Human Retroviruses and Related Infections -- Major U.S. Scientific AIDS Conference of 1995. Part I


With no International Conference on AIDS this year (in the
future, that meeting will occur only in even-numbered years),
the Second National Conference on Human Retroviruses and
Related Infections, January 29 - February 2 in Washington,
D.C., with about 2300 people attending, was probably the
largest conference on AIDS basic science and clinical trials
to occur in 1995. Many felt that this was a better conference
than most, with a higher quality of work presented and a more
consistent focus on important research issues, reflecting
improvements in the research today. There was more sense of
optimism, based on a growing understanding of HIV, and
growing agreement on some of the important research
directions.

Lack of access by persons with HIV was a serious problem,
however. The conference was expensive -- $425 on-site
registration. The absence of corporate advertising booths may
have been a welcome contribution to the focused scientific
atmosphere, but also meant that the considerable expenses of
the meeting had to be paid largely by those who attended. And
there were no HIV scholarships, which meant that few people
with AIDS could go unless they could register as press.
Because many people were not there, AIDS TREATMENT NEWS is
expanding its coverage of the information presented.

We urge organizers of future AIDS conferences to re-think the
entire project in view of the development of computer
communication. As much as possible of the information to be
presented -- in writing, slides, and eventually video --
should be released on the Internet BEFORE the conference, and
made freely copyable so that it will be immediately available
to AIDS physicians and other service providers throughout the
world. Future conferences will focus less on formal, mass
lectures, and more on working groups of people who need to
meet face to face to discuss and extend the information
already released.

Highlights

These are some of the areas we found most memorable and
important:

* Protease inhibitors. This new class of HIV treatments --
not yet widely available to patients -- is getting the most
research and public attention today. It is fairly clear that
protease inhibitors will be an important advance in AIDS
treatment, but will not be the answer. They will need to be
used in combination -- with each other, and with other drugs.
Their development is one of a number of incremental steps
toward better treatment. The new information presented at the
conference was about as expected -- neither more nor less
optimistic. More information should become available next
week at the protease meeting of the National Task Force on
AIDS Drug Development.

* 3TC plus AZT. This treatment is more widely available, at
least to U.S. patients who are failing other treatments. Data
from U.S. trials presented at the Human Retroviruses meeting
basically confirmed the data from European trials presented
in Glasgow last November (see AIDS TREATMENT NEWS #212,
December 2, 1994). But as at the Glasgow meeting, most of the
data now available is only for the first 24 weeks of the
trial, and is only from blood tests; also, there was a fairly
high dropout rate from both the European and U.S. trials.
And, as expected, the results are less dramatic for people
who have already used AZT extensively. The apparent benefit
of this combination is not enough to keep skeptics from
arguing that it may be no better than other combinations
already available; for example, both 3TC plus AZT and ddC
plus AZT caused comparable reductions in viral load (almost
10 fold) sustained at least for 24 weeks and perhaps beyond
48 weeks, when they were compared head to head in the same
trial. But the general sense is that the AZT plus 3TC
combination appears to give better and especially more
sustained blood-work improvement than more standard
combinations, and probably to be safer as well.

* Long-term non-progressors. It is now generally believed
that not everyone with HIV disease will eventually become
ill. About five percent are "long-term non-progressors" --
defined in one study as persons who have had HIV for at least
seven years, have stable CD4 counts over 600, and no HIV-
related illnesses. (Although the definition specified seven
years, most of the people studied have been HIV-positive and
stable for over ten years.)

While this information is not new, an important report
appeared in the NEW ENGLAND JOURNAL OF MEDICINE on January
26, just before the Human Retroviruses conference -- and the
conference seems to have marked a change in the "conventional
wisdom" about HIV, the general assumptions that pass
unthinkingly into newspaper stories, etc. In the past, the
conventional wisdom had been that everyone would probably
progress to AIDS eventually. Now the conventional wisdom is
that, as far as we know today, about five percent of people
with HIV will never become ill as a result.

Another study presented at the Human Retroviruses conference
used statistical methods to project AIDS-free survival, based
on data from the MACS project, which includes a large cohort
of men with HIV who have been followed for many years. This
study predicted that about 13 percent of people with HIV
would be AIDS-free 20 years after they became HIV positive.

There is no contradiction between the five percent estimated
by one study, and the 13 percent estimated by the other. This
is because there are many kinds of long-term survivors, not
all of whom fit the above definition of "long-term non-
progressor." The 13 percent probably includes the five
percent who may never get sick as a result of HIV infection,
and others who will develop AIDS but very slowly, after 20
years or more -- unless better treatments are found by then.

