AIDS TREATMENT NEWS Issue #251, July 19, 1996

   phone 800/TREAT-1-2, or 415/255-0588

CONTENTS:

Vancouver in Perspective

New View of Antiretroviral Treatment: Illustrations from 
"Late Breaker" Abstracts

Expert Panel's New Recommendations for Antiviral Treatment

After Vancouver: Documenting Improved Survival

Other Vancouver News


***** Vancouver in Perspective

by John S. James

The XI International Conference on AIDS took place in 
Vancouver, British Columbia, officially July 7-12 (but almost 
all of the working meetings occurred in only four days, 
Monday July 8 through Thursday July 11). No one could have 
missed the news reports of major treatment advances, the 
messages of hope. It is true that great progress has occurred 
within the last year; the Vancouver conference brought this 
progress to wider attention, and also released additional 
supporting data.

The media also reported some of the limitations and need for 
caution on the new treatment approaches. Much remains to be 
learned about how to use available treatments best. Patient 
compliance with physicians' instructions is both increasingly 
important and increasingly difficult. The high prices of the 
drugs and combinations used will prevent most people in the 
world from having any chance of access, and are likely to 
interfere with medically indicated treatment in all 
countries. The media largely failed to report that much 
(although not all) of the new data are from the patients who 
are easiest to treat -- persons with relatively early stage 
HIV disease and little or no prior treatment. (While the same 
strategy -- reducing the viral load to near zero -- also 
applies to those with advanced illness, on the whole those 
with more advanced HIV disease are more difficult to treat, 
because the virus is harder to control, the patients are more 
likely to have side effects from the drugs and combinations, 
and prior treatment may have produced viruses resistant to 
some of the available drugs. Better drugs and better 
information on how to use them are both required.)

In short, while there has been progress, much more is needed; 
and meanwhile, application of the existing knowledge to 
individual patients will often be difficult.

What Is New?

Several recent changes have contributed to the central good 
news coming from the Vancouver conference. (There is much 
additional news from the conference as well, most of it 
positive; we will look at some of those other developments 
later.)

(1) The arrival of protease inhibitors and other new 
antiretrovirals -- providing more and better elements for 
building combination treatments against HIV.

(2) Impressive data from a number of clinical trials which 
used protease inhibitors in combination with other drugs 
(usually antiretrovirals such as AZT which are already 
approved and in wide use).

(3) Widespread consensus that viral load is important, for 
monitoring individual patients as well as for testing new 
drugs.

(4) Evidence from separate trials of different drugs that the 
development of viral resistance can be greatly slowed 
(possibly suspended entirely) if viral load can be kept low 
enough, preferably near zero.

Point #4 needs more explanation. For several years there has 
been laboratory evidence that HIV develops drug resistance 
much more slowly when multiple drug combinations are used. 
Biological theory supports this observation; resistance to 
multiple drugs usually requires multiple mutations in the 
same virus, and since mutations happen during replication, if 
replication is shut down, new mutation combinations do not 
have a chance to arise. Viral load measured in the blood is 
becoming accepted as a good indicator of the amount of new 
HIV being produced in the body. If viral load can be reduced 
hundreds of times or more by appropriate drug therapy, the 
mutations needed for multi-drug resistance are likely to take 
correspondingly longer to occur.

While the theory and laboratory data have long been 
available, confirmation from human trials has been delayed, 
for at least two major reasons. First, the antivirals in wide 
use until recently were not powerful enough by themselves to 
shut down viral replication sufficiently to allow this delay 
of resistance to be easily seen in clinical trials. Also, 
companies have been unenthusiastic about testing their drugs 
in combination with those of competitors; recently they have 
learned that they must do such trials, because probably none 
of the available individual drugs is powerful enough to have 
a permanent antiviral effect by itself.

