From: Billi Goldberg <bigoldberg@igc.apc.org>
Subject: ATN #165
Note: Copyright 1992, Dan R. Greening. Non-commercial reproduction allowed.
Archive-Number: 6658
Organization: unspecified
Date: Sat, 19 Dec 92 23:45:06 PST

&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& 
J O H N   J A M E S  writes  on  A I D S 
&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& 

Copyright 1992 by John S. James; 
permission granted for non-commercial use. 

AIDS TREATMENT NEWS Issue #165, December 18, 1992 
   phone 800/TREAT-1-2, or 415/255-0588 

CONTENTS:  [items are separated by "*****" for this display] 

Passive Hyperimmune Therapy:  Data Leaves Questions Unanswered 

Acyclovir Annual Price Cap for Some Patients, $2500; 
   Registration Required 

Reform of Federal AIDS Research Proposed to New 
   Administration, Congress 

New Software Available for Physicians' Offices and Community- 
   Based Research 

AIDS TREATMENT NEWS Selected Index Through 1992 

***** Passive Hyperimmune Therapy:  Unanswered Questions 

by Dave Gilden 

     In October the HemaCare Corporation of Los Angeles announced 
preliminary analysis of its completed 12-month phase I/II trial 
of passive hyperimmune therapy (PHT, also known as passive 
immunotherapy or PATH).  The blood products company claimed, in 
its statement and presentation at the National AIDS Update 
Conference in San Francisco, that the data confirm earlier 
indications of benefit (see AIDS TREATMENT NEWS #148, April 3, 
1992). 

     AIDS TREATMENT NEWS recently obtained from independent 
sources an unreleased, detailed statistical analysis of the trial 
data, performed by members of the University of California Los 
Angeles Department of Biomathematics.  That report raises 
questions about the completeness of HemaCare's summary 
description of the data collected so far.  Conclusions about 
PHT's long-term therapeutic value must await the findings of 
planned two-year phase III studies. 

     PHT aims to restore people's ability to control their HIV 
infections after immune deficiency has set in.  Patients receive 
monthly infusions of blood plasma pooled from asymptomatic HIV- 
positive individuals who are continuing to produce high levels of 
anti-HIV antibodies. 

     The data released by the company in October seemed 
promising. After a year on full dose PHT, volunteers who started 
with T-helper counts of 50 to 200 experienced an average T- 
helper cell loss of two per cent, compared to a 35 per cent 
reduction for those on placebo.  The benefit from PHT appeared to 
be dose-related:  Volunteers receiving half dose fell between the 
two values, with an average 25 percent T-helper cell loss.  Five 
deaths occurred on the placebo arm, three on the half-strength 
arm and one on the full-strength arm.  The company reported no 
significant adverse affects from the therapy, and no withdrawals 
because of toxicity. 

     While not questioning PHT's safety, the full statistical 
analysis presents a more confused picture than do the sketchy 
press releases.  Most of the trial volunteers yielding usable 
data -- 93 out of 155 -- had T-helper cell counts of less than 
50.  No significant benefits to volunteers with such low counts 
were detected.  This result conforms to a past study by Abraham 
Karpas, Sc.D., of the University of Cambridge.  Dr. Karpas' small 
study observed that the benefits of passive immunotherapy for 
people with people with ARC were much more long-lasting than for 
people with AIDS.  [See Proceedings of the National Academy of 
Sciences, USA, volume 67, October 1990, pages 7613-7617). 

     Joshua Levy, M. D., HemaCare's research director, told AIDS 
TREATMENT NEWS that the decision to focus on people with depleted 
T-helper populations was based on reasons of compassion as well 
as a desire to quickly obtain decisive data. 

     The positive findings HemaCare reported are based on 62 
individuals with T-helper counts of 50 to 200.  This small sample 
size reduced the possibility of obtaining clear-cut, 
statistically significant findings.  The full statistical 
analysis shows that average T-helper counts in the 50 to 200 
segment of the trial did jump upward in the first six months. But 
the one-year data are not as good:  T-helper counts on full dose 
in this group, up 33.7 percent above baseline at six months, had 
fallen back essentially to baseline by one year. 

     The trend in the second six months raises the question of 
how well PHT preserves T-helper cells in the long run.  An 
analysis carried out by the statisticians that gave greater 
weight to later T-helper counts revealed little significant 
treatment effect compared to the simple endpoint analysis 
HemaCare publicized. 

     As for survival rates, only a trend considered largely 
lacking in statistical significance was found when other factors 
were taken into consideration along with T-helper count.  These 
factors included AIDS or ARC diagnosis, weight loss and baseline 
p24 antigen level. 

     An unexpected problem is that original T-helper counts are 
missing for 29 of the 203 volunteers in the trial as a whole. In 
the full-dose PHT arm, the baseline T-helper counts are unknown 
for 5 of the 17 deaths.  This gap might have seriously skewed the 
results; adding just one more death to the full-dose, 50-to-200 
helper T-helper segment of the trial would alter the announced 
results considerably. 

     To get an independent view of PHT, we spoke with a staff 
member at one large AIDS clinic that is treating 30 patients with 
a passive immune technique similar in principle to PHT. According 
to this source, T-helper counts have not generally risen in 
treated patients, although skin conditions of all sorts have 
markedly improved.  This benefit could be due to other antibodies 
in the plasma as well as to the anti-HIV ones, the source 
observed.  He noted that enthusiasm for the therapy was waning at 
his clinic. 

