From: "John S. James" <[email-masked]>
Date: 14 May 94 12:40 PDT

AIDS TREATMENT NEWS #198, May 6, 1994
   phone 800/TREAT-1-2, or 415/255-0588

CONTENTS:

Curcumin Trial Results: Antiviral Effect Reported

Resource Articles: ** Protease Inhibitors; ** Interview with 
Roy Vagelos of Merck & Co

d4T Approval: FDA Advisory Committee Meeting, May 20

Acyclovir Over the Counter? FDA Hearing, May 19

AIDS TREATMENT NEWS Volume III Now Available (May 1991 
Through December 1993)

***** Curcumin Trial Results: Antiviral Effect Reported

by John S. James

The first human trial of curcumin -- an "alternative" 
treatment in use in the AIDS community, and the first of a 
potentially new class of anti-HIV treatments which target the 
LTR (long terminal repeat) of the AIDS virus -- found a 
modest antiviral effect, according to SEARCH Alliance, a 
community-based research organization in Los Angeles. This 
was only a pilot study, however; and the effect appeared to 
be temporary, as it had partially faded by 20 weeks when this 
study ended. More research is needed -- such as the new 
curcumin trial, about to begin in Boston, which will be 
conducted by the Community Research Initiative of New 
England.

The antiviral effect was seen in measurements of HIV RNA, 
using an experimental test (quantitative PCR) which is very 
sensitive, but also highly sensitive to laboratory errors and 
variations. P24 antigen tests, which are much less sensitive, 
failed to confirm an antiviral effect; also, there was no 
improvement in average T-helper count. The only toxicity seen 
at the dose tested (which is the most popular dose in use in 
the community), was upper gastrointestinal discomfort in some 
of the volunteers; it was severe enough to cause two of the 
19 to drop out of the trial.

Curcumin is found in the spice turmeric; it is the substance 
which gives curry its yellow color. It first came to the 
attention of the AIDS community after laboratory studies at 
the Dana-Farber Cancer Institute, and follow-up viral tests 
at Beth Israel Hospital in Boston, showed anti-HIV activity 
in the laboratory. Despite publication of these laboratory 
findings more than a year ago in the Proceedings of the 
National Academy of Sciences, USA (March 1993; volume 90, 
pages 1839-1842), no company or government agency is studying 
curcumin as a possible treatment, nor funding anyone else to 
do so. SEARCH Alliance, which specializes in fast-track 
development of the earliest pilot studies of potential AIDS 
treatments, found private funding for its small trial, and 
reported the results on May 3.

Curcumin is the weakest known agent in its class (of 
substances found to inhibit the HIV LTR); it was chosen for 
the trial because more powerful LTR inhibitors were not 
available for this research. All information suggests that 
this treatment technology could be developed much further. We 
hope the SEARCH Alliance results will bring more attention to 
a very important research area which has been neglected by 
the mainstream. But it is also important to remember that the 
results so far are limited and sometimes ambiguous; they do 
not yet prove that curcumin is beneficial.

[Note: This writer is a member of the medical/scientific 
advisory board of SEARCH Alliance; however, this article 
represents only our views, not necessarily those of the 
organization. We originally suggested a curcumin trial to 
SEARCH Alliance; however, we were not involved in designing 
or conducting the study, and we first saw the data on May 2, 
a week before this issue went to press.

[This article is based on "Curcumin As an Antiretroviral in 
HIV-1 Positive Patients," an unpublished manuscript by Robert 
E. Winters, M.D., Michael J. Slattery, Charles V. Chesson II, 
Ph.D., and Natalie L. Sanders, M.D. -- and on additional 
information provided by SEARCH Alliance. Our analysis differs 
from that of the SEARCH team -- we used median values, 
instead of mean values, to summarize the data, as explained 
below -- but while the numbers are different, our conclusions 
are the same.]