What is new recently, and has come to widespread attention 
since the Vancouver conference, is human data from trials of 
antiviral combinations sufficiently powerful to keep HIV 
replication low enough to prevent rapid development of 
resistance:

(1) Drugs which cannot be used alone (because HIV develops 
high-level resistance quickly) can remain effective for a 
long time if used in the right combinations. (No one knows 
how long this will last, as the trials are still ongoing.) In 
one example, the recently-approved drug nevirapine plus AZT 
plus ddI provided viral suppression comparable to protease 
inhibitor combinations but without using any protease 
inhibitor, in patients with CD4 counts from 200 to 600 who 
had not been previously treated. But some patients decided to 
stop taking the ddI (the most difficult of the three drugs to 
use), and then their virus developed high-level resistance to 
the nevirapine. The take-home message is that viral 
resistance can be greatly delayed, but only if the drugs are 
used correctly. This might require suppressing viral 
replication to negligible levels.

(2) Even more importantly, in some of the new trials of 
powerful combination treatments, viral suppression seems to 
get better with time and then remain stable, as measured by 
the proportion of the study volunteers in whom virus is 
undetectable in the blood by any test (there is still virus 
in the lymph nodes, but it is being suppressed by the drugs 
and not apparently reproducing significantly). In previous 
clinical trials, there would be a peak antiviral effect, 
usually within a few weeks, but then HIV would return as it 
developed resistance to the drug or drugs used -- meaning 
that it was only a matter of time until the treatment stopped 
working, or had greatly reduced activity. Now it appears that 
antivirals may remain effective for a long time. No one knows 
how long, since few of the new trials have run for more than 
a year so far (and only a few patients are providing the 
longest data).

HIV-related symptoms have often improved or disappeared in 
these trials.

While most of this research has focused on patients who are 
easiest to treat (because companies want to make their 
products look good), an important Merck study was able to 
suppress HIV to undetectable levels in over 80% of the trial 
volunteers -- despite the fact that they started this trial 
with a median CD4 count of 142, viral load over 40,000, and 
prior AZT treatment of more than two years. (But none of the 
volunteers had prior experience with the other two drugs 
tested in this trial.) And Abbott's previous study of its 
protease inhibitor ritonavir (see AIDS TREATMENT NEWS #240, 
February 9, 1996) found a strong survival benefit from adding 
it to existing antiretroviral therapy, in persons with CD4 
counts from zero to 100.

It is widely suspected that when changing therapies, adding a 
single drug to a failing combination is usually a mistake -- 
that at least two new drugs, without cross resistance to 
treatments previously used, should be started simultaneously.

The early trials of multi-drug combinations (usually 
including at least one protease inhibitor) have suggested 
that for many patients, probably most, it is now possible to 
suppress viral replication to undetectable levels. Assuming 
these people keep taking the drugs as directed, no one knows 
if their disease will ever progress; at this time there is no 
evidence suggesting that it will. Without treatment, almost 
all of these patients would eventually progress to AIDS. And 
if they become careless in taking the drug, resistance is 
likely to develop, making the treatment unable to control the 
virus.

A practical problem in widespread use of this strategy of 
essentially complete suppression of viral activity is that, 
for best results, it should start as early as possible -- 
like treatment for any infectious disease. This means that 
many patients will still be relatively healthy -- and likely 
to remain so for some time. Will they be willing to start a 
regimen of 10 to 15 or more expensive pills a day, taken on 
an exacting schedule, some requiring an empty stomach and 
some requiring meals -- and continue this regimen for years, 
perhaps for life? There are likely to be side effects of the 
medications, especially in the first few weeks. And missed 
doses, "drug holidays," or other failures to use the drugs as 
directed could result in the therapy doing more harm than 
good due to the development of resistant viruses -- which not 
only would harm the individual, but also could be transmitted 
to others, depriving them of the benefits of the new 
treatments. Sometimes it might be best to defer treatment 
until one is ready to make the commitment to use the drugs 
properly. These are some of the issues that physicians, 
patients, and others must work with, in applying the 
developing scientific knowledge in widespread medical 
practice.


