AIDS Treatment News
Retroviruses Conference Overview:
While little was surprising or revolutionary at this year's
4th Conference on Retroviruses and Opportunistic Infections
(January 22-26 in Washington D.C.), the work presented was
high quality and contributed solid advances in many fields.
This Conference is widely regarded as in many respects a very
successful one -- to the credit, of course, of the thousands
of researchers, who made more progress in 1996 than in any
previous year of the epidemic.
The meeting had its problems as well. Most people with HIV who wanted to attend were barred from this meeting (see article below). And some areas, such as nutrition, were largely absent. The rejected abstracts may be as important a story as any other from this meeting, but it is hard to learn about them because no list is available. This Conference reflected one particular group's vision of scientific quality and prestige.
Here are some of the central messages which we took away:
AIDS Treatment News will publish more detailed reports in separate articles on these and other results.
by John S. James
AIDS Treatment News will continue to summarize presentations
from the Retroviruses conference, but more detailed and
technical information can be found elsewhere, especially
through the Internet.
One of the best in-depth sources of information about the Conference is the Web reporting of Healthcare Communications Group, http://www.healthcg.com. Each night a team of leading AIDS physicians and treatment writers summarized major presentations from the day before, creating extensive reports which healthcare professionals can use for CME (continuing medical education) credit. The writing is aimed at physicians, and is often difficult for those without some background in AIDS treatments. This reporting was published despite strong opposition of the Conference organizers (the Steering Committee of the Scientific Program Committee).
For excellent reviews of treatment developments, at a less technical reading level, see the Project Inform site, http://www.projinf.org/RetrConf.
Other useful sites, all of which have different material, are:
The American Medical Association, http://www.ama- assn.org/special/hiv/retrocon.htm. This has links to the Healthcare Communications Group site and to the official Conference site (see below). It also has relevant news releases, and essays by experts.
The Body ("an AIDS and HIV resource"), http://www.thebody.com/retro197/retro197.html, includes reports on the Conference by Andrew Pavia, M.D., and Ramon (Gabriel) Torres, M.D. Also, it allows you to ask them questions electronically; the questions and answers are then posted for public access.
The International Association of Physicians in AIDS Care has a series of reports from the Conference which were written for its journal. Its site is at http://iapac.org/conferences/aidscan3/preliminary.html.
The National AIDS Treatment Advocacy Project, http://www.aidsnyc.org/natap, has reports focusing on protease inhibitors.
The official site of the Retroviruses conference, www.retroconference.org, includes only about a third of the talks which were given. It does have many of the slides shown in those talks, the only place the slides are generally available. The talks themselves are in audio, not in text; one can select a slide and hear the part of the talk which goes with it. The published abstracts of the talks are also available on a different page of this site, with a search function to find all abstracts which contain a certain word (e.g. the name of a drug). Unfortunately, the address of the abstracts page has been changed from time to time, apparently to prevent other sites from linking directly to the abstracts (and bypassing the Conference's home page and survey); this means that a "bookmark" (for easily getting back directly to the abstracts later) may not be reliable; it is better to bookmark www.retroconference.org, and go through the introductory pages and survey each time. Also, one is likely to encounter technical problems before successfully using the audio and slides.
Immunet (http://www.immunet.org) is preparing a page to link to all of the sites reporting on the Retroviruses conference; it should be ready within a week.
Low Vitamin B-12 Blood
by John S. James
A study at Johns Hopkins University, in over 300 men in the
Baltimore MACS cohort (Multicenter AIDS Cohort Study), found
that those with an abnormally low level of vitamin B-12 in
their blood serum progressed to AIDS almost twice as fast as
those with a normal level. This result was first presented as
an abstract at the XI International Conference on AIDS at
Vancouver1 last July, and was published in detail in the
February 1997 issue of JOURNAL OF NUTRITION.2 It was not
submitted to the Retroviruses conference. This study was
funded by two grants from the U.S. National Institutes of
The study did NOT find evidence that additional vitamin B-12 serum levels (beyond that necessary to avoid a deficiency) were associated with additional benefit.