Notes on Interpretation of the Data

This was a small pilot study with a total of 19 patients 
enrolled, and 11 completing the trial. There was no placebo 
or other control group. As a result, this trial will not 
provide hard conclusions; it cannot prove that one treatment 
is better than another. What it can do is to give us early, 
suggestive information about a new kind of potential 
treatment in human use -- a more complete and accurate view 
than can be obtained from collecting anecdotal reports.

Therefore, this article will not focus on conclusions, but 
rather walk through the key data, pointing out what we find 
interesting and important.

In both the scientific and activist AIDS communities at this 
time, there is a widespread conservative view that trial 
results must only be analyzed according to procedures 
specified in advance. The purpose of this limitation is to 
prevent errors which can occur when researchers look at the 
data and then concoct theories to fit it; if dozens of 
different theories are considered, some are likely to fit 
just by chance alone, when no real discovery has been made.

We believe that this conservative view is correct for certain 
large trials which are seeking definitive proof of the value 
of a treatment. But it should not apply to initial pilot 
studies, which aim to help researchers find out what is going 
on, not to test or prove a preconceived idea. All too often, 
researchers blindfold themselves, creating theories and 
designing trials abstractly, without looking at enough real 
data; usually these theories are wrong, and then the 
resulting trials are not useful, except as miscellaneous 
negative results. The consequence is inefficient, 
unproductive research. A better way is to run a pilot study 
first, and look at all of its data in various ways, asking 
what the data is trying to tell us; then use that information 
to design a more formal, definitive trial.

In the curcumin study, a related issue concerns analyzing 
subsets of the data. This study sought volunteers with 
advanced HIV disease; the median T-helper count at entry was 
100. Several participants dropped out of the trial, usually 
because of opportunistic infections; and any infection or 
other immune activation is likely to cause a substantial rise 
in HIV RNA, the principal viral measure used in this study, 
making the treatment look less active than it otherwise 
would. As a result, when all the patients who entered the 
trial are analyzed together, the antiviral effect observed is 
small; but when those who completed the trial without an OI 
are analyzed -- or those who entered it with a higher than 
average T-helper count -- the effect is much more clear. We 
present the data both ways.

Also, in this article we have summarized the data using 
median values, instead of mean (average) values. The median 
of a set of numbers is the 50-percent point -- the value such 
that half of the numbers are above it and half are below it. 
We decided to use the median instead of the average, because 
the most important data (the measurement of HIV RNA) are 
highly variable, with a number of extremely high and low 
values which may be due to laboratory errors. The median is 
often used for looking at ill-behaved data, since a few 
extreme values can only cause a limited error in the median, 
no matter how high or low those values may be -- while a few 
extreme values can completely distort an average.

Study Design Overview

The purpose of the SEARCH Alliance curcumin trial was to look 
for any signs of toxicity of the treatment, at the dose 
commonly used in the AIDS community -- and also to record any 
indications of antiviral activity. For this pilot study, all 
patients were enrolled in a single treatment arm; there was 
no control group.

To check for toxicity, the study included "a complete blood 
count with differential, chemistry panel, amylase, and a 
self-evaluation questionnaire at baseline and at the end of 
week 1, 2, 4, 6, 8, 12, 16, and 20." (Quotations are from the 
SEARCH Alliance manuscript, "Curcumin As an Antiretroviral in 
HIV-1 Positive Patients," unless otherwise stated.)

To look for anti-HIV activity, "Viral load was monitored by 
serum RNA-PCR at baseline and at week 2, 4, 8, 12, 16, and 
20." (The manuscript includes a technical overview of the PCR 
test used, and of procedures for quality control.) Also, 
three different kinds of p24 antigen tests were used, in an 
effort to find one which gave enough positive values at 
baseline to allow useful comparisons.

The study was initially designed to last eight weeks. 
However, the data at week four was encouraging enough that 
the trial was extended to 20 weeks.