     As was largely true in the HemaCare study, passive 
immunotherapy is being applied in this clinic as a rescue 
technique for people with T-helper counts under 50.  It is 
unclear what kills T-helper cells at this stage of disease. Their 
further loss may not be due to current HIV activity at all, but 
to immune dysfunction springing from past infection. Also, HIV in 
advanced AIDS is reproducing rapidly and therefore can mutate to 
escape neutralization by particular antibodies.  It would seem 
that passive immunotherapy's effectiveness would be limited under 
these conditions. 

     Michael Roth, M. D., is a Santa Monica immunologist who has 
had six years experience administering passive immunotherapy in 
his AIDS practice.  He thinks that the critical factor 
determining passive immunotherapy's effectiveness is clinical 
health.  Some patients who have near-zero T-helper counts but no 
history of opportunistic infections have remained stable and in 
good health for years on passive immunotherapy, he told AIDS 
TREATMENT NEWS. 

     Drs. Roth and Karpas both think that PHT and similar 
therapies would be most useful for extending the asymptomatic 
period by several years in persons with moderately affected 
immunity (T-helper counts of 200 to 400). 

     But it is difficult to test PHT's effectiveness in this 
group because of its members slow rate of decline.  HemaCare is 
now seeking a "treatment IND" from California's Food and Drug 
Branch (a state equivalent of the FDA) to try PHT in people with 
T-helper counts in the 200 to 400 range.  The two-year, open- 
label treatment IND will allow HemaCare to administer PHT and 
collect data at its four California infusion centers. HemaCare 
also will attempt to recover costs from patients' insurance 
companies.  (The company does envision some free distribution to 
those unable to pay.)  Meanwhile, a double-blind, two-year-long 
phase III trial involving volunteers with T-helper counts of  50 
to 200 will begin this winter if the FDB approves. 

     Over 100 volunteers from the phase II trial will continue to 
receive PHT.  This is important because one small French study 
indicated that discontinuing this therapy led to rapid 
deterioration in people with advanced immune deficiency.  [D. 
Vittecoq et al., Journal of Infectious Diseases, Feb. 1992, 
165(2):364-8] 

     HemaCare expects to be administering PHT to 900 people soon 
and is actively seeking donors with sufficient HIV-neutralizing 
antibodies.  Donors receive $25 per donation plus free blood 
tests. 

     A beneficial rebound effect from the periodic plasma 
withdrawals may raise donors' antibody levels, indirectly making 
passive immunotherapy of benefit to them, too.  In the completed 
HemaCare trial, about 90 per cent of regular donors maintained 
stable T-helper levels over the year.  According to HemaCare, 
donor data revealed a statistically significant, overall slight 
T-helper increase when analyzed by a method that controlled for 
other factors.  The meaning of such a result should be qualified, 
though, since there is no control group for purposes of 
comparison.  It is possible that any carefully selected group of 
individuals with high anti-HIV antibody levels would 
spontaneously show stable or even increasing T-helper counts 
whether or not they donated plasma. 

Comment 

     Tanya Youvan, M. S., HemaCare's PHT project manager, faxed 
us a five-page letter taking exception to some of the statements 
in a draft of this article.  She wrote that HemaCare has hired a 
new statistician to redo the analysis.  His report is due soon 
and, Ms. Youvan claimed, will provide most of the missing 
baseline T-helper counts.  Ms. Youvan also argued that the just- 
completed PHT trial was only a phase I/II study that was not 
supposed to provide conclusive efficacy data. 

     We welcome re-examination of the PHT data and further 
testing of this therapy.  But people with HIV are now making 
decisions about trying PHT and they need as much information as 
possible.  HemaCare's overly optimistic announcements of its 
trial results were made two months ago.  They claimed improved 
survival and statistically significant maintenance of T-helper 
cell levels on the basis of an analysis the company now feels it 
has to redo. 

     Ms. Youvan's objections did not touch two central points: 
(1) Average T-helper cell counts were not "maintained," but rose 
in the first six months and then starting falling.  By the end of 
the 12 month period, they were about equal to baseline in the 
50-200 T-helper group, suggesting that T-helper count increases 
may be temporary.  (2) The missing baseline helper T-cell data 
make the survival findings uncertain. 

     Ms. Youvan conceded that firm conclusions about who PHT 
benefits, and for how long, must wait for the larger study now 
being planned.  But we should not be too critical of the 
optimistic publicity HemaCare generated.  The blood-products 
company has taken on a very complex, neglected project beyond its 
normal area of expertise.  The need for prolonged testing has 
proved extremely costly to the company, which has had to cover 
the testing expenses through internal financing. 

     The focus on persons with low T-helper counts may have 
backfired, costing the company more in the long run.  It 
nevertheless was a valiant move on moral grounds.  It provided a 
plausible treatment alternative to people who had none, as most 
clinical trials exclude people with late-stage AIDS. 

     HemaCare in the past has been faulted for releasing its 
results through press conferences and other non-research forums 
(such as the National AIDS Update Conference).  It now promises 
to submit its findings in a peer-reviewed medical journal for 
publication -- which would help to resolve the remaining 
questions. 

***** Acyclovir Annual Price Cap for Some Patients, $2500; 
      Registration Required 

by John S. James 

     On December 7, Burroughs Wellcome Co. announced that it will 
cap the price of acyclovir (Zovirax) for patients who pay for the 
drug themselves.  Those who use more than 730 grams (for which 
Burroughs Wellcome charges wholesalers about $2500) in a single 
calendar year will receive up to 730 grams additional at no cost 
for the remainder of the year.  This program begins January 1; 
therefore patients who are using continuous high-dose acyclovir 
and paying for their own medication should immediately register, 
through their physician or other health-care provider, so that 
their acyclovir use can be monitored and credited toward the cap. 
Health-care professionals can call Burroughs Wellcome at 
800/722-9294 for more information about this program and how to 
register patients. 