The analysis was done retrospectively, by analyzing stored serum samples after a followup period of about nine years. Therefore, it is impossible to know whether the low levels caused the faster disease progression, or occurred as a result of it; a randomized trial would be needed to be sure that correcting an abnormally low level will improve a patient's prognosis. But the researchers suspect that the low levels were causing disease progression, not vice versa, for various reasons -- including the fact that the relationship was found even in the healthiest patients at least three years before development of AIDS, who presumably would have been least likely to have low blood levels as a result of the disease.
In contrast to vitamin B-12, serum levels of vitamin B-6, or of folate, were not found to correlate with disease progression in this study.
The almost two-fold increase in progression to AIDS in those with low B-12 levels was found "after adjusting for HIV-1- related symptoms, CD4+ cell count, age, serum albumin, use of antiretroviral therapy before AIDS, serum folate concentration, and frequency of alcohol consumption . . . Therefore, serum vitamin B-12 concentrations seem to be an early and independent marker of HIV-1 disease progression."
Note: An earlier study by the same Johns Hopkins group,3 which found greater survival associated with vitamin B-6 and several other micronutrients, was different because it estimated nutrient intake based on food questionnaires. It did not measure blood levels. (See AIDS Treatment News issue #214, January 6, 1995).
GS 840 (Adefovir Dipivoxil):
by John S. James
The Community Program for Clinical Research on AIDS of the
U.S. National Institutes of Allergy and Infectious Diseases
is seeking over 2,000 volunteers for a phase III trial of GS
840 (also called adefovir dipivoxil, or bis-POM PMEA), a drug
being developed by Gilead Sciences of Foster City,
California. The trial, being run through the offices of
hundreds of physicians and clinics in 16 U.S. cities, will
test whether the drug, taken orally once a day, can increase
survival of persons with advanced HIV, and also whether it
can prevent the development of CMV disease. A similar trial
will be run in Europe and Australia.
Volunteers need to have a CD4 count less than or equal to 100, and be in reasonably good health ("not require considerable assistance and frequent medical care"). They can be using almost any medication, except for permanent or maintenance use of CMV treatments such as ganciclovir or foscarnet.
GS 840 is an oral prodrug of PMEA, meaning that it is changed into PMEA in the body. PMEA itself has long been studied as an antiviral, but is less practical as a drug because it must be given by injection. In this study, participants will continue their regular antiviral treatments, and add GS 840 (120 mg) or placebo once a day; the nutrient L-carnitine will also be given (to both the drug and placebo groups), at the request of the FDA, since GS 840 has been found to lower L- carnitine levels in the body.
GS 840 is known to be active against CMV, hepatitis B, HHV6 (human herpes virus 6), and Epstein-Barr virus. It has shown modest activity against HIV, with about a 0.6 log decrease in viral load. Resistance seems to be slow to develop, and the drug is active against many viruses which have become resistant to other drugs. Unlike most available HIV treatments, it is believed to be active against HIV in macrophages as well as lymphocytes.
The informed consent for this trial lists its five purposes:
Bis-POM PMEA has been studied in more than 200 HIV-infected subjects who had a CD4+ cell count of 100 or more. Most of these subjects were not taking other drugs to treat HIV infection and were able to tolerate taking bis-POM PMEA.
Because much is unknown about how this drug will interact with treatments the volunteers are already using, the first 400 persons in this trial will be entered into a special safety-and-virology cohort and receive intensive followup. Also, the first 400 must be CMV positive by a blood test; later volunteers can be either CMV positive or negative.
For more information about this study, including participating physicians and clinics in your area, call the AIDS Clinical Trials Information Service, 800-TRIALS-A, between the hours of 9 a.m. to 7 p.m. Eastern time, Monday through Friday; ask for information about trials of GS 840 (or adefovir dipivoxil). Or call Gilead Sciences Medical Information, 800-GILEAD-5 (press 3), from 8:30 a.m. to 5:00 p.m. Pacific time.
