsored by Organon, a local branch of  Akzo, which 
is headquartered in the Netherlands. Akzo makes  the drug available to 
us. 
ATN: What are your future plans? 

JG: First, we are analyzing our existing data for  publication. 
So far we have only conducted a pilot study, looking at any  toxicity or 
problems. Now we are planning a more structured  clinical trial, to give 
selected people the drug for 26 weeks  and monitor more test results 
than before, including  different measures of body composition. Then we 
will move   into a comparative study, possibly comparing this drug with  
one of the other weight-loss treatments. 

The politics of AIDS, together with the politics of anabolic  steroids, 
has meant that we have to go slowly. But we are  optimistic; people on 
the treatment feel better, their  appetite improves, and we have not 
noticed the potential  problems like virilizing [masculinizing] effects 
and  excessive muscle gain, because we do not use a high dose.

ATN: Can people contact you for more information? 

JG: They can contact the Albion Street (AIDS) Centre, in  Sydney; phone 
61-2-332-1090, fax 332-4219. They can ask for  Chris Oliver our clinical 
nutritionist, or ask for me. 

 Oxandrolone Trial in New York: Interview with Donald Kotler,  M.D. 
To get another perspective on the use of anabolic steroids in  AIDS, we 
spoke briefly with Donald P. Kotler, M.D., at St.  Luke's/Roosevelt 
Hospital Center in New York, who is  currently running a trial of 
another anabolic steroid,   oxandrolone, and is familiar with the work 
in Australia. 

ATN: How does oxandrolone differ from the nandrolone  decanoate which is 
being used in Australia? 

DK: Both are testosterone derivatives; they differ in  strength. 
Testosterone has both anabolic and androgenic  (masculinizing) effects. 
Because of the androgenic  properties, both are largely ruled out in 
women. Other drugs  which have the anabolic effect without the strong 
androgenic  effect might be more suitable for women. 

ATN: Why are anabolic steroids being tried for treating HIV? 

DK: This treatment is supported by a good theory. But does  the theory 
work? That is what the trials are designed to find  out. 

We know that there are metabolic changes in some AIDS  patients that 
keep the body from holding onto proteins.  Anabolics help the body hold 
onto proteins. But will they  actually benefit patients? That needs to 
be shown. 

Our trial compares two doses of oxandrolone to a placebo. We  are 
recruiting 24 patients for the four-month trial; the 7th  started today. 
Only one has finished so far.

We have seen no side effects at all from the treatment, and  some weight 
gain. We are still waiting for body-composition  measurements. 

ATN: Do physicians have trouble prescribing these drugs  because of the 
controversy around them? 

DK: These are controlled drugs in the U.S.; a triplicate  prescription 
is required. There is abuse potential, with  danger to the liver from 
the high doses sometimes used by  bodybuilders.

ATN: So physicians may be reluctant to prescribe these drugs,  without a 
clear consensus for their use. 

DK: We are pushing to get the data as soon as possible. The  question 
is, will the experience fit the theory. 

Note to potential volunteers: Dr. Kotler's trial in New York  is testing 
two doses of oxandrolone for the treatment of  malnutrition associated 
with HIV infection. One third of the  volunteers will receive a placebo. 
The trial lasts for four  months, and followup treatment will be made 
available. This  trial is sponsored by Gynex Pharmaceuticals, Inc., of 
Vernon  Hills, Illinois. 

The study includes nutritional assessments, and measurements  of food 
intake, muscle strength, quality of life, and immune  function. There is 
no cost to the volunteers. 

If you believe that you are suffering from malnutrition as a  result of 
HIV infection and are interested in volunteering  for this trial, please 
call Jodi in Dr. Kotler's office,  212/523-3670. 