***** New View of Antiretroviral Treatment: Illustrations 
from "Late Breaker" Abstracts

by John S. James

The previous article outlined the new view of antiretroviral 
therapy which has emerged in the last several months, and 
which has been responsible for much of the optimism emerging 
from the XI International Conference on AIDS in Vancouver. 
Here we examine some of the research leading to the new view 
of antiretroviral treatments. For this purpose, we selected a 
few of the "late breaker" published abstracts to review. (The 
"late breakers," at this and some other conferences, are 
reports of new research too recent to be submitted by the 
regular deadline -- which is usually months in advance of the 
meeting -- but were judged important enough to include anyway 
in a special session.)

[We are preparing a full report on how to obtain abstracts 
and other documentation from the conference. One way to 
obtain selected abstracts is through the World Wide Web, 
http://sis.nlm.nih.gov/aidsabs.htm . If you have the printed 
Vancouver conference abstracts, note that the late breakers 
are not included in the regular two-volume set, but are 
available in a short PROGRAM SUPPLEMENT, which was quickly 
published on newsprint and distributed at the conference. If 
you have the conference abstracts on disk or CD-ROM, the late 
breakers are included.]

Note: (1) In this article we did not include studies 
combining two protease inhibitors, because these need more 
extensive coverage. (2) Most of the abstracts sited have 
multiple authors; we listed the presenting author here.

* Bi-Directional Inhibition of HIV-1 Drug Resistance 
Selection by Combination Therapy with Indinavir and Reverse 
Transcriptase Inhibitors. By JH Condra and others, #Th.B.932.

This report from Merck Research Laboratories looked at the 
emergence of drug-resistance mutations in two different 
clinical trials, both of which compared indinavir (Crixivan(R), 
the Merck protease inhibitor) alone, vs. nucleoside analog 
therapy alone, vs. the combination. In one case, the 
nucleoside analog therapy used was AZT; in the other trial, 
it was AZT+ddI.

In both trials, the use of the protease inhibitor greatly 
reduced the development of resistance mutations to the other 
drug or drugs. In the trial testing indinavir vs. AZT vs. the 
combination, only one of 22 patients on the combination 
developed AZT resistance mutations, vs. 11 of 17 patients who 
received the same dose of AZT alone. In the trial of 
indinavir vs. AZT+ddI vs. the three-drug combination, zero of 
20 patients in the three-drug combination developed either 
AZT or ddI resistance mutations, vs. 10 of 16 of the patients 
who received only AZT+ddI. Both these results were highly 
statistically significant, showing that using indinavir in 
the treatment regimen greatly reduced the development of 
viral resistance to the other antiretrovirals.

Going the other way, the nucleoside analogs also reduced the 
development of resistance mutations to indinavir -- but here 
the effect was less. Using AZT with indinavir reduced the 
indinavir resistance mutations from 9 of 21 patients to 4 of 
22 -- a trend, but not statistically significant. Using 
AZT+ddI with indinavir reduced the occurrence of indinavir 
resistance mutations from 13 of 24 patients to 2 of 20, which 
was highly statistically significant.

Comment: The two classes of drugs (protease inhibitors and 
nucleoside analogs) work at different stages of the viral 
life cycle; there is no reason to suspect that one drug could 
directly affect resistance mutations to the other. Instead, 
what seems to be happening is that adding a drug to the 
regimen results in a lower level of HIV replication overall, 
so there is less chance for mutations to develop. This effect 
was strongest with indinavir, because it is the most active 
antiretroviral used in these trials; it was weakest with AZT 
alone, which was the least active antiviral tested.

This result gives measurable data on why combination therapy 
is important -- and emphasizes the need to follow medical 
instructions carefully when using antiretrovirals, so that 
the drugs are in fact reaching the virus at effective 
concentrations in the combinations prescribed.

* Potent and Sustained Antiretroviral Activity of Indinavir 
(IDV), Zidovudine (ZVD) and Lamivudine (3TC). By RM Glick and 
others, #Th.B.931.

This study is important because it shows a strong sustained 
effect (at 48 weeks so far) of one of the most popular new 
three-drug combination treatments.