All study volunteers received the same dose of curcumin. 
"Patients were instructed to take three capsules of 
concentrated curcumin, three times a day, one hour before or 
two hours after meals. Each capsule, supplied by Nature's 
Herbs, weighed 445 mg. and contained approximately 285 mg. of 
curcumin concentrate in a ground turmeric base. The total 
amount of curcumin ingested per day was 2.56 grams." (The 
volunteers were judged "very compliant as determined by 
counting the number of returned capsules," meaning that they 
actually took the intended study dose.) In case stomach upset 
became a problem, the curcumin could be taken with meals.

A total of 19 volunteers entered the study. One dropped out 
after two days, however, and therefore was not included in 
the analysis of antiretroviral data below, since only a 
baseline test was done, so there is no data on changes in 
viral tests.

Inclusion/Exclusion Criteria

Study volunteers could have any T-helper count; however, an 
effort was made to enroll persons with a low count, so that 
they would be more likely to have p24 antigen values which 
could be measured. For the 18 patients, the T-helper count at 
baseline ranged from 10 to 391, with a median of 100.5.

Of the total of 19 who enrolled, 11 finished all 20 weeks of 
the study without an opportunistic infection. (A 12th has 20 
weeks of data, but was not included with the other 11 due to 
an OI.)

Volunteers could use AZT or other antiretrovirals during the 
trial, provided they were on a stable treatment regimen for 
60 days preceding enrollment (so that changes in antiviral 
treatments, such as starting or stopping AZT or ddI, would 
not interfere with the viral measurements in the trial.) All 
of the 11 patients who finished the trial were using 
antiretrovirals; we do not have information on the others. 
Only one started an antiretroviral treatment during the trial 
-- patient number 02, who started d4T. Use of vitamins, 
minerals, and herbs during the study was strongly 
discouraged.

Inclusion criteria also included hemoglobin, white blood 
count, granulocytes, platelets, bilirubin, ALT, AST, SGPT, 
alkaline phosphatase, and creatinine.

The 19 participants included 15 men and 4 women. There were 
two Mexican-Americans, two African-Americans, and 15 
Caucasians. Their ages ranged from 29 to 59 years old.

Results

[Note: The data discussed in this article is reproduced in 
Table I, below. The charts (Figure I through Figure III) 
could not be reproduced here. But the data used to create the 
charts -- the median values, and the counts on which those 
medians are based -- are shown, below Table I. Even without 
the charts, you can use this data to follow the discussion.

[For a copy of the original article including Figure I 
through Figure III, send a self-addressed stamped envelope 
to: AIDS Treatment News, P.O. Box 411256, San Francisco, CA 
94141, or call 415/255-0588.]

One of the 19 volunteers who entered the study, who had a 
history of peptic ulcer disease, withdrew after two days due 
to gastrointestinal irritability. This person is not included 
in the 18 patients analyzed below, since only the baseline 
tests were given, so there are no data on changes in HIV RNA.

One other patient also withdrew due to gastrointestinal 
irritability, after eight weeks. Four others withdrew due to 
opportunistic infections, and two others left for non-medical 
reasons. No patient was lost to analysis. Aside from the 
gastrointestinal irritability, no indications of toxicity 
were found.

The study measured HIV RNA by polymerase chain reaction 
(PCR). It also measured p24 antigen, an older test of viral 
activity. In addition, T-helper count and percent, CD8 count 
and percent, complete blood count with differential, and some 
blood-chemistry values, were recorded throughout the trial.

The primary indicator of viral load -- HIV RNA in the blood, 
as measured by quantitative PCR -- is presented in the tables 
and charts below.

Table 1 shows the raw data on HIV RNA for all of the patients 
in this study (except for the one who dropped out after two 
days). Also, the baseline T-helper count for each patient is 
shown. Even a casual look at this table suggests that those 
with high T-helper counts appear to be responding better than 
others to the treatment. Note that the charts below (Figure 1 
through Figure 3) can all be reproduced from Table I, with no 
additional information required.