 Oxandrolone Trial for Muscle Weakness: Miami, Chapel Hill,  New York 
A separate but related trial of the same drug for a different  use is 
also being conducted by Gynex Pharmaceuticals. "A  Phase II Double Blind 
Placebo Controlled Study of Oxandrolone  for HIV-Associated 
Myopathy/Muscle Weakness" is seeking HIV- positive men 18 or older with 
generalized or proximal muscle  weakness. Antiretroviral treatment is 
not required, but  patients on any FDA-approved antiretroviral must have 
been on  the drug for at least eight weeks before enrollment. There  are 
several other entry criteria, mostly for assuring patient  safety. 
This trial is being conducted at three sites: the University  of Miami 
School of Medicine, Miami; the University of North  Carolina, Chapel 
Hill; and Mt. Sinai School of Medicine, New  York. Twenty three 
volunteers are already enrolled, of the  total target enrollment of 48. 
Oxandrolone is already an approved drug. If these trials are  
successful, the company will obtain FDA approval to market it  for the 
AIDS-related uses which are now being tested. 

 ***** VIIth International Conference on AIDS in Africa 
By Jason Heyman 

For only the third time in its history, the VIIth  International 
Conference on AIDS in Africa took place in an  African city, Yaounde, 
Cameroon, from December 8-11, 1992.  Previously, the conference has been 
held in Europe with   sponsorship from European and Canadian health 
organizations  including the World Health Organization. Two reporters 
from  AIDS TREATMENT NEWS (this writer and Nancy Solomon) attended  in 
order to learn about international treatment issues.  However, little 
treatment information was presented.  

The conference took place in what felt like an atmosphere of  failure. 
Prevention, which was the main topic, has been  failing to stop the 
rapid spread of HIV in Africa. According  to Michael Merson, the 
director of the World Health  Organization's Global Program on AIDS, 
"There have already  been over 7.5 million infections in adults [in 
Africa] since  the start of the pandemic, close to 4 million of them in  
women." 

A different AIDS virus, HIV-2, was discussed in detail at the  
conference. HIV-2 has come to be known as the virus of  developing 
countries and has not been given the attention  that HIV-1 has received. 
One interesting difference is that  HIV-2 is much less likely to be 
transmitted from mother to  child. 

Prevention vs. Treatment 

At a symposium held during the conference by The Wellcome  Foundation, 
prominent African community activists expressed  frustration at the 
failure of current efforts to stop the  spread of AIDS. One of the most 
inspiring speeches was  delivered by Sy El Hadj Amadou, the African 
Secretary of the   International Council of AIDS Service Organizations 
(ICASO),  who drew a connection between the failure of prevention  
efforts and the lack of AIDS treatments available to  Africans.  
He explained that as a result of the African AIDS community's  defeatist 
attitude towards access to treatment, and the  West's view of Africa as 
a lost cause, all anti-AIDS efforts  are seen as half-hearted and are 
not taken seriously by the  public. Prevention tactics, he explained, 
must be based on a re-affirmation of life and the promise of hope. Such 
efforts  are doomed to fail in this climate of neglect. "How can we be  
credible in this field if we adopt this defeatist attitude,  by 
accepting in advance that even if there is an efficient  drug against 
this disease, the population that we want to   educate to change their 
behavior won't have access to this  medication." 

"The fight for better access of the African population to  
treatment.....is the only way that we will overcome the  problems 
created by poverty and lack of resources. Through  this we will create a 
credible education program, and we will  make our message obtainable and 
support the population to  change their attitude." (Translated from the 
French, by the  official conference translator).  

John Ziegler, M.D., from the University of California San  Francisco 
Medical Center, spoke on, "The Management of HIV  Infection," which 
included an "Introduction to  Antiretrovirals." To an American observer 
it seemed as if he were going back in time to the introduction of AZT, 
but AIDS  treatment in Africa with pharmaceutical products is almost  
non-existent. Dr. Ziegler was in fact looking forward to a  time when 
basic antiretroviral therapies will be available.  "In anticipation of 
more effective and cheaper drugs in the  near future, studies should 
commence in selected centers to  define a clinical role for 
antiretroviral therapy in Africa." 

At the end of the Wellcome symposium one questioner asked if  he could 
direct a question to Wellcome itself. He asked what  they are doing to 
make Burroughs Wellcome drugs, specifically  AZT and acyclovir, 
available in Africa. With some hesitation  a Wellcome employee explained 
that he was not at liberty to  give that information, but that we should 
rest assured they  are working on it. 

The only treatment discussed at any length at the conference  was PCM-4, 
a little-known alternative treatment made from  extracts of pig spleen 
and Siberian genseng, Eleutherococcus  senticosus; it is being studied 
in the United States and in  Uganda, and is sold in buyers' clubs and 
health-food stores. 