     Unfortunately this program is only for patients who do not 
have third-party coverage for their acyclovir use. 

     The cost of acyclovir has become an issue, especially during 
the last year, because more people are using high doses 
continuously after a major study in Europe and Australia reported 
finding survival benefit in some patients.  (Youle, M. Double 
blind, placebo controlled trial of high dose acyclovir for the 
prevention of cytomegalovirus (CMV) disease in late stage HIV 
disease.  VIII International Conference on AIDS, Amsterdam July 
19-24, presentation number MoB 0056.) Most patients use acyclovir 
occasionally or temporarily.  But the new use can cost $5000 per 
year or more, creating severe financial hardship or making the 
drug unavailable to patients for whom it was prescribed.  The U. 
S. patent on acyclovir does not expire until 1997. 

     AIDS treatment activists from several organizations had 
negotiated with Burroughs Wellcome for ten months seeking price 
relief; according to Andrew Zysman, M. D., of ACT UP/Golden Gate, 
the company rejected an overall price cut but agreed to a price 
cap.  Activists were not told the amount of the cap, or that 
patients with third-party coverage for the drug were ineligible, 
until the day the program was announced to the press, so they 
were unable to advocate for important changes. 

     "There are two problems with the policy," said Dr. Zysman. 
"The cap, while a start, does not go far enough.  A workable 
solution would be an annual cap of $2000 per patient, which would 
continue to generate great profits, while making acyclovir more 
accessible. 

     "Second and most disappointing, the cap only applies to 
people without insurance.  Activists are concerned about the cost 
of AIDS care not only to uninsured individuals, but also to the 
bankrollers of health care in America, the government and private 
insurers.  Many physicians, for example in public health 
settings, are unable to suggest the use of acyclovir because it 
would bankrupt their clinic's budget; hence patients will not be 
able to benefit. 

     "We believe Burroughs Wellcome has made a grave error, 
acting neither in its own interests nor in the interests of the 
HIV community.  A lower price cap, applied to all patients 
irrespective of insurance coverage, would affect physicians' 
attitudes about the cost-benefit ratio of acyclovir, and would 
create more widespread usage, generating greater, not lesser 
profits for Burroughs Wellcome." 

     Dr. Zysman has heard that Burroughs Wellcome did plan for 
the cap to cover all U. S. patients, but that pharmacists' 
representatives argued that their prescription-monitoring 
software was not set up to track such use.  He also heard that 
activists were kept out of these negotiations because the company 
feared running afoul of regulations on the disclosure of "inside 
information" which could affect stock prices. 

     Note:  Burroughs Wellcome replied that it already provides a 
26 percent rebate to Medicaid, and effective January 1 will 
provide comparable discounts to state AIDS programs, sexually 
transmitted disease clinics, community and migrant health 
centers, homeless programs, public housing clinics, and mental 
health, tuberculosis, and family planning clinics. 

***** Reform of Federal AIDS Research Proposed to New 
      Administration, Congress 

by Keith Griffith 

     A reform package that could lead to significant changes in 
the way the federal government conducts AIDS research at the U. 
S. National Institutes of Health is being given serious attention 
by the Clinton transition team.  The reforms, which are still 
being developed before the convening of a new Congress in 
January, are viewed by proponents as critical if President-elect 
Clinton is to live up to his campaign rhetoric for a vastly more 
serious commitment to AIDS.  AIDS TREATMENT NEWS has learned that 
representatives from Treatment Action Group (TAG), AIDS Action 
Council (AAC), and Human Rights Campaign Fund (HRCF) have 
conducted high level meetings at NIH regarding the reform 
package.  These groups have also found significant support both 
on Capitol Hill and in the Clinton transition team. 

     The reform package, actually a series of 24 proposals, would 
centralize all AIDS research programs at NIH under the authority 
of the Office of AIDS Research (OAR).  "We want the OAR to have 
increased budgetary and administrative authority," TAG 
representative Gregg Gonsalves stated.  "Right now there are 21 
institutes, centers and divisions at NIH that supervise AIDS 
research, and we would like OAR to have a single budget line for 
themselves and to distribute money instead of going through 21 
directors who decide where it goes.  [The AIDS program at NIH] is 
a huge program, $1.2 billion.  If that were reorganized well, run 
more efficiently, with some sort of strategic vision for what 
they were doing, we would have reason for hope." 

     Gonsalves speaks confidently about the need to centralize 
AIDS research at NIH because earlier this year he and colleague 
Mark Harrington, both of TAG, conducted an exhaustive study of 
the NIH AIDS program (see AIDS TREATMENT NEWS issue # 156).  What 
they found was a billion dollar investment with no one in clear 
command.  In the study by Gonsalves and Harrington, they 
documented what many have suspected all along:  that NIH is 
plagued by gaps in research, that redundancy is far too common 
and that there is virtually no  strategic planning.  OAR, which 
was created by Congress in 1988 to oversee federal research at 
NIH, was never given enforcement powers to carry out its mission. 
The TAG report calls it all "an elaborate charade." 

     "OAR has no teeth at all," is the belief of Derek Hodel of 
AAC.  "The reforms we are circulating are designed to give OAR 
the teeth to do the job they were mandated to do in the first 
place:  to coordinate AIDS research, to devise a strategic plan 
with broad research goals, and to coordinate research among the 
NIH institutes."  This would be accomplished by giving one 
office, the OAR Director, authority to oversee budget decisions 
and enforce both short and long-term planning.  OAR would report 
directly to the NIH Director and would work with the newly 
created Special Assistant to the President on AIDS (frequently 
referred to as "AIDS Czar") to assure a continued pro-active 
stance from the White House. 

