Yokohama Conference Overview

The Tenth International Conference on AIDS, August 7-12 in
Yokohama, Japan, generated the usual media gloom about the
lack of effective treatments. The gloom is understandable;
AIDS treatment development has been a disaster (despite all
the attention to the one major success of the last year, the
two-thirds reduction of transmission of HIV from pregnant
women to their babies by use of AZT). But the press did not
report the intense interest behind the scenes, the fact that
this conference may have marked the release of more useful
scientific advance than any other.

For example, research into long-term survivors, and other
studies of the pathogenesis of HIV disease, started being
taken seriously about two or three years ago, and the results
are now coming in. It is now widely suspected that there are
some people who are infected with HIV but who may never
progress to AIDS or other illness. And careful laboratory
studies of ten long-term nonprogressors, reported by David D.
Ho, M.D., of the Aaron Diamond AIDS Research Center, found
that the T-helper cells of these people had no special
resistance to HIV infection, and yet the level of virus in
their blood was extremely low. What seemed to be protective
was a very strong immune response, mainly due to their CD8
cells, and also due to neutralizing antibodies. (Other
researchers have found that some CD8 cells produce a soluble
substance, which has not yet been identified, which prevents
the growth of HIV; it is now known that this substance works
as an inhibitor of the LTR, the long terminal repeat, of the
virus.) Also, the virus in those nonprogressors often
appeared to be defective or attenuated. While information
like this does not immediately provide a new treatment, it
provides guideposts for understanding what needs to be done
to control HIV infection, why the current drugs are not doing
so, and what might be needed in drugs which would work
better. This does not, of course, give people something they
can use today.

HIV RNA Tests

What we believe is the most important development that people
can use now -- although it is still experimental, and just
beginning to come into clinical practice -- is measuring
viral load or viral activity by testing for HIV RNA, either
by quantitative PCR or by the branched DNA (bDNA) assay.
These tests, which tell how much virus is circulating in the
blood plasma, were discussed in detail in our last issue
(AIDS TREATMENT NEWS #204, August 5, 1994), which was
published before the conference; and we went to Yokohama
primarily to learn more about this development. We were
surprised by the breadth and depth of research interest, with
RNA testing coming up in session after session, and much new
data reported. The strong consensus of the researchers is
that the level of virus in blood plasma can be tested
accurately and consistently with the RNA tests, and that this
measurement probably does provide useful information about
how well treatments are working, although this is unproven
until more research is done. Some are concerned about RNA
tests coming into routine use in clinical practice at this
time, before more is known about how to use them, but it is
widely recognized that increased clinical use is imminent.

Why do we believe that this is important? One reason is when
a person is about to start a new antiviral drug, or make a
change in their ongoing antiviral treatment (such as a
different dose, or a different combination therapy), it is
now possible to get a good idea, within about a month, of how
well the new treatment is working for them. They need to get
a baseline test before making the change, and then get the
test again a few weeks later, to see if the level of virus in
the blood has gone down, and by how much. (The RNA level can
change very rapidly, even in a few days, so it is necessary
to get the baseline test before starting the new treatment,
in order to test that treatment correctly; it is not good
enough to be tested shortly after starting.)

If the new treatment is not an antiviral, but some other kind
of treatment for HIV disease such as an immune-based therapy,
then the HIV RNA test might still be useful, as a measure of
whether the treatment is helping the body to control the
virus. But much less is known about how to interpret the test
results in this case; we will have to learn, either from
clinical trials or from clinical experience, what can be
expected from various treatments, and how long it may take
for the level of virus in the blood to change.

Also, note that RNA measurements can be used in the same way
to test a "mainstream" treatment (such as AZT or ddI), or an
"alternative" treatment (such as herbal or other substances
that may have anti-HIV activity). As a result, there is now
more reason to be interested in alternative treatments than
there used to be. This is because the biggest problem with
many alternative treatments was that there was no way to ever
find out if they were working -- since there would never be
enough money or other resources to run a clinical trial
powerful enough to see if the treatment helped the "average"
patient. Now it is possible to watch the effect in an
individual person; and if the effect is striking enough, and
is seen often enough, then the resources will be mobilized to
run a formal trial and get a general answer. As a result, the
hundreds of unproven treatments that people do use will now,
for the first time, have a chance to prove themselves; the
best are likely to come to light and move forward into
trials. The resulting contribution to better AIDS treatment
could be incalculable.

Practical Treatments

There were few practical treatments reported in Yokohama
which were not already known before the meeting. But the
results of a trial of human growth hormone as a treatment for
wasting syndrome became available to the researchers only in
recent weeks, and were reported in Yokohama for the first
time. We interviewed the presenter afterwards, and summarized
the results in an article which appears in this issue. There
have been other trials of human growth hormone for wasting
syndrome, but this one is by far the largest and best
designed.

There were many other reports which were suggestive of new
treatment possibilities, or which may have immediate
practical use for physicians and patients. We are still
reading the conference materials and contacting experts for
additional information, which we will present in future
issues.