The U.S. Agency for International Development (USAID), which  controls 
all government money spent on AIDS in developing  countries, even has 
legal guidelines that restrict money to  prevention uses only. A USAID 
representative, Gordon Murchie,  explained that they do support research 
efforts abroad, but  to take on the issue of treatment "would be a vast   
undertaking, comparable to taking over the health care  systems of all 
the countries concerned." 

 The World Health Organization is the only international  organization 
that is currently distributing drugs for the  treatment of AIDS, but 
according to recent rumors their  Essential Drug Program has recently 
cut its AIDS drugs for lack of funds. Some of the drugs available 
through this  program are as basic as acetaminophen and petroleum jelly.  
African Traditional Medicine 

Traditional African medical practitioners were largely absent  at this 
conference. Speakers such as Susan Anderson from the  World Health 
Organization, who discussed community care,  spoke about the important 
role that traditional healers play  in the African health care system, 
but these practitioners  themselves had no presence on the podium. 
Most Africans go first to a traditional healer when they are  ill. This 
important link has been generally ignored by the  Western-oriented 
development agencies that are re-creating  African health care systems 
in the image of European and  American ones. With their direct access to 
the population,   traditional practitioners can have an important role 
in  education, prevention, and treatment. 

One traditional healer, Fokoundang Adam Usumanu, was present  at the 
conference, and was excited by the prospect of working  together with 
the formal health care system. Currently he is  trying to organize a 
group of approximately forty traditional  medical practitioners in 
Cameroon to pool their knowledge and  resources to help treat people 
with AIDS. 

One of the treatments he uses is yohimbine, which in the  United States 
is a prescription drug found in the bark of the  Corynanthe johimbe tree 
and used for treating impotence in  men. AIDS TREATMENT NEWS #159 
(September 18, 1992) reported  on the experiences of two people with HIV 
who had positive  results using yohimbine for the treatment of fatigue. 
This  coincidence suggests again that traditional healers have  
knowledge of useful treatments, many of which are unknown to  western 
pharmacists. Fokoundang Adam Usumanu has 30  treatments that he 
currently employs. 

Comment  

One hopeful sign is that African governments are beginning to  openly 
confront AIDS. The Organization of African Unity, for  the first time 
in its history, addressed AIDS in its  "Declaration on the AIDS Epidemic 
-- July 1992." Its   treatment goal: "By mid 1993, we will have adopted 
a rational  AIDS care plan, including essential drugs for HIV-related  
illnesses, and a rational plan for family-based or community  care and 
support of AIDS survivors, including orphans." 

At the closing ceremony, Jonathan Mann, M.D., announced the  creation of 
a new center at Harvard University for the study  of health and human 
rights. He underscored the connection  between these two fields, making 
the observation that around  the world it has become clear that those 
people with power  who have their rights generally have their health. 
The slow  pace with which Africans with AIDS are being given access to  
treatment is an example of this. 

Although many people in the United States are frustrated by  the lack of 
effective treatments for many AIDS-related  conditions, we should follow 
the advice of Sy El Hadj Amadou  and make the treatments that we 
currently have available to  all those who need them. One panelist 
remarked that the   difficulty of getting AIDS treatments to all 
Africans who  need it can be put into perspective when we realize that 
many  cannot even get clean water. Still, we should make the effort  
instead of taking the defeatist attitude of powerful groups  like USAID. 
The success stories that exist offer hope that progress can  be made to 
stop the spread of HIV and treat those that are  already infected. The 
Know AIDS Society, in Nairobi, Kenya  was started by Joe Muriithi, who 
is one of the first Africans  to be open publicly about his HIV-status, 
and his wife Jane   Muriithi. Their work educating their community, with 
a  special focus on women, is an example of the success some  small 
groups have had, an example for the large development  agencies about 
what can work in Africa. And the skills and   knowledge of traditional 
African healers should not be  ignored. 

The effective work of small African grassroots organizations  like the 
Know AIDS Society, and of activists like Sy El Hadj  Amadou, shows that 
improvements can be made. 