A 134-page report on the current state of diagnosis,
treatment, prophylaxis, and research on more than a dozen of
the most common opportunistic infections was released January
1997 by the Treatment Action Group (TAG). It is edited by
Michael Marco and Mark Harrington of TAG, with an
introduction by William G. Powderly, M.D., principal
investigator of the AIDS Clinical Trials Unit at Washington
University Medical School in St. Louis. Both approved and
experimental treatments are covered.
The opportunistic infections addressed are:
Certain patients with herpes lesions which do not respond to
acyclovir are eligible for expanded access to topical
cidofovir gel. Cidofovir -- formerly called HPMPC -- is
active against many viruses and is currently approved for
injection use in treating CMV retinitis in persons with AIDS
(under the name VISTIDE(R), or cidofovir for injection). In
January 1997 Gilead Sciences applied to the FDA for approval
to market a gel formulation, under the name FORVADE(TM), and
announced a pre-approval expanded access program for this
To be eligible for this program, patients must have mucocutaneous herpes simplex infection unresponsive to at least a ten-day course of treatment with acyclovir. They must be over 13 years of age, and must not concomitantly use drugs with anti-herpes activity, or use other topical medications for the lesion. There are some other inclusion/exclusion criteria.
For more information about this program, patients should have their physician call Gilead Sciences Medical Information, 800-GILEAD-5 (press 3), from 8:30 a.m. to 5:00 p.m. Pacific time.
Protease Inhibitor Failures:
A Web site for both users and prescribers of protease
inhibitors has been set up to collect reports of failures of
"We are collecting stories from people who have failed protease inhibitors, or who have had unusual responses to the drugs. 'Unusual responses' would include the following:
"Users who wish to report serious side effects are also welcome to report their experiences, although this is not a focus of this project.
"For more information, contact Rick Loftus, 415/695-3818, Rick_Loftus@quickmail.ucsf.edu."
The Web address for this project is: http://www.netcom.com/~protease.
Non-Approved Liver Treatments:
AIDS Treatment News is collecting reports of first-hand
experience (positive or negative) of "alternative" (not
recognized by U.S. mainstream medicine) treatments for liver
problems -- such as glycyrrhizin (from the licorice plant),
silymarin (from milk thistle), alpha lipoic acid (also called
thioctic acid) and others. This information could be used to
help design a clinical trial to see if any of these popular
treatments have measurable benefit.
If you have information, contact Denny Smith, AIDS Treatment News, P.O. Box 411256, San Francisco, CA 94141, or fax to 415/255-4659, or email to email@example.com. Or call 800/TREAT-1-2, and leave the number and time best to reach you.
by John S. James
At least 15 security guards, some flown in from San
Francisco, blocked about 15 people with HIV who came to the
Sheraton Washington Hotel in Washington, D.C., hoping to
replace last-minute no-shows and attend scientific and
treatment discussions at the 4th Conference on Retroviruses
and Opportunistic Infections (January 22-26). Guards also
threatened to expel or arrest persons distributing flyers to
Conference participants or the press asking that future
conferences be open to those with HIV -- or informing
activists of a post-conference meeting to discuss a national
strategy to address growing problems in expanded-access
programs. Conference organizers did provide open video feed
(without badge checks) from only one of often five
simultaneous sessions, as well as allowing access to the
poster hall when posters were available for viewing but not
Apparently the security was hired to deal with several individuals who often disrupt AIDS meetings in San Francisco, where security at AIDS forums is now routine; the guards knew some of those people by name, and presumably were chosen because they knew their faces and tactics. But none of them showed up in Washington. No one came to disrupt the Retroviruses conference, so the expensive security only stopped people with HIV seeking medical and scientific information. (For background on the San Francisco disruptions, see AIDS Treatment News issue # 244, April 5, 1996.)