Will These Reforms Work? 

     The critical question, we think, is whether these reforms 
would actually make a significant enough improvement in the 
development of meaningful treatments, a cure for persons living 
with HIV today, and eventually a vaccine. Additionally, many 
scientists will wonder how these reforms will impact on them. 

     There has been little community discussion over these 
reforms recently since very few people are aware just how 
seriously they are being taken, now that the Bush Administration 
is on the way out.  This lack of public discourse is not because 
of some desire to hide these proposals.  It reflects the sad 
state of affairs regarding how few people are advocates for 
treatment research within the network of community-based 
organizations which deal primarily in AIDS care giving and 
prevention.  Nevertheless support is growing and supporters on 
Capitol Hill may place the reforms into legislation as early as 
January.  Senator Ted Kennedy and Congressman Henry Waxman are 
expected to include the package in bills that will also remove 
the ban on fetal tissue research and strengthen women's health 
research funding. 

     AIDS TREATMENT NEWS, looking to find expert opinion about 
whether this particular reform package could succeed in improving 
research at NIH, spoke at length with a senior professor at one 
of the nations most respected schools of public health.  This 
person, who did not wish to be identified, has significant 
experience working within large institutions engaged in 
protecting the public health.  Our source has had little 
experience in the field of AIDS research and was relatively 
unaware of the current situation at NIH. 

     After studying the reform package, we went through each 
proposal separately.  Concern was voiced only around issues of 
how some points would not likely be acceptable to a bureaucracy 
or to existing government hierarchies.  There was concern that 
the OAR Director would be in a position of advocating publicly 
against the policy of the Administration.  Another concern was 
voiced about the implications of creating a budget bypass 
(allowing OAR to report directly to the president on budgetary 
issues, rather than going through NIH; the National Cancer 
Institute at NIH has had a similar bypass since 1972), though 
there was agreement that oversight and enforcement of a budget 
would work better if direction comes from one office.  Even with 
these reservations, our expert source stated, "The idea of having 
an (OAR Director) who is in charge of coordinating across all the 
institutes and having a lead role in running various task forces, 
not only within the Public Health Service, but also outside, 
would be very healthy and helpful and I think ought to be 
possible." 

     Those pushing these reforms are in the process of winning 
scientific support, as well as seeking out diverse views about 
how to strengthen the existing package.  A large list of names, 
both in AIDS research and in other areas, has been assembled and 
will be consulted in the coming weeks.  Derek Hodel with AAC 
worries that some scientists might see these reform efforts as a 
way to interfere with what researchers can do in the lab.  "I 
don't think that our plan would impede the kind of creative 
thinking needed to fight AIDS," Hodel said.  "The types of 
direction we are looking for are very broad, thematic 
directions." 

     The reform package is coupled with a push for a fifty 
percent increase in federal spending on AIDS research in 1993. 
Activists believe the two together will provide the significant 
jolt needed to open up the pipeline to new research and speed 
along projects already in development.  Another crucial part of 
the strategy, being developed jointly by TAG, AAC, HRCF and 
others, will be obtaining the president's support.  One document, 
"Confronting HIV/AIDS:  Initiating Change," a 24 page outline of 
what is needed from the new Administration, which came out of a 
recent meeting of 75 community leaders convened by AAC, calls 
upon President-elect Clinton to deliver a major televised address 
to the nation on AIDS during the first 100 days of his 
Administration.  Hodel described what the President should do in 
such a national address, to add the sense of urgency needed as 
well as reforming NIH and providing additional funding.  "It is 
hard to know for sure, because we have never had presidential 
leadership, but I think in the case of AIDS, a signal from the 
President would do it.  If the President tells NIH, 'move this 
stuff,' it will happen.  President Clinton needs to say that AIDS 
research is a top-priority of this administration.  It needs to 
be that clean and that simple and that public a signal." 

***** New Software Available for Physicians' Offices and 
      Community-Based Research 

by John S. James 

     A medical-office and research software system, developed 
over the last five years by the nonprofit National Community 
Research Initiative (NCRI) in Washington, D. C., is now available 
for community-based research organizations and for medical- 
records management in physicians' offices and clinics.  The 
system, called Medsys*, is remarkably easy to use; it largely 
automates the maintenance of patients' charts, produces custom 
patient flowsheets on demand, and assists in other functions 
including prescriptions, laboratory, specialists and referrals, 
and scheduling. 

     In addition to its use in daily clinic management, the 
system supports research in several ways.  It keeps almost all 
patient data in a compatible, computerized form, so that records 
can be combined from different practices and clinics for 
retrospective studies.  It enables physicians with large HIV 
practices to quickly check all of their patients' records to test 
hypotheses as they come up -- usually prohibitively difficult 
with the usual paper-based medical records.  And it greatly 
reduces the work of identifying patients within a practice who 
are eligible for a prospective clinical trial. 

     Medsys has been tested in daily use in the practice of Larry 
Bruni, M. D., for about two years.  Dr. Bruni, the leader in the 
development of Medsys, has a large HIV practice, currently over 
1300 patients, in Washington, D. C. (An interview with Dr. Bruni 
on treatment strategies appeared in AIDS TREATMENT NEWS #124, 
April 5, 1991.) 

     This article will outline some of the highlights of the 
system, the computer environment in which it runs, and the 
business and practical arrangements to install it for community- 
based research, or for use in other clinics.  The next step for 
interested medical professionals is to talk to persons who have 
used Medsys, or to see a demonstration, which provides a better 
feel for the system than a printed article can, and a better 
sense of its potential uses and importance. 