The patients in this trial had CD4 counts of 50-400, viral 
load over 20,000 copies, and at least six months of prior AZT 
treatment, but no treatment with 3TC or any protease 
inhibitor. They were randomly assigned to either indinavir 
(Crixivan(R), the Merck protease inhibitor) alone, AZT+3TC 
alone, or the triple combination of all three drugs. Viral 
load was measured at 24, 32, and 44 weeks; the viral load 
test used had a lower limit of detection of 500 copies per 
ml. There was relatively little drop-out, with 90 of 97 
patients continuing on the study after up to 52 weeks of 
followup.

With the triple combination, at week 24, 92% (22 of 24) 
patients had viral load below 500 copies (undetectable on the 
test used). At 32 weeks that was 83% (19 of 23 patients). At 
48 weeks it was 83% (5 of 6 patients; the numbers are small 
because the trial is still continuing and most of the 
patients have not reached the 48 week point).

For those on indinavir alone, the percentages with 
undetectable virus are 38% at 24 weeks, 36% at 32 weeks, and 
22% at 44 weeks. For those on AZT+3TC alone, with no protease 
inhibitor, the percentage with undetectable virus was zero at 
all time points.

Note: A Merck press release dated July 11 gave slightly 
updated figures, but the overall picture did not change. The 
press release also gave median CD4 cell increases at 44 
weeks: 218 for the triple combination (for 7 patients 
completing the 44 weeks so far), 158 for indinavir alone, and 
14 for AZT plus 3TC (in these patients with much previous 
treatment with AZT).

Comment: In this and similar trials, the measurement of most 
interest is usually the proportion of patients whose viral 
load goes below the level of detection of the test (as close 
to zero as possible to measure in the trial). The log viral 
load drops were also reported, but these are likely to 
understate the effect of a drug which causes many patients' 
viral load to drop below the test limit. For example, in this 
case, since the lower limit of detection of the test was 500 
copies, anyone with under 50,000 copies at baseline could not 
possibly record more than a two-log (100-fold) drop, since 
the test used could not record the resulting level.

This is one of several clinical trials now showing that 
certain protease inhibitor combinations can largely shut off 
viral replication for a long time at least in a large 
majority of patients. It is impressive that the volunteers 
entering this trial were relatively advanced (median CD4 
count 142, median viral load 41,130 copies) and with 
considerable prior experience with AZT (median 31 months), 
and the combination still worked. In further research it will 
be important to check viral load with the newer "third 
generation" tests (not yet commercially available), which go 
down to about 25 copies; it is likely that if a combination 
is starting to fail, that may first be signaled by a small 
rise in viral load, which undetectable with the 400-copy 
cutoff of the currently approved viral load test, and which 
could serve as an early warning to change the drug regimen 
quickly to keep the virus under control. But it is not yet 
known whether or not the more sensitive test would make much 
practical difference.

* Triple Therapy with AZT and 3TC in Combination with 
Nelfinavir Mesylate in 12 Antiretroviral-Naive Subjects 
Chronically Infected with HIV-1. By M Markowitz and others, 
#LB.B.6031.

This trial enrolled 12 patients to test triple combination 
therapy with the Agouron protease inhibitor nelfinavir. One 
withdrew due to apparent drug toxicity (grade 4 CPK 
elevation); all of the other 11 had viral load below the 
limit of detection (500 copies with the test used) at 12 
weeks. These patients entered the trial with a median CD4 
count of 253 and a median viral load of 4.91 log (about 
81,000 copies). The median starting CD4 count was 253, and 
the median increase was 98 at 12 weeks.

* Triple Therapy with AZT, 3TC, and Ritonavir in 12 Subjects 
Newly Infected with HIV. By M Markowitz and others, 
#Th.B.933.

This study recruited 12 patients with very early HIV 
infection; antiretroviral treatment was started an average of 
65 days after the symptoms of primary infection began. 
(Primary infection is the initial stage of very rapid viral 
growth shortly after HIV infection occurs, when the body has 
not yet developed an immune response to the virus; often 
there are severe flu-like symptoms.) Baseline viral load 
varied greatly, but became undetectable after treatment in 
all but one of the volunteers (one was slightly over the 
cutoff). Virus could not be cultured from any patient.