The official waiting list of researchers and physicians who also were denied attendance was approximately 500, but it is clear that many more people wanted to attend but were unable to. Some of the nation's leading AIDS research physicians -- as well as the Chair of the Presidential Advisory Council on HIV and AIDS -- were among those who tried to go but could not get in. Some applicants never heard back after they faxed their initial application -- and unless they called within about two days of the official opening date and learned that there was no record of their application, and that they had to send the paperwork again, it was usually too late.
One of the many press restrictions was that faxed newsletters reporting from the Conference with pharmaceutical-company support were prohibited. The International Association of Physicians in AIDS Care -- threatened with having its writers and staff banned from future conferences -- in the last week had to cancel its plans for daily reporting to its member physicians, at considerable cost to the organization. This affected many physicians, whose patients ask about treatments that are in the news; without daily medical reports from an ongoing conference, it can be hard to get in-depth information quickly.
The annual Retroviruses conference was started at the request of Federal agencies (the National Institutes of Health, and the Centers for Disease Control and Prevention), and has in fact become the U.S. national AIDS conference. As far as we can tell, all decisions regarding arrangements for this year's meeting were made by a four-person Steering Committee (which is within the Scientific Program Committee): Douglas Richman, M.D., chair; Constance Benson, M.D., vice chair; Chip Schooley, M.D., last year's chair; and Melissa Sordyl, M.B.A., executive director of the IDSA (Infectious Diseases Society of America). The rationale for limiting attendance was stated by Dr. Richman as the first words of the Conference:
"Before we start the program, I'd like to make a few remarks about the principles of this meeting. The Program Committee, in the design of this meeting, (wanted) to have a forum put together by basic and clinical investigators for basic and clinical investigators to present and exchange information, and with that objective in mind, the program committee confirmed -- by a very large proportion of the participants over the last three years -- (that they agreed) to keep it a meeting of this size and not expand it. . . The cost of that has been a (meeting) limited in size, and with some frustration, obviously, to some people, but there's always a trade-off between having a meeting of unlimited size with all of the circus-related activities that we've come to experience with some of the larger meetings, and something of this size. . . "
The four-person steering committee and others met privately on January 24, and is rumored to be inclined to enlarge the Conference by 1,000 to 1,500 additional people next year, although no official decision has been made.
At least four organizations or coalitions have started, or
are considering, legal action to prevent a repeat next year
of what happened at this Conference. Federal laws regarding
disabilities, and regulations on closed meetings and
dissemination of publicly-funded research, are being
Comment: Access to InformationMost activists involved with this Conference find it unbelievable that in 1997 people with HIV are fighting for access to scientific meetings, an issue which otherwise had been resolved years ago. The situation is widely seen as a serious threat to the partnership between persons affected and the research community -- a partnership firmly in place since 1990. AIDS treatment activists have made immense contributions to developing clinical trials that can recruit volunteers and otherwise work in the real world, greatly speeding drug development. They attend scientific meetings not only to get information, but also to raise questions, and to get researchers to interpret data in terms of what it means for people's care. If persons with HIV are not allowed to be full partners in the research effort, they cannot just walk away, because their lives are at risk. If partnership is denied, the relationship will shift from teamwork and support of research funding, to seeking information access through Federal rules, Congress, and the courts.
We believe that activists should avoid a negative focus on this particular meeting, by looking beyond it to the larger problems of medical information dissemination in an epidemic (including the Retroviruses conference). The system is not working. A current example concerns CPCRA 006, a study comparing daily vs. three times a week pneumocystis prophylaxis. This study, the largest controlled trial ever in AIDS, was surprisingly rejected from presentation as a "late breaker" at the Retroviruses conference. As a result, it was blacked out of all public and most private conversation at the Conference, where experts lectured on pneumocystis and its prophylaxis without mentioning the new information. Because of a U.S. Division of AIDS policy against releasing summaries before peer review, the results of CPCRA 006 might not be published until the ICAAC conference, September 28 - October 1 in Toronto. (Conferences such as ICAAC, or the Retroviruses meeting, are minimally peer reviewed in that presentations, submitted as abstracts, can be rejected. Journal peer review is usually more extensive, because the entire article is submitted and the reviewers can ask for changes, instead of only being able to accept or reject.)