Figure 1 shows the HIV RNA data graphically. Also, for each 
time point, the median RNA value at that time, and the number 
of patients in that median, are shown below the chart. Notice 
that there is a substantial spread of HIV RNA values at 
baseline (week 0) and at week 2. But later (with the possible 
exception of week 8, which is discussed separately), the 
pattern is that the most of the values are clustered at the 
low end of the scale -- often clustered so tightly that the 
separate lines cannot be distinguished on the graph. Besides 
these low values, there are a few "outliers," very high 
values which are entirely different from the rest. We do not 
know what these high values represent; some could be 
laboratory errors. [Note: In these graphs (Figure 1 through 
Figure 3), a point by itself only means that the data points 
adjacent to it are missing, so there is no line connecting 
them.]

At week 8, the median is high, about where it was at 
baseline. But, as one can verify from the data in Table 1, a 
change of a single value would have made the median more than 
six times lower. The data at week 8 shows a very unusual 
distribution, with six values under 1,000, two values which 
are both 3900, and the other nine values beginning at 25,000.

If laboratory error accounts for a single one of these high 
values at week 8, the medians would show a clear antiviral 
effect; even as it is, the medians still suggest an antiviral 
effect. And this is with all data included, even from those 
patients who had opportunistic infections, which are likely 
to greatly raise the level of HIV RNA.

Note that no one dropped out of the study until the week 8 
data (there is one missing value at week 4, but this person 
did not drop out at that time). Only one participant had 
dropped out by week 8; and three more dropped out by week 12. 
A low dropout rate is important, because those who are doing 
poorly in a trial are the most likely to leave; this creates 
a selection bias, which can make a drug look good even if it 
really does nothing. With this study, a close look at the 
data shows that the dropouts could not have affected the 
medians very much, even through week 20, no matter how high 
their HIV RNA values might have been.

Figure 2 shows the HIV RNA for patients who completed the 
trial without an opportunistic infection. Here the antiviral 
effect looks very clear, with the median viral load showing a 
drop of 20-fold or more between weeks four and 12. At weeks 
16 and 20 the medians have climbed, but they are still 
several times lower than when the trial began. This suggests 
that the antiviral effect may be temporary, with viral load 
rising again by sixteen weeks.

Figure 2 must be viewed with caution, however, because of the 
likelihood of selection bias. Those who stayed with the study 
to the end (and therefore were counted in Figure 2) would be 
likely to be those who were doing well. Therefore, the 
results shown in Figure 2 are likely to be too optimistic.

Figure 3 shows that patients with less advanced HIV infection 
seem to respond better to the treatment (by having a larger 
drop in viral load) than the group as a whole. It shows the 
changes in HIV RNA for those patients whose T-helper count at 
entry to the study was in the upper half of the group. This 
turns out to be those with a T-helper count over 100. The 
medians do show a good antiviral response in this group. Each 
median is based on a small number of data points; but there 
is a clear pattern, with the medians being much higher at 
baseline and at week 2 than later.

Figure 3 is important because it has less opportunity for 
selection bias than Figure 2. We deliberately selected the 
most healthy patients (at enrollment) for Figure 3; this is a 
legitimate choice, as the trial could have made the same 
selection through its inclusion criteria, and Figure 3 shows 
what would have happened if it did. But (except for a few 
dropouts near the end of the trial), Figure 3 avoids the 
major potential bias of Figure 2 -- the retrospective 
elimination of some patients who turned out to do poorly (a 
choice which could not possibly have been made at the time 
the trial began). The fact that Figure 3 shows a substantial 
drop in HIV RNA after week 4 provides reassurance that the 
antiviral effect is real.

Figure 3 is also reassuring in that it is hard to imagine any 
laboratory bias that could cause those with higher T-helper 
counts at study entry to show more improvement than those 
with lower counts.

Figure 3 also suggests that future curcumin trials might find 
better results in persons with higher T-helper counts.