System Overview 

     Medsys runs on a local area network of DOS (IBM-compatible) 
computers.  As many terminals as needed can be connected; they 
can be in patient examining rooms if desired, in physicians' 
private offices, where blood is drawn for laboratory tests, and 
in the reception or accounting areas.  (Passwords can prevent 
administrative employees from viewing patients' medical data.) 
In addition, physicians can access the system by telephone from 
home or while traveling, using portable computers, giving them 
complete access to patient records in an emergency, even during 
nights or weekends when no one is in the office. 

     To use Medsys, physicians or staff at any available terminal 
can select a patient by typing a few letters of his or her name, 
or by using a patient identification number if available.  The 
patient's name, address, demographics, and insurance information 
appears, and menus guide the user to appropriate parts of the 
electronic chart, including laboratory tests, radiology, 
pathology, problem list (of all current and resolved medical 
conditions diagnosed), medication list, and physical exam 
information.  Data can be added or changed, and a patients' 
medical history can be displayed immediately, in various tabular 
or graphic forms, either on the screen or on paper. 

     Many clinical laboratories now transmit results 
automatically by telephone to the offices of the physicians who 
ordered the tests.  Usually the results are printed on paper as 
they come in, but with Medsys they go directly into the database 
as well; no retyping is required.  (A person must intervene, 
however, before the data goes into the patients' charts. Since 
there can be incompatibilities or errors, such as slight 
differences in the spelling of a patients' name by the 
physicians' office vs. the laboratory, or notes to the physician 
from the laboratory, human examination is required to assure 
accuracy.  It takes only a few minutes a day to post the labs in 
Dr. Bruni's 1300-patient practice.) 

     Laboratory tests include chemistry panels, drug levels, 
endocrinology, hematology, immunology, microbiology, p24 antigen 
and antibody, serology, T-cell subsets, and urinalysis.  Some of 
these categories (such as chemistry and microbiology) have 
submenus which are selected for display or editing of the data. 

     Normal ranges for the same test (e.g. T-helper count) often 
differ between laboratories.  Medsys records the normal values 
for each test used in the clinic or physicians' practice, and 
marks high or low patient laboratory results to call attention to 
them.  New tests or new laboratories can be added, or existing 
values changed, by the physician's staff when necessary. 

     Patients' records also include the pharmacy at which they 
usually fill prescriptions, and formatting information for 
specimen labels, which are printed as needed by Medsys. 

     The problem list is kept by ICD-9 codes (International 
Classification of Diseases).  The ICD-9 directory is included in 
Medsys, so users can search it for keywords and do not need to 
have the printed volume available to look up the codes. 

     Usually data is entered by selection from lists (of 
diseases, medications, tests, findings, etc.), instead of by 
typing in text.  This system saves time, avoids spelling errors 
or incompatible synonyms, and facilitates research by helping to 
make the computerized data compatible between different 
physicians' practices. 

     When the physician decides on tests, specimen labels are 
automatically printed at the appropriate departments.  The system 
also computes the bill for the visit, which is usually ready by 
the time the patient gets to the front desk. 

     Not everything in the database is patient information. 
Other sections record consultants, pharmacies, hospitals (which 
works like "consultants," except that it also has menu choices 
for departments and staff, including the best persons and phone 
numbers to call during any shift), vendors, drugs and companies, 
services, and friends.  Another section keeps the appointments 
and other schedule information for physicians and staff. 

     Research and expanded-access protocols can also be entered 
into the system. 

     For research use, data can be transmitted (by telephone if 
desired) without patient identifiers to other sites, to be 
combined for community-based research.  Also, an interface 
between Medsys and SAS (a standard statistical analysis software 
package) is now being developed. 

Business Arrangements 

     Medsys was created by the National Community Research 
Initiative (NCRI), a nonprofit organization.  Medical Office 
Management Systems (MOMS), a for-profit corporation, sells Medsys 
commercially.  MOMS owns Medsys, while NCRI has an unlimited 
license for HIV research.  MOMS is also customizing Medsys for 
oncology and cardiology, which requires adding additional 
laboratory tests, and other minor modifications. 

     MOMS sells Medsys for $25,000, which includes installation 
and training; there is also a $2500 per year maintenance fee. 
This does not include the cost of the computers; usually these 
are ordered in advance, before the MOMS staff travels to the site 
for installation. 

     NCRI is providing Medsys free (except for the cost of 
computers and the maintenance fee) to HIV practices and clinics 
which support community-based research and agree to certain 
restrictions -- the main one being not to provide data collected 
through this software to third parties without the permission of 
NCRI. 

     MOMS is working with Curaflex, headquartered in Ontario, 
California, to set up a national network of community-based 
research sites which use the Medsys software.  The (anonymous) 
patient information from all these sites will be combined to 
quickly identify patients eligible for new clinical trials. 
Later, data from the trials will be sent to a biostatistical 
center for analysis.  Such a system has considerable commercial 
potential, since the FDA is moving toward earlier approval of 
drugs for life-threatening conditions, while requiring that more 
research be done in postmarketing studies.  Community-based 
trials, which are conducted through physicians' offices, are 
ideal for such studies, since the drugs are already in standard 
use and available by prescription.  Software such as Medsys 
should enable pharmaceutical companies to get answers faster and 
less expensively, when the FDA asks for particular information. 

Technical 

     For those interested in the system internals, Medsys is 
programmed in Foxpro, a commercially available database language, 
and uses the SQL query language.  The software is table-driven 
and easy to modify, which allowed its rapid evolution in Dr. 
Bruni's practice; when he wanted a change, the programmer could 
quickly provide it. 