Incidentally, 9 of the 12 believed they knew when they were 
infected; this varied from 6 to 20 days before the start of 
symptoms.

Comment: Many researchers believe that primary infection may 
be the best time to begin aggressive antiretroviral 
treatment. Unfortunately primary infection is difficult to 
diagnose; many patients have no symptoms at all, probably few 
suspect HIV, and most will see a general-practice physician 
if they see a doctor at all, and be sent home with a 
diagnosis of "viral syndrome." If it is confirmed that 
primary infection is the best time to begin therapy, locating 
these patients will be a challenge for the medical system.

Another late breaker reported a single case of apparently 
beneficial treatment of primary infection, with AZT plus 3TC 
plus saquinavir. (Rapid Viral Load Decrease in Primary 
Infection Associated with Aggressive Therapy. By C Workman 
and others, #LB.B.6021.)

* How Long Should Treatment Be Given If We Had an 
Antiretroviral Regimen that Completely Blocks HIV 
Replication? By DD Ho and others, #Th.B.930.

This research, at Los Alamos National Laboratory and the 
Aaron Diamond AIDS Research Center, looks at the possibility 
that HIV might be eradicated just by completely suppressing 
its replication for long enough. (Whether this will really 
happen or not is unknown at this time.)

In this study, mathematical models were developed based on 
data from eight patients treated with the experimental 
Agouron protease inhibitor nelfinavir plus AZT plus 3TC. 
There is a two-phase decay of viral load when HIV replication 
is stopped by drugs. In the first phase, viral load drops 
about 100 fold in two weeks; this is due to the clearance of 
free virus and the loss of productively infected cells. The 
second, slower phase of viral load decay appears to be due 
either to longer-lived infected cells such as macrophages, or 
to the gradual activation of latently infected cells; the 
researchers do not know which. In either case, the 
mathematical model suggests that completely inhibitory 
treatment would need to be used for about 1.5 to 3 years 
before the second phase burns out.

The researchers note that there could also be a slower third 
phase, or a "sanctuary" site in the body, which would 
invalidate this projection.

Comment: If HIV can be eradicated from the body just by 
blocking replication completely for a long enough time, then 
it may be possible to cure many patients with drugs which are 
already available. But no one yet knows whether this theory 
will work in practice. No patient has yet had HIV replication 
completely blocked for 1.5 to 3 years, since the trials of 
combination treatments powerful enough to stop replication 
have not run that long. In the few who have had to go off 
treatment early, high levels of virus have returned.

* Improved Survival and Decreased Progression of HIV in 
Patients Treated with Saquinavir (Invirase(TM), SQV) Plus HIVID 
(Zalcitabine, ddC). J Lalezari and others, #LB.B.6033.

In this large saquinavir study, named NV 14256, there were 
approximately equal numbers of patients assigned to the three 
treatment arms (314 for ddC, 318 for saquinavir, and 308 for 
the combination). But disease progression occurred in 85 on 
ddC, 77 on saquinavir, vs. 46 with the combination. There 
were 28 deaths among those assigned to ddC, 34 assigned to 
saquinavir, but only 9 with the combination. Both differences 
are statistically significant.

These patients entered the trial with CD4 count between 50 
and 300, and at least 16 weeks of prior AZT therapy. Median 
viral load at entry was over 100,000 copies.

Comment: Most of the interest today is in at least three-drug 
combinations, but we included this analysis of a large two-
drug trial (saquinavir, the Hoffmann-La Roche protease 
inhibitor, vs. ddC, vs. the two combined) because it shows 
that even a less desirable protease-inhibitor combination 
treatment can make a substantial difference in disease 
progression and death. The relatively poor result with 
saquinavir alone is probably because the current dose of that 
drug is widely recognized as being too low. A new formulation 
which should correct the dosage problem is now in clinical 
trials.