Neither figure includes another group, who are HIV negative
but whose immune systems show that they have been exposed to
HIV in the past. This group may have recovered from HIV
infection, or may have had a small exposure which did not
result in infection.

It is clearly important to study all kinds of long-term
survivors, to find out what is different about them and/or
about their virus. This information might lead to new ways to
treat HIV disease, whether or not it has already progressed
to AIDS.

* Clinical trial design. There were signs of movement toward
consensus on this controversial issue -- perhaps more in the
hallway conversations and overall atmosphere of the meetings
than in the formal sessions on this topic. And it was
encouraging to see that seemingly obscure meetings on
clinical trials could pack large lecture halls.

The general professional opinion is clearly accepting viral
load as a useful measure, and wants to see it used in small,
rapid trials (the position we have long advocated in AIDS
TREATMENT NEWS), while also acknowledging that there is much
to be learned about how well viral load reduction translates
into clinical benefit to patients. A minority does not argue
that viral load is useless, but rather that it is unproven.
These people are concerned that we could be making a mistake
-- that "treating the marker" (blood test value) may not mean
that we are "treating the patient" -- in other words, that
the strategy of lowering viral load might not prove helpful.
They point to the Concorde trial, which showed that early use
of AZT raised the T-helper count but did not lead to longer
survival, as an example of the need for caution in judging
drugs by blood-test results. They want to see a large trial
to test the strategy of changing drugs to lower viral load,
compared with changing drugs by other criteria without using
viral load, to prove that viral load is superior for this
purpose.

The practical controversy is between those who emphasize
small, rapid, data-intensive trials generally using blood
tests, and those who emphasize large, long-lasting trials
with "clinical endpoints" -- statistics on how many people
progress to more serious illness or death. But a working
compromise seems to be developing. Those who want the large
trials know that there can be very few of them (because of
the limited number of qualified patients, as well as limited
money, trained personnel, and other resources); therefore,
rapid small trials will be needed to find the best treatments
to put into the large trials. And those who emphasize small
trials know that large trials will also be necessary, and
that these large trials will help to define the appropriate
use of viral load and other blood tests for studying new
drugs in the future, and for managing patient care.

* New immune-function tests. Even with viral load tests in
addition to T-cell counts, doctors are missing something
important -- measures of how well the T-cells are working.
Specialized research tests can measure immune function, but
they have been labor intensive, expensive, and inherently
imprecise. They are not suitable for widespread use, and even
research use can be problematic.

Now there is a new kind of immune-function test, based on an
"early activation" marker called CD69; this test is becoming
commercially available for research use (but not for routine
patient care) this month. The new test has many advantages.
It uses whole blood at body temperature, greatly simplifying
the procedure and leaving the cells in their natural
environment, so that the test result will better reflect how
the cells behave in the body. The entire procedure takes a
few hours, compared to two weeks for earlier methods; only a
few minutes of labor is required, and no radioactivity is
used. Also, the cells are typed and measured individually,
while previous methods gave bulk answers; variations of the
technique can even show the production of certain substances,
such as IL-2, within each cell. And the new test is
inexpensive -- probably well under $100 for reagents and
labor. An expensive flow cytometer is required, but many
laboratories have one already; they can begin running these
tests at little start-up cost, only a few thousand dollars
for reagents. The major barrier to widespread use is
conceptual; this new technology makes possible many different
immune tests, and doctors do not know what tests to order or
how to interpret the results.

Different patients can have the same disease status by all
conventional measures, but have different results on immune
function tests, predicting different disease outcomes. As
more becomes known, these tests will be used not only to
study the pathogenesis of HIV disease, but also to see if
treatment or lifestyle changes are correcting the immune
defects they find. Much research will be necessary before
this technology can become part of routine care; but existing
AIDS research organizations, including specialized medical
practices, can begin this research now.

The Human Retroviruses conference had only one poster
involving this technology, which has been developed by
Beckton-Dickinson Immunocytometry Systems and is being
marketed under the name FastImmune (TM) (see poster #174,
"Diminished V-Beta T Cell Subset Responses to Superantigen in
HIV+ Individuals as Determined by Multiparameter Flow
Cytometry," VC Maino, JJ Ruitenberg, MA Suni, L Mole, and M
Holodniy; also see abstract #504A from the Yokohama
conference, "Rapid Flow Cytometry Detection of T Cell Subset
Activation in AIDS," by the same research group). We will
continue to report on these and other immune-function tests
as we learn more about them.

[Part II of this article will continue our report from the
Human Retroviruses conference.]