 ***** Announcements

** Alternative/Complementary Treatment Workshop U.S./Canada 
   Tour; Help Sought 

"Staying Healthy with HIV," a well-regarded nonprofit  workshop in 
alternative/complementary/traditional treatments  for AIDS or HIV, is 
planning a tour of 25 cities in the U.S.  and Canada during March, 
April, and May 1993. At this time  the organizers are seeking help from 
local contacts in making   arrangements for the workshops, which they 
hope to provide  free.

Staying Healthy with HIV has been developed during the last  two years 
by David Baker, R.N., who specializes in teaching  health promotion to 
people with HIV, and Richard Copeland,  managing director of the Healing 
Alternatives Foundation (the  AIDS buyers' club in San Francisco) for 
almost four years.  The workshop has been presented twice through the 
San  Francisco Kaiser Medical Center, twice through the Sonoma  County 
Public Health Department, at the AIDS, Medicine, and  Miracles 
conference in Boulder, June 1992, and in San  Francisco at the Immune 
Enhancement Program and the Quan Yin  Healing Arts Center. Baker and 
Copeland presented a related  poster at the VIII International 
Conference on AIDS in  Amsterdam, July 19-24, 1992 ("Collected Research 
Findings and   Anecdotal Reports on the Optimal Dosage, Side Effects and  
Benefits of Selected Alternative Medications in Gay Men with  HIV," 
abstract #PoB3391). Their workshop is a project of the  Center for 
Natural and Traditional Medicines in Washington,  D.C. 

The workshop consists of a two to three hour session focusing  on 
alternative medications, together with discussions of  nutrition, stress 
management, understanding laboratory test  results, prophylaxis for 
opportunistic infections, and  holistic healing. Over 25 alternative 
treatments are   discussed in the 32-page handout given to participants. 
The  organizers do not recommend any particular treatments, but  provide 
information and guidelines to help evaluate different  options. (There 
is also a one-day version of the workshop,  limited to 10 people, which 
includes experiential exercises.) 

If you could help to bring Staying Healthy with HIV to your  city, 
contact the organizers at the address or phone below.  They need 
assistance in finding a free or low-cost facility,  publicity (including 
outreach to underserved communities),  arranging computer/modem access 
during their stay, finding a   host who can provide lodging and some 
meals, learning about  specific needs of your community, and locating 
additional  funding. 

If you could help, or want further information, contact David  Baker & 
Richard Copeland, Staying Healthy with HIV, 13-B  Belcher Street, San 
Francisco, CA 94114, 415/255-0690. 

** Media, Public Relations Professionals: ACT UP Needs 
   Volunteer Help 

The acyclovir price-cap issue (reported in AIDS TREATMENT  NEWS #165) 
shows the need for professional assistance to help  treatment activists 
advocate for the interests of the AIDS  community. ACT UP/Golden Gate, 
Project Inform, and AIDS Action Baltimore, although kept in the dark 
about details of  the Burroughs-Wellcome program, were able to reply 
with a  faxed press release on the same day the program was  announced. 
But only one mainstream newspaper (the San  Francisco Examiner) used the 
activists' information; the Wall  Street Journal covered only the 
Burroughs-Wellcome view. Most  of the press ignored the story entirely 
-- despite the fact  the issue of pharmaceutical prices is central to 
President- elect Clinton's effort to control health-care costs, and will  
probably be a major battle in Congress during the coming  year; a bill 
to discourage pharmaceutical price increases is  being sponsored by 
Senator David Pryor (Democrat, Arkansas). 

Activists can do the footwork -- writing, word processing,  faxing or 
mailing. But they need professional advice on  getting information into 
the media -- for example, on  building their lists of key people to send 
it to. They also  need strategic advice, for example in evaluating what 
stories  will or will not work even before negotiations begin with  
pharmaceutical companies, government officials, or others. 

In San Francisco, ACT UP/Golden Gate is seeking media  assistance now; 
if you can help, call Virg at 415/648-2758 or  Mark at 415/863-8797. In 
other areas, local treatment or  other AIDS organizations may also be 
able to use assistance. 

***** AIDS TREATMENT NEWS
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   John S. James
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ISSN # 1052-4207  

Copyright 1993 by John S. James.  Permission granted for  noncommercial 
reproduction, provided that our address  and phone number are included 
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