 At this time, the newest studies of the protease-inhibitor 
combinations which are believed to be the most desirable are 
relatively small, and started fairly recently, so there are 
no results yet on reduction of progression to AIDS and death. 
It is widely suspected (but not yet known) that HIV disease 
will not progress at all if viral replication is stopped. And 
it is clear that much immune recovery can occur.


***** Expert Panel's New Recommendations for Antiviral 
Treatment

by John S. James

Major new guidelines for antiviral treatment of HIV infection 
were published July 10 in JAMA ("Antiretroviral Therapy for 
HIV Infection in 1996: Recommendations of an International 
Panel," JAMA, volume 276, number 2, pages 146-154); they were 
announced July 6 in Vancouver at a press conference by the 
American Medical Association, and presented in detail to 
hundreds of physicians and other health professionals at a 
satellite meeting of the International Conference on July 10.

The new treatment guidelines were prepared by a 13-member 
panel appointed by the International AIDS Society-U.S.A. All 
of the panelists (most of whom were on stage at the July 10 
Vancouver presentation) are leading HIV/AIDS clinical 
researchers, and also are physicians who care for patients. 
While the new guidelines are much improved and far more 
aggressive than previous ones, they are already being 
criticized by some researchers as not aggressive enough, 
since they allow but do not necessarily require an attempt to 
completely suppress HIV replication (as indicated by viral 
load being reduced to undetectable levels). These guidelines 
were largely put together by January of this year, with some 
later revisions to reflect new data. They will be changed 
periodically as knowledge of HIV disease changes; however, 
the first revision seems unlikely before late 1996 or early 
1997.

The guidelines focus on "when to start therapy, what to start 
with, when to change, and what to change to." They also look 
at primary infection (the 4 to 7 week period immediately 
following exposure, in which viral load goes extremely high 
and often causes flu-like symptoms), treatment to prevent 
infection in case of needlestick, and treatment to prevent 
mother-infant transmission of HIV.

The 9-page guidelines document cannot be meaningfully 
summarized; persons interested should see the original 
article (referenced above). But some of the key 
recommendations will give our readers a sense of the guiding 
philosophy.

The guidelines recommend therapy for all patients with 
symptomatic HIV disease (which "includes symptoms such as 
recurrent mucosal candidiasis, oral hairy leukoplakia, and 
chronic and unexplained fever, night sweats, and weight 
loss"). For asymptomatic patients, therapy is recommended for 
all with a CD4 count below 500. And for those who are 
asymptomatic with CD4 count greater than 500, therapy is 
recommended for those with a viral load greater than 30,000 
to 50,000 copies or with rapidly declining CD4 cell counts, 
and "should be considered" for those with greater than 5,000 
to 10,000 copies.

What to start with? The guidelines include extensive 
discussion, mostly based on published data from clinical 
trials. A table recommends a number of possible nucleoside 
analog combinations for initial use, with or without a 
protease inhibitor in addition. For an initial antiretroviral 
regimen, possibilities mentioned are AZT+ddI, AZT+ddC, 
AZT+3TC, or ddI alone (the latter may be less effective with 
more advanced disease). Also mentioned (although less data 
are available) are ddI+d4T, d4T+3TC, and d4T alone. Also 
discussed at Vancouver was the class of non-nucleoside 
reverse transcriptase inhibitors (of which only one, 
nevirapine, has now been approved; other possibilities are 
delavirdine and loviride). These did not get into the current 
recommendations, due to lack of information at the time these 
recommendations were put together.

The guidelines listed three reasons for changing therapy: (1) 
treatment failure -- "indicated by increases in viral load 
(e.g., a return toward or within 0.3 to 0.5 log of 
pretreatment plasma HIV RNA levels)" -- (2) toxicity, 
intolerance, or nonadherence, and (3) "Current use of a 
suboptimal treatment regimen. Zidovudine (AZT) monotherapy is 
a suboptimal regimen and treatment should be reevaluated in 
any patient who is receiving it."

What to change to? The guidelines include a table suggesting 
options to change to in case of treatment failure after 
initial treatment with any of five different regimens now in 
common use -- or in case of drug intolerance to three of 
those regimens.