Discussion and Commentary

The results of this trial could be interpreted differently. 
Because of the wide variability in the data, and the lack of 
confirmation of antiviral activity by p24 antigen tests, one 
could conclude that the possible anti-HIV effect of curcumin 
in people has not been shown. The absence of p24 antigen 
reduction is surprising, since it was anecdotal reports of 
just such an effect, completely unexpected and unlikely to 
have been due to chance, that led to the curcumin trial in 
the first place. Some uncertainty will remain until other 
studies confirm or contradict these results.

Meanwhile, we note that the HIV RNA reduction was seen 
despite the fact that a number of circumstances probably made 
the response lower than it otherwise would have been.

First, this trial deliberately recruited persons with more 
advanced HIV disease, in order to get enough viral load for 
the p24 antigen test to measure. The data suggests that those 
with less advanced HIV infection might have responded better. 
(See discussion on viral suppression, below.)

Also, four of the 18 volunteers in this trial had 
opportunistic infections -- which can greatly increase the 
HIV viral load, by causing immune activation, which leads to 
the growth of HIV.

In addition, ten of the 18 volunteers received their flu 
shots during the trial. This probably affected the data; at 
least two research groups have reported that the immune 
activation caused by flu shots can temporarily raise the 
level of HIV RNA. Four patients received flu shots within 
three weeks of a measurement of HIV RNA, and all of them 
showed large increases -- about 10-fold for two of the four. 
This probably made the antiviral response to the treatment 
appear less than it really was. (Patient 7 received a flu 
shot one week before the blood draw which showed a very high 
value at week 8, contributing to the unusual data for week 8, 
which was discussed above.)

How do these results compare to what is known about other 
antivirals? Definitive figures are hard to obtain, since 
testing for HIV RNA is still experimental and fairly new; 
there is much variation within each test, and between the 
different tests. But it is generally believed that AZT will 
produce about a one log reduction (10-fold reduction) of 
viral load as measured by HIV RNA.

The best viral suppression so far has been with some of the 
new protease inhibitors, which can temporarily produce a 
reduction of viral load by two to three logs (about 100-fold 
to 1000-fold). New information is suggesting that even 
persons with very advanced HIV disease (for example, with a 
T-helper count under 10)  do show immune recovery and 
clinical benefit, if the virus can be suppressed enough. (At 
this time, unfortunately, that result can only be achieved 
temporarily, since HIV develops resistance to the drugs. This 
is why it is so important to test new drug combinations, such 
as one or more  protease inhibitors together with other 
drugs; in other diseases, such as tuberculosis and certain 
cancers, combinations of several drugs with different 
mechanisms of action have been successful in overcoming major 
problems of drug resistance. For the same reason, it is also 
important to test LTR inhibitors -- an approach not accepted 
at this time, nor even widely understood, in the AIDS 
research mainstream. If this kind of treatment works, it 
could become an important part of drug combinations.) 

It might not matter how the virus is suppressed, as long as 
it is kept low enough. This is why it is also critically 
important that better tests for viral load or activity become 
available for clinical practice. Then physicians will be able 
to tell quickly if a treatment regimen is working, or if it 
needs to be changed.

The SEARCH Alliance trial fits into this picture by showing 
the potential for developing an entirely new class of 
treatments -- drugs which target the LTR of HIV, not to kill 
the virus but to keep it inactive. Remember that curcumin is 
the weakest known agent of this class; it is attractive 
because it is widely available and relatively nontoxic, since 
it has long been used in food. But it may not be strong 
enough to help much by itself, especially  when HIV disease 
is already advanced. SEARCH Alliance is currently developing 
plans to test more powerful LTR inhibitors, such as beta 
lapachone, CPT-11, or topotecan.

Better HIV treatments are urgently needed. And a new kind of 
treatment would be especially important, by contributing to 
drug combinations which attack multiple targets of the virus. 
The SEARCH Alliance curcumin trial has provided the first 
human data on a new approach to AIDS drug development -- 
screening for compounds which inhibit the HIV LTR. While much 
more research is necessary, this trial has already suggested 
that the approach does work in people.