     Recommended equipment for running Medsys is a 486 computer 
(it can run on a 386); a mouse is optional.  Medmodem*, the part 
of Medsys which controls the modem (for receiving laboratory test 
results, allowing remote access to patients' records by the 
physician, and sharing research data) can use a 286. 

     The computers are connected with a Novell local area 
network. 

Comment 

     Before publishing AIDS TREATMENT NEWS, this writer developed 
computer software, and was particularly interested in making it 
easy to learn and use.  In this respect Medsys has done very 
well.  Medical staffs are already oriented to the system before 
training begins, because they are familiar with its elements -- 
the individual patients in the practice, clinical and laboratory 
findings, medications, prescriptions, pharmacies and other 
vendors, specialists and consultants, calendars and appointments, 
etc.  At every point the screen shows what the user's options 
are, so it is seldom necessary to consult the manual. 

     And with proper hardware the system is fast, usually 
responding immediately to user choices, even with 1300 patients 
in the database in the practice where we saw the software 
demonstrated.  The benefit is not only in saving staff time, but 
also in allowing people to work at their own rhythms, instead of 
having to change to accommodate the computer. 

     We believe this system can contribute significantly to the 
computerization of medical records, which would greatly 
facilitate both retrospective and prospective community-based 
research. 

For More Information 

     For more information about the Medsys system, contact Peter 
H. Anestos, President, NCRI, Suite 201, 801 Pennsylvania Ave., S. 
E., Washington, DC 20003-2167, phone 800/466-0854. 

***** AIDS TREATMENT NEWS Selected Index 

Compiled through 1992 by Denny Smith and Thom Fontaine 

     This index lists selected topics from past issues of the 
newsletter which still seem relevant -- and obviously the more 
recent the issue, the more current will be the information. Note 
that the entries listed here will be found in the text of one or 
more articles in the issue(s) listed, but not necessarily in the 
table of contents.  

 TOPIC ISSUE NUMBER(S) 