Unfortunately it has become almost routine for information of medical and public-health importance, obtained with public funds, to be kept secret from the public and from most physicians. (Another major example is the International AIDS Society treatment standards, delayed for months before their release on July 10, 1996 when they were already largely obsolete.) This semi-secrecy, ostensibly to keep publication standards high and avoid misleading the public, really serves to increase the sales and prestige of scientific and medical journals by putting them at the center of national publicity when important news breaks; otherwise, there would be little objection to releasing the information during or after review, but before publication of record. Researchers cannot take the lead in correcting these abuses, because they fear retaliation when their own work is considered for publication.
But activists could blow the whistle. It is usually easy to confirm the existence of withheld information, given a detailed tip, even an anonymous one -- and usually dozens of people, sometimes hundreds, know enough to provide the tip. If there were a high-profile organization addressing this problem, anyone who knew about wrongful or questionable withholding of information important for public health would know whom they could write or call, at no risk to themselves. (For an example which already happened, note the recent press leak of the two-thirds drop in AIDS deaths in British Columbia during the last two and a half years; see "1997 Outlook," AIDS Treatment News #263, January 17, 1997. This information, important worldwide for treatment reimbursement and access to care, could otherwise have languished indefinitely awaiting publication -- although it is hard to see how peer review could much improve a simple report of a two-thirds drop in death rates.)
Another approach would be to investigate whether the current system of "information purgatory" -- major medical and scientific advances produced with public funds but withheld from the public for months -- provides unfair advantages to companies and investors with the right connections, creating a trade in private favors. Does this help to explain why a clearly dysfunctional system has been so resistant to change?
But the first steps should not be confrontational, but rather
to work with researchers, physicians, publishers, and others
concerned about medical care and effective information
dissemination, to devise a system which better serves the
public interest. A mechanism of rapid peer review followed by
Internet or online-journal publication (to avoid the weeks or
months of wait for physical page space) -- and which would
count as peer-reviewed "publication" in Medline and elsewhere
-- would be a major step forward. Meanwhile, activists can
support researchers who want to release their findings more
quickly, but are not in a position to advocate for a more
For More InformationShortly before the Conference, a coalition of major AIDS organizations, including the AIDS Action Council, AIDS Project Los Angeles, AIDS Research Alliance, Gay Men's Health Crisis, Linda Grinberg Foundation, Project Inform, San Francisco AIDS Foundation, and Treatment and Data Committee, began a campaign to persuade the Conference organizers to move the meeting to a larger location next year. On January 22 they released a five-page press background statement focusing on the issues of physicians and researchers excluded. During the Conference, several press releases from several individuals and organizations addressed the importance of access to persons with HIV; and the Conference organizers replied with their press release. A consensus statement calling for a more open meeting is also being drafted, but is not finished as this issue goes to press.
Also see "Strange Bedfellows Damage CDC and NIH Credibility," a strongly worded editorial in the February 3 issue of AIDSWEEKLY PLUS, an AIDS newsletter published since 1985, which was denied access to report on the Retroviruses conference.
For an information packet -- or to connect with other people who want to work on these issues -- contact either: Gary Rose, AIDS Action Council, 202/986-1300 x3026 or fax 202/986- 1345; or the Linda Grinberg Foundation, 310/471-4108 or fax 310/471-4565.
Note: Before publishing this article, we faxed a draft to the Steering Committee, asking for their comments about any facts in dispute, or other changes they might suggest. The Committee replied that "there are several inaccuracies in your story, particularly related to access to information, security, policy decisions related to the Conference, fax newsletters, registration for the Conference, and distribution/publication of new information in late breaker abstracts not accepted for presentation." The reply did not specify which of our statements were considered inaccurate, nor did it suggest any corrections or changes that we could make to meet their approval. We may publish a longer statement from the Steering Committee in the future.