For More Information

For more information, contact SEARCH Alliance, 7461 Beverly 
Blvd., Suite 304, Los Angeles, California, 90036, 213/930-
8820.

Table I: HIV RNA Data

Patient#       week2  week4   week8  week12 week16  week20    CD4
      baseline                                             (baseline)
p01      180   4,000      1      70      5      10      10    344
p02   31,800 120,000 24,000   3,900     40   8,700 137,000    107
p03   86,300  20,800    400 120,000  7,800  27,600   2,700    133
p04      100     450      1     200     80       5     320    181
p05   28,500  13,300 12,400  25,000    530   6,000   3,700     78
p06   31,900  34,600  6,400   3,900    910   3,900   5,800    219
p07   15,000  41,000 14,000 150,000    900   7,000   3,700     15
p08   58,500  12,000    500     960  4,500   2,800   2,600     94
p09   38,400  18,000    200      88    890   9,100   5,000     46
p10   20,600  10,000    500     400     80   8,000     710    116
p11    1,854  61,500      1     270    800   3,000     850    391
p12   55,000  20,000      1  95,600 25,000  68,100  49,000     56
p13   78,400  46,900 16,000  25,200  1,400                     88
p14    2,500  15,400 10,000 130,000  8,000                     33
p15   13,700  25,000  1,000  83,900                           142
p16   21,800  52,100missing 180,000                           127
p17   16,000 100,000 11,800  76,100                            32
p18  100,000 45,590  25,000                                    10

** Figure I Data: [Note: Figure I to Figure III not included]

      baseline   week2   week4   week8  week12  week16 week20
Median   25150   22900    1000   25000     895    6500   3200
Count       18      18      17      17      14      12     12

** Figure II Data:

      baseline   week2   week4   week8  week12  week16 week20
Median   28500   18000     500     960     800    6000   2700
Count       11      11      11      11      11      11     11

** Figure III Data:

      baseline   week2   week4   week8  week12  week16 week20
Median   20600   25000     450    3900      80    3900    850
Count        9       9       8       9       7       7      7       

***** Resources: Important Articles

*** Protease Inhibitors: Current Status

"Protease Inhibitors: Overview and Analysis," by Dave Gilden, 
with assistance from Ben Cheng, Rick Loftus, and others, 
which appears in the March 1994 GMHC Treatment Issues, uses 
both published articles and unpublished information from 
within companies to provide an authoritative status report on 
the protease inhibitors now in human trials. This class of 
potential anti-HIV drugs is perhaps the most important group 
of experimental treatments at the present time, although the 
current candidates still face major problems -- including the 
development of resistant strains of HIV, poor oral 
absorption, and expense and difficulty of manufacture. The 
article reviews the drugs of Hoffmann-La Roche, Merck, Abbot, 
Searle (Monsanto), Vertex/Burroughs Wellcome, and Agouron; it 
also names a number of other companies which are developing 
protease inhibitors that are not yet in human trials.

To obtain a free copy of the March 1994 issue, write to: 
GMHC, Medical Information, 129 West 20th St., New York, NY 
10011.

[GMHC Treatment Issues is published 12 times a year; annual 
subscriptions are available for a suggested donation of $30 
individual, $50 physicians and institutions, and $60 foreign; 
persons with AIDS or HIV can contribute on a sliding scale or 
obtain a free subscription. You can ask to have your 
subscription start at the beginning of 1994, and include the 
special winter 1993/1994 issue on alternative treatments.]

Note: Dave Gilden, formerly a San Francisco-based freelance 
writer who often appeared in AIDS TREATMENT NEWS, recently 
moved to New York to become editor of GMHC Treatment Issues.