 3TC   140 
 5-fluorouracil/5-FU   122, 129 
 566C80 (atovaquone)   123, 129, 133, 139, 160, 164 
 acemannan   157 
 ACT UP   146, 147, 165 
 activism   147,151, 164 
 acupuncture   130, 157 
 acyclovir (Zovirax)   83, 108, 115, 132, 133, 143, 165 
 adrenal glands   140 
 aerosol pentamidine   114, 129 
 AGM-1470 (see TNP-470) 
 albendazole   129 
 alpha APA   159 
 alpha interferon   87, 119, 122, 133, 154, 155 
 alternative treatments   153, 157, 158 
 amikacin   109 
 amphotericin B/liposomal AmB   117 
 Ampligen   119 
 anemia   82 
 angiomatosis   129 
 Antabuse (disulfiram)   132 
 anti-angiogenesis   117, 122, 135, 141 
 anti-idiotype antibody therapy   93, 110 
 antioxidant   152 
 antisense   141 
 antivirals   158, 164 
 aphthous ulcers   133 
 Asacol   109 
 aspirin   109, 118 
 atovaquone (566C80)   123, 129, 133, 139, 160, 164 
 azithromycin   113, 124, 132, 133, 136,139, 152 
 AZT(zidovudine,Retrovir)   143, 144, 145, 150, 154, 155, 158 
 bacillary angiomatosi   129 
 bacteremia   129 
 bacterial infections   120 
 Bactrim (co-trimoxazole, TMP-SMX)   114, 123, 129, 147, 152, 161 
 benefits   74, 76, 105, 144 
 beta carotene   134, 158 
 BHT   10, 71 
 BI-RG-587   117, 125, 127 
 biological response modifiers   120, 122 
 bitter melon   155, 157 
 bleomycin   122 
 blue-green algae (sulfolipids)   87, 99 
 breast cancer   145 
 buyers' clubs   143, 144, 145 
 cancer   122, 126, 135, 139, 162 
 candidiasis (thrush)   133 
 capsaicin (Axsain, Zostrix)   121 
 CD4 (recombinant soluble)   158 
 CD4-PE40   130 
 CD8 expansion   151 
 CDA (chlorodeoxyadenosine)   110 
 chemotherapy   122, 135 
 children/infants   120, 123, 124, 130 
 Chinese medicine   68, 126, 153, 158 
 chiropractic   130 
 cholera   152 
 Chronic Fatigue Syndrome (CFIDS)   132 
 cimetidine (Tagamet)   122 
 ciprofloxacin   152 
 clarithromycin   113, 124, 129, 137, 139 
 clindamycin   111, 129 
 clinical trials   116, 141, 142, 144, 149, 154 
 clofazimine (Lamprene)   141, 149 
 CMV   124, 129, 133, 138, 146, 149 
 coenzyme Q-10 (ubiquinone)   119, 124 
 cofactors   119, 124 
 colitis   133 
 combination therapies   115, 119, 145, 149, 150, 154, 155, 156 
 community research   105, 143 
 compound Q (trichosanthin)   119, 155 
 computer resources   114, 116, 124, 154, 165 
 cortisol   140, 150 
 CPFs   108 
 cryotherapy (liquid nitrogen)   122 
 cryptococcal meningitis   117, 129 
 cryptosporidiosis   95, 107, 111, 113, 124, 129, 133, 139 
 cytarabine(ARA-C)   129 
 d4T   158, 159, 161 
 dapsone   114, 125, 129 
 daunorubicin   117, 122 
 ddC   115, 132, 141, 144, 145, 149, 150, 154 
 ddC/AZT   115,132, 145, 150 
 ddI   125, 131, 137, 141, 149, 150, 160 
 dementia   97, 101, 156 
 desensitization   147, 161 
 dexamethasone (Decadron)   79, 88, 93 
 dextran sulfate   89 
 DHEA (EL 10)   140, 150 
 diagnosis accuracy   119 
 diarrhea   133,141 
 diclazuril (Clinicox)   107, 157 
 disability regulations   144 
 doctor/patient relations   100, 111 
 doxorubicin (Adriamycin)   122 
 doxycycline   119, 124, 129 
 dronabinol (Marinol)   131, 133, 141 
 DTC (Imuthiol)   114, 131, 132 
 eflornithine (DFMO)   94, 95 
 encephalitis   79, 97 
 endocrine problems   140, 150 
 enteritis   133 
 eosinophilic folliculitus   161 
 epidemiology   124 
 EPO (erythropoietin)   150 
 Epstein-Barr Virus (EBV)   93 
 erythromycin   129 
 esophagitis   133 
 etoposide (VP-16)   122, 149 
 exercise therapy   157 
 FAACTS   119 
 Fansidar   108, 114 
 fetal tissue research   164 
 FIAC   94 
 FIAU   129, 133 
 Flagyl (metronidazole)   129 
 FLT (fluorothymidine)   119, 145 
 flu shots   138 
 fluconazole (Diflucan)   129, 133 
 folic acid (folate)   134 
 foscarnet (Foscavir)   71, 83, 94, 108, 110, 129, 133, 136, 138 
 fumagillin   122, 135 
 funding/lobbying   97, 99, 145, 146, 151, 156, 157 
 G-CSF   122 
 gall bladder    124, 133 
 gamma globulin   119, 120, 124, 129, 152, 155 
 ganciclovir (DHPG, Cytovene)   108, 124, 129, 133, 138 
 gastritis   133 
 gene therapy   158 
 gentamicin   109 
 germanium   90 
 glutathione   88, 92, 93, 119, 121, 138, 141, 152, 157 
 glycyrrhizin   17, 103, 115 
 GM-CSF   122 
 gp120 (vaccine)   130, 149 
 gp160 (vaccine)   130 
 health care politics   120, 125, 126, 132, 135, 136, 137 
 hemophilia   102, 103, 132, 137 
 heparin, substitutes   122, 146 
 herpes/shingles   83, 115, 133, 138, 146, 149 
 HGP-30 (vaccine)   130 
 histoplasmosis   96 
 HIVIG (hyperimmune globulin)   148, 153, 154 
 HPMPC   149 
 human papilloma virus (HPV)   146 
 Humatin (paromomycin)   107, 111, 129 
 hydrogen peroxide   132, 134, 152 
 hypericin    91, 96, 117, 125, 138, 141, 146, 155 
 hyperimmune milk (colostrum)   49, 95, 107 
 hyperthermia   104, 122 
 ibuprofen (Advil)   109 
 idarubicin   122 
 IGF-1   146, 150 
 immigration politics   114, 120, 125, 128, 129, 134 
 immune globulin (IVIG)   119, 120, 124, 148, 152 
 immune restoration   151 
 immunomodulators   119, 151, 158 
 immunotoxins   140 
 Imuthiol (DTC)   114, 131, 132 
 indomethacin   109 
 insurance   120, 136 
 interferons   87, 101, 108, 114, 119, 122, 132, 151 
 interleukins   (IL-2, etc.)  119, 122, 151 
 international conference, Amsterdam   153, 154, 155, 156, 157,  
         158, 159 
 international edition, ATN   155, 159 
 international travel   128, 152 
 Iscador (mistletoe compound)   92 
 isoprinosine   106 
 ITP   48 
 itraconazole (Sporanox)   96, 161 
 IVIG   119, 120, 124, 148, 152 
 Kaposi's sarcoma (KS)   117, 122, 129, 135, 162 
 Kemron   97, 101, 114 
 ketotifen   158 
 L661 & L229   139 
 L671,329, L687,781   114 