Throughout the Vancouver conference there was much concern 
about the difficulty of following the new antiretroviral 
regimens -- and the dangers of developing viral resistance if 
the medications are not used as directed. Although not stated 
in the new guidelines, there is a widespread belief that it 
may be better to wait until one is committed to using the 
treatments correctly, rather than beginning treatment but 
then pursuing it haphazardly.

Also, there is increasing discussion about the need for 
considering long-term plans when making antiretroviral 
treatment decisions -- including what treatment options 
remain available if the virus develops resistance to the 
first drugs chosen.


***** After Vancouver: Documenting Improved Survival

by John S. James

Leading HIV physicians knew about the major results presented 
in Vancouver well before the conference, and had been using 
some of the new treatments. Already there are anecdotal 
reports of fewer deaths in physicians' practices, compared to 
a year ago or more. We and others involved in AIDS know many 
people who would have been expected to have died long ago, 
based on all experience from the previous decade of the 
epidemic, who instead are alive and doing well.

How can this improved survival best be documented, to show 
that better treatments do make a difference, and to support 
advocacy to make them more widely available? Official death 
statistics usually take a long time to become complete, as 
records move slowly through the system. And the totals by 
city, state, and other regions -- as well as the large cohort 
studies -- reflect an aggregate of those who get excellent 
treatment, poor treatment, and no treatment; these are 
figures we certainly want to know, but because they mix 
different populations, they are likely to underestimate the 
effects of improved treatment.

Another approach could be a telephone survey of major HIV 
medical practices which have been using protease inhibitor 
combinations and other new treatments. Physicians might be 
asked how many deaths, opportunistic illnesses, or other 
events they had in the last year compared with previous 
years, as a proportion of their total patients. They would 
also be asked other questions which could indicate other 
changes in their practice which might explain differences in 
event rates (such as accepting healthier patients, or 
referring those with more advanced illness to other 
specialists). The physicians should be promised 
confidentiality, with only aggregate results being released, 
to avoid creating an incentive for those with good statistics 
to selectively participate in the study.

A small preliminary survey could be done quickly -- and there 
is an important political reason to do it now. During the 
last several months it has been difficult to get increased 
funding for ADAP (the AIDS Drug Assistance Program) and other 
Federal programs to pay for the new treatments -- even though 
the cost of treating AIDS is still a fraction of the cost of 
many other diseases, even when combination therapy and 
protease inhibitors are included -- and even though the new 
treatments are likely to reduce hospitalization, infusion, 
and other major costs. The best time to get the attention and 
commitment of politicians is before the November elections. 
Unfortunately, while a few organizations have been working 
around the clock on these funding issues, most of the AIDS 
community has not yet mobilized. Documentation of reduced 
deaths could help motivate community support, and justify 
funding to make the new treatments available to more people.

A recently published epidemiological study at Johns Hopkins 
University has documented striking survival improvements 
between the period of 1985-88, vs. 1989-93; it attributed the 
lower mortality to widespread use of antiretroviral treatment 
and opportunistic infection prophylaxis (C. Enger, N. Graham, 
Y. Peng and others, JAMA, May 1, 1996, pages 1329-1334). The 
new treatment advances might save even more lives than the 
previous ones, in the practices and localities where they are 
being used.


***** Other Vancouver News

This issue of AIDS TREATMENT NEWS has focused on explaining 
the central message of optimism about antiviral treatments 
which has come from the Vancouver conference. There are many 
other developments to report as well. We plan to focus on 
this conference for the next several issues, including 
reports on:

* Additional antiretroviral and other treatments for HIV 
disease and related conditions;

* "Alternative" and/or low-cost potential treatments (which 
usually means those not sponsored by a corporation);

* Research most needed now, especially small, inexpensive 
projects which could be accomplished by community-based 
organizations with modest independent support;

* Access to care, the international Community Forum held just 
before the main Vancouver conference, and the development of 
international advocacy;

* An overview of some of the most successful AIDS prevention 
strategies;

* How to get documents, summaries, and other reports from 
this conference.


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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 
quotations are used.