*** Drug Development: Interview with Roy Vagelos, Chairman of 
   Merck & Co.

"Roy Vagelos on AIDS Research and Drug Development," in the 
March 1994 GMHC Treatment Issues, examines a number of 
important areas from the viewpoint of perhaps the most 
influential person in the pharmaceutical industry. Dr. 
Vagelos is the chairman of Merck & Co., Inc., and the 
principal organizer of the Inter-Company Collaboration for 
AIDS Drug Development. Some quotes:

** "My opinion is that the cure, the real cure of any disease 
will come from an observation that may be totally unrelated 
to a focused applied program. And so the best thing that the 
government could do is to continue to stimulate the off-the-
wall types of research that come from people who are not told 
what do to. And people who develop real insight into 
following their own leads and their own hunches and are 
allowed to dream."

** "With AIDS, I am convinced that with persistence and 
probably a combination of drugs aimed at the enzymes that are 
now known we will be able to put together something that will 
control the infection."

** "What concerns me the most is that the Clinton health care 
reform proposal really puts our kind of work in great 
jeopardy. What they essentially would like to do is to have 
us invest and then at the end tell us what the price should 
be [and] determine what is reasonable. I just cannot see 
companies investing that kind of resources for that kind of 
time [with] the government at the end."

Dr. Vagelos also discusses how he would focus a national AIDS 
research program, and what kind of person he would put in 
charge. He expresses great confidence in Dr. Harold Varmus, 
the new director of the U.S. National Institutes of Health. 
He explains the difference between the kinds of focused drug 
development that pharmaceutical companies can do well, and 
the basic research and insight which is more likely to come 
from government-supported science.

The interview appears in the same issue as the protease 
inhibitor article, reviewed above. To obtain a copy, see the 
information above.

***** d4T Approval: FDA Advisory Committee Meeting, May 20

The Antiviral Drug Products Advisory Committee, a panel of 
outside experts convened by the U.S. Food and Drug 
Administration, will hold a public hearing on whether d4T 
(generic name stavudine, brand name Zerit) should be given 
accelerated approval on the basis of currently available 
data. The hearing, which includes times for public 
participation, is scheduled for 7:30 a.m. to 4 p.m. on May 
20, at the Parklawn Building, conference rooms D and E, 5600 
Fishers Lane, Rockville, Maryland. This committee will not 
make the final decision, but will make a recommendation which 
is almost always followed by the FDA. The committee is likely 
to vote on its recommendation at the end of the meeting that 
day.

Our understanding is that the developer, Bristol-Myers 
Squibb, will be asking for accelerated approval -- approval 
based mainly on the results of T-helper and viral tests, and 
given on the condition that additional research continues in 
order to obtain statistical proof of clinical benefit.

Comment

We have not seen the data which will be presented at the 
hearing, and therefore cannot take a position on whether the 
drug should be approved.

Some activists are concerned that the drug may be rejected 
even if the data is good, due to a more conservative make-up 
of the committee, and also due to general disappointment with 
the followup research after accelerated approval of ddC -- 
even though ddC was developed by a different company. If this 
happens, the fear is that, in effect, there will be no 
accelerated-approval mechanism left.

Other activists believe that certain possible side effects of 
d4T, such as sleep disturbances and depression, have not been 
adequately recorded. They are likely to ask that 
neuropsychiatric studies of any such effects be required as a 
condition for accelerated approval.

***** Acyclovir Over the Counter? FDA Hearing, May 19

The Antiviral Drug Products Advisory Committee will hold a 
public hearing on whether acyclovir should be switched from 
prescription to over-the-counter status. The hearing is 
scheduled for May 19 from 8 a.m. to 3 p.m., at the Parklawn 
Building, conference rooms D and E, 5600 Fishers Lane, 
Rockville, Maryland.

Comment

A major concern is that over-the-counter status will allow 
private and public insurers to refuse to pay for acyclovir, 
even when it is prescribed by a physician, making access 
difficult or impossible or some people. The price of the drug 
is expected to remain high, regardless of its prescription 
status, until rights to it expire in 1995.