 L697,639, L697,661   118, 125 
 labor unions   123 
 lacquered mushroom   157 
 laser treatments   75, 96 
 lentinan   19, 73 
 letrazuril   133 
 leucovorin   49, 52, 79, 108 
 levamisole   122, 124 
 lignins   158 
 liposomes   109, 117, 122 
 liquid nitrogen (cryotherapy)   122 
 lithium   119 
 liver problems   103, 133 
 Lyme disease   132 
 lymph tissue   153 
 lymphoma   93, 110, 136, 140 
 MAI/MAC   132, 136, 137, 139, 141, 149, 152, 158 
 marijuana   131, 133, 139, 141, 148, 156 
 Marinol   131, 133, 141, 148 
 mebeciclol   95 
 medical research funding   163 
 Megace (megestrol acetate)   133, 150 
 MEK   99 
 melanin   107, 139, 141, 144 
 Mepron (atovaquone)   123, 129, 133, 139, 160, 164 
 mexiletine   121 
 microsporidiosis   129, 133, 139 
 mitoxantrone   93, 122 
 molluscum contagiosum   133 
 monoclonal antibodies   129 
 mycoplasma   95, 108, 124, 129 
 myopathy   119 
 N-butyl-DNJ   149 
 N-of-one trials   153 
 NAC   88, 92, 93, 119, 121, 138, 141, 152, 157 
 naltrexone   16, 52, 119 
 National Commission   154 
 nausea   131, 139, 141 
 neopterin   86, 100 
 neupogen (G-CSF)   122 
 neurology   156 
 neuropathy   121, 130, 156 
 neuropsychiatric concerns   97, 101, 126 
 neutropenia   94 
 NIH, report on   156 
 nonsteroidal anti-inflammatories   109 
 nutrition/malnutrition   133, 134, 141, 152, 158, 163 
 octreotide (Sandostatin)   95, 127, 141 
 on-line computer systems   154 
 Oncolysin B   136 
 oral interferon   97, 101, 114 
 ozone   80 
 p24 (vaccine)   130 
 p24 antibody   100, 119 
 p24 antigen   100, 119 
 pain medication   154 
 parasites   133 
 passive hyperimmune therapy (PHT)   67, 92, 148, 149, 151, 158,  
         165 
 passive immunotherapy   67, 92, 148, 149, 151, 158, 165 
 pathogenesis   147, 156 
 patient/doctor relations   100, 111 
 PCR   62, 144 
 peliosis hepatis    129 
 pentamidine   114, 129 
 pentosan polysulfate   117, 122 
 pentoxifylline (Trental)   133, 145, 156 
 people of color   86, 99, 121 
 peptide T   84, 119, 126 
 Persantine (dipyridamole)   79 
 pets (infection hazards)   79 
 PF4 (recombinant)   122 
 pharmacies   64, 86 
 physician interviews   106, 119, 124, 126, 132, 135, 142,  
         143, 149, 160 
 piritrexim   122 
 PMEA   156 
 PML   115, 129, 153, 156 
 pneumocystis   114, 115, 123, 129, 139, 147 
 pneumonias, bacterial   119 
 policy   127, 136, 140, 146, 155, 156, 157, 158, 164, 165 
 polio vaccine   147 
 political funerals   157, 158, 160 
 polyadenylic polyuridylic acid   158 
 poppers   160 
 prednisone   150 
 pregnancy   90, 112, 153, 154 
 primaquine   113 
 prisons   106, 125, 126, 130, 149, 151, 161 
 probenecid   86 
 procysteine   152 
 programmed cell death (apotosis)   156 
 prophylaxis/prevention   114, 119, 123, 129, 158, 161 
 propolis   37 
 Prosorba column (protein A)   75, 122 
 protease inhibitors   117, 156 
 psychological health   161 
 PWA coalitions   117 
 pyrimethamine (Daraprim)   104, 108, 114, 129 
 R 82913   131 
 radiation therapy   73, 93, 110 
 recreational drugs   119 
 resource list   143, 144 
 reverse transcriptase inhibitors   117 
 ribavirin   141 
 ricin-A    140 
 rifabutin (Ansamycin)   149, 158, 160 
 rifampin   102 
 Ro 24-7429   141, 142, 153 
 roxithromycin   95 
 Salk vaccine (HIV)   98, 130 
 San Diego CRG   143 
 Sandostatin (octreotide)   95, 127, 141 
 scabies   98 
 SCH 39304   99 
 Septra (co-trimoxazole, TMP-SMX)   114, 123, 129, 147, 152, 161 
 shiitake   19 
 SP-PG   135, 141 
 sparfloxacin   129, 132, 152 
 spiramycin   79, 95, 107 
 stem cell research   151 
 steroids   114, 115, 133, 150 
 sulfadiazine   104, 108, 129 
 sulfolipids (blue-green algae)   87, 99 
 sunlight   58, 124, 161 
 superantigens   151 
 surrogate markers   119, 144 
 symptoms   100, 119, 124 
 syphilis   124 
 T4-helper (CD4) cells   119, 144, 147 
 tat inhibitors   127, 128, 132, 141, 142, 153 
 tests (blood values)   119, 144, 151 
 thalidomide   133 
 THF (thymic humoral factor)   151 
 thymopentin (TP-5)   123, 149    (and Jan. 1993) 
 TI-23   108, 129 
 TIBO derivatives   97, 131 
 TLC-G-65   109 
 TNP-470 (formerly AGM-1470))   135, 141, 162 
 toltrazuril (Baycox)   111 
 toxoplasmosis   109, 113, 123, 124, 129, 139, 152 
 TP-5   123, 149    (and Jan. 1993) 
 TPN feedings   133 
 transfer factor   47, 119 
 travel   152 
 treatment access   115, 116, 118, 119 
 treatment information sources   121, 162 
 treatment strategy   100, 111, 119, 124 
 trental   133, 145, 156, 158 
 tretinoin (Retin-A)   122 
 trifluridine (Viroptic)   115 
 trimetrexate/leucovorin   49, 52,79, 108 
 tuberculosis   106, 161 
 tumor necrosis factor (TNF)   88, 145, 156 
 ultraviolet light   161 
 vaccines   130, 149, 151, 152, 164 
 valley fever (coccidioidomycosis)   41, 96 
 Velban (vinblastine)   73, 122 
 vidarabine (Vira-A)   79, 94 
 vinblastine, vincristine   73, 122 
 viral quantitation   144 
 vitamin A   134, 152, 158 
 vitamin B   134, 152, 158 
 vitamin B-12   158 
 vitamin C   111, 152, 157, 158 
 vitamin D3 analogs   122 
 warts   112, 118, 146 
 women   90, 112, 115, 118, 130, 153, 154 
 yohimbine   159 
 zinc   134, 158 
 Zovirax (acyclovir)   83, 108, 115, 132, 133, 143, 165 

***** 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 
   415/255-4659 fax 
 Editor and Publisher: 
   John S. James 
 Medical Reporters: 
   Jason Heyman 
   John S. James 
   Nancy Solomon 
 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 1992 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. 

&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& 

Newsgroups: sci.med.aids