1994 Outlook

Much is happening in AIDS treatment and research today, but
no one knows which developments will be important. This
article outlines several areas we find most interesting now.

LTR Inhibitors

One way to look for antiviral AIDS/HIV treatments is to use
laboratory tests to find substances to inhibit the long
terminal repeat (LTR) of HIV. The LTR is a part of the virus
responsible for its activation. If the LTR is inhibited, the
virus does not reproduce or otherwise do harm.

It is relatively easy to find LTR inhibitors in the
laboratory. But unfortunately, this approach has barely been
used for drug development (it is used more often in basic
research). But when it has been tried, it has suggested some
highly practical leads -- drugs or other substances already
in human use, meaning that if they work at all, they are
immediately available, without the need to create new
technologies or test a new chemical entity.

One potential treatment found with a test for LTR inhibitors
is curcumin, a chemical found in turmeric, the mild spice
used in curry. SEARCH Alliance, a community-based research
organization in Los Angeles, is completing a small trial to
see whether curcumin can reduce HIV activity in people. The
results, now being checked and analyzed, will be available
soon. Meanwhile, the anecdotal reports which AIDS TREATMENT
NEWS is receiving about curcumin and about turmeric continue
to be few, but positive.

We plan to publish an in-depth article about LTR inhibitors
in the near future. Also, we will report the curcumin results
when they are available. For background on LTR inhibitors,
see AIDS TREATMENT NEWS #174, May 7, 1993, and #188, December
3, 1993. For background on curcumin, see #174, and also #176,
June 4, 1993.

New Viral Tests

The blood tests now in general use to measure viral activity
(especially the p24 test, and even the improved ICD p24), are
increasingly regarded as unreliable by scientists. The
problem is that these tests can give low numbers, often zero,
when actually the virus is very active.

New tests, which measure the HIV RNA which is produced by the
virus, seem to provide a much more accurate measure of viral
activity. This is important for at least three reasons:

* First, more accurate tests will make it much easier to
determine whether a potential drug is working in people. With
reliable results, fewer volunteers will be needed for each
trial. This means that many treatment leads which otherwise
would be ignored can be tested. It also means that many
"alternative" treatments can at last be tested
scientifically.

The most obvious clinical-trials use for these new methods
is, of course, to test antivirals. But the same viral tests
may also be useful in evaluating immune therapies. A major
problem in developing immune therapies is that we do not know
what to look for in order to measure them, because so much is
unknown, both about the immune system and about HIV disease.
But for many years after infection, the immune system does a
much better job of controlling clinical HIV disease than any
drug known. If an immune treatment can restore some of that
ability, as measured by a significant drop in viral activity,
then the treatment is probably working.

* The second use for better viral tests is for individual
patient management. By indicating which drugs or combinations
are working -- and when they stop working -- the tests can
guide physicians in the better use of existing drugs.

* The third major importance of better viral tests is that
they will help researchers gain a better understanding of HIV
disease itself.

For background on two new tests for HIV RNA -- quantitative
PCR, and the branched DNA assay -- see "Better Viral Tests:
Interview with Mark B. Feinberg, M.D., Ph.D.," AIDS TREATMENT
NEWS #186, November 5, 1993.

New Efforts to Evaluate and Improve AIDS Research

In 1993 a number of projects have been organized to seriously
evaluate what has been done in AIDS research until now, what
has worked and what has not, and to make changes so that
treatment research and development will be more successful.
These efforts sometimes differ and sometimes overlap; it
seems that different teams have responded independently to
the same compelling needs. This is not necessarily bad, since
nobody knows which efforts will work; some redundancy gives
additional assurance that reform will occur.

We believe that potentially the most important of these
efforts is the National Task Force on AIDS Drug Development
(for background, see AIDS TREATMENT NEWS #188, December 3,
1993), because it has the high-level support and involvement
that was so missing during the first years of the epidemic.
In the past, when it was clear that something needed to be
done, there was no one to tell about it, since there was no
one even remotely in a position to deal with the fact that
the research underway could not possibly have met the public
need even if it was technically successful. AIDS TREATMENT
NEWS often published proposals for more productive
approaches, with full knowledge that they had no chance of
being considered in any context in which implementation was
possible -- since there was no such context. Now there is a
chance to move forward, although of course there is no
guarantee.

Other efforts to improve research include the Inter-Company
Collaboration on AIDS Drug Development; Future Directions in
AIDS Research; Project Immune Restoration; and the Barbara
McClintock Project to Cure AIDS.

High-Tech Mainstream Experimental Treatment Approaches

In this area we include technologies such as protease
inhibitors, various gene-therapy approaches, and new immune
treatments like IL-12 and cell expansion. Some news from
these fronts is included in the report in this issue from The
First National Conference on Human Retroviruses and Related
Infections (see below).

While these treatment developments need to be watched, it is
clear to almost everyone that mainstream treatment research
and development have been disappointing. We believe that the
main problem is that the U.S. research effort, by far the
world's largest, got started in some wrong, or limited,
directions early on -- which is normal in early research. But
now much momentum has developed, and it is hard to move to
better ways of doing things. As a result, researchers'
efforts are spent in maintaining ongoing efforts which cannot
produce important advances.