***** AIDS TREATMENT NEWS Volume III Now Available

The new bound volume of AIDS TREATMENT NEWS is now available 
through our office, and will be in bookstores shortly.

Unlike our previous two volumes, Volume III is organized by 
subject, not chronologically. Therefore you can find all the 
articles on a major topic in one place. There is also a 
detailed table of contents, and an extensive, professionally 
compiled 23-page index. And throughout the book there are 
"January 1994" notes, to inform readers of new information 
available when the book went to press. (Volume III includes 
about 80 percent of the material published in AIDS TREATMENT 
NEWS from May 1991 through December 1993.)

Volume III also has a 42-page Resources section, much of 
which has never been published before in this newsletter or 
elsewhere. For example, it includes annotated lists of AIDS 
hotlines for general information, AIDS hotlines for treatment 
information, other specialized hotlines, AIDS newsletters, 
medical and healthcare books, how to obtain AIDS treatment 
information by computer, and lists of organizations; all 
phone numbers and other information was recently checked. A 
cross-reference lists AIDS information sources in Cambodian, 
Cantonese, Creole (Haiti), Dutch, French, German, Japanese, 
Korean, Laotian, Mandarin, Portuguese, Samoan, Spanish, 
Tagalog/Filipino, and Vietnamese.

The book is likely to be on the shelf in gay/lesbian 
bookstores, or in other bookstores which have a gay/lesbian 
shelf; the bookstore price is $14.95. Any bookstore can order 
the book through its distributor.

You can also obtain Volume III from AIDS TREATMENT NEWS; we 
have it in stock, available immediately. Send $21. (which 
includes first-class postage and handling) to: AIDS Treatment 
News, P.O. Box 411256, San Francisco, CA 94141; or you can 
order by phone, 800/TREAT-1-2, or 415/255-0588. (California 
residents add $1.08 tax. Orders outside of North America add 
$14 for air parcel post.)

Note: Volume III is now included when you order back issues. 
For back issues since April 1989, send $95 (California 
residents add $6.90 tax). This includes volume II, volume 
III, and all loose issues since volume III. (Volume I, April 
1986 through March 1989 and now mostly for historical 
interest and in limited supply, is available separately for 
$18, which includes postage and handling.)

Also, effective May 5, a copy of volume III will be included 
with any new subscription at the business/professional-office 
rate.

***** AIDS TREATMENT NEWS 
      Published twice monthly

Subscription and Editorial Office:
   P.O. Box 411256
   San Francisco, CA 94141
   800/TREAT-1-2  toll-free U.S. and Canada
   415/255-0588 regular office number
   fax: 415/255-4659
   Internet: aidsnews.igc.apc.org
Editor and Publisher:
   John S. James
Reader Services and Business:
   David Keith
   Thom Fontaine
   Tadd Tobias
   Rae Trewartha

Statement of Purpose:
AIDS TREATMENT NEWS reports on experimental and 
standard treatments, especially those available now. We 
interview physicians, scientists, other health 
professionals, and persons with AIDS or HIV; we also 
collect information from meetings and conferences, 
medical journals, and computer databases. Long-term 
survivors have usually tried many different treatments, 
and found combinations which work for them. AIDS 
Treatment News does not recommend particular 
therapies, but seeks to increase the options available.

Subscription Information: Call 800/TREAT-1-2
   Businesses, Institutions, Professionals: $230/year.
   Nonprofit organizations: $115/year.
   Individuals: $100/year, or $60 for six months.
   Special discount for persons with financial difficulties:
   $45/year, or $24 for six months. If you cannot afford 
   a subscription, please write or call.
   Outside North, Central, or South America, add air mail 
   postage: $20/year, $10 for six months.
   Back issues available.
   Fax subscriptions, bulk rates, and multiple subscriptions
   are available; contact our office for details.
   Please send U.S. funds: personal check or bank draft, 
   international postal money order, or travelers checks. 
   VISA, Mastercard, and purchase orders also accepted.

ISSN # 1052-4207 

Copyright 1994 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.