AIDS Treatment News #158, September 4, 1992
John S. James

Each year these published-only abstracts from the international conference include important information, but are largely ignored. The reports are important, even though they did not make the cut as oral talks or as posters, because with something as rapidly changing and poorly understood as AIDS, no one, including the reviewers who selected the abstracts, can know what will prove valuable in the future; the most innovative leads, being unfamiliar, can end up in the published-only book. (We also noticed a number of high-tech research reports from Moscow in that volume. They may have missed a higher rating because reviewers had difficulty in evaluating them, since in the past there has been limited communication between AIDS researchers in the former Soviet Union and elsewhere, due in part to deliberate U. S. policy.)

Another reason why the published-only abstracts are largely ignored is that they are not tied to anything happening at the international meeting, while thousands of other abstracts are; conference attenders naturally read the latter first, to make sure they do not miss an important talk or other event. Therefore the scheduled presentations get most of the attention, and the total amount of information is so overwhelming that few have time get to the published-only papers.

This article summarizes some of the published-only abstracts in "Track A: Basic Science," one of the four tracks of the conference. We focus here on leads for new drugs or unfamiliar drugs, but could not finish even this category, and will have to continue this article in a future issue of AIDS TREATMENT NEWS. We also plan to look at the other tracks in future articles - especially "Track B: Clinical Science and Care." Note that all these abstracts were due March 2, 1992, so they do not include results after February.

Since Track A, which we are covering here, focused on laboratory research, the potential drugs mentioned are seldom treatments which are ready to use now; rather they are possibilities for the future. Although they do not have immediate use, physicians, scientists, and activists may find it helpful to know about them.

* "Ketotifen Inhibits the Production and Secretion of TNF-Alpha in PBMC Cultures of HIV-Infected Patients," Maria Ballmaier and others, Medical School Hannover, Germany, abstract # PuA6009. This paper found anti-HIV activity of ketotifen (an anti-asthma medicine used in Europe) at a concentration which could be achieved in patients. The mechanism of action is by reducing levels of TNF (tumor necrosis factor), which is similar to the action of the prescription drug pentoxifylline (see AIDS TREATMENT NEWS #156, pages 4-5), and possibly NAC.

* "Anti-HIV-1 Activity of CD4 Synthetic Oligopeptides," P. M. Cereda and others, University of Pavia, Italy, abstract # PuA6031. Two peptides which corresponded to a critical region of the CD4 molecule were found to inhibit HIV in laboratory tests. The abstract did not say how much inhibition was found. The principle here would be similar to that of soluble CD4, which in its original form failed to work as a drug in human tests.

* "The Experimental Investigation on Traditional Chinese Medicine for Anti-AIDS," Guan ChongFen and others, Institute of Basic theory of TCM, Beijing [abstract # PuA6068]. This abstract reported two separate studies. In one, "some Chinese herbs which were selected from effective clinical treatment in some African countries" were tested for antiviral activity against SIV (simian immunodeficiency virus, which causes an AIDS-like disease in some monkeys and which is very close to HIV-2) in laboratory tests. They did find a "significant" antiviral effect. The herbs were not identified.

The other study, in immune-suppressed mice, found that different herbs behaved as immunomodulators. They were identified only as "some prescriptions and herbs of effective clinical treatment, such as 802, 806, 809, 8911."

* "Effects of Immunomodulator SB-73 on Intra-Ocular Graft Tooth Germ Development," Sebastiao Hetem and others, School of Dentistry of Aracatuba, Brazil [abstract # PuA6072]. SB-73 is a potential AIDS treatment being developed in Brazil; a test in patients was reported at the international conference in Florence in June 1991 [Nunes and others, abstract # WA1238]. This study, a toxicity test in animals, found no problem with high doses. (Another abstract on effects of SB- 73 on tooth germ development was published in the same book, # PuA6159.)

* "Group Specific, Neutralizing, Syncytia Inhibiting, Cytotoxic Human Monoclonal Antibodies Against HIV-1 for Passiveimmunotherapy," Hermann W. D. Katinger and others, Institute of Applied Microbiology, Vienna, Austria [abstract # PuA6084]. Passive immunotherapy against HIV today is usually done by transfusing plasma from persons who are making good anti-HIV antibodies and remaining clinically well, to others who are not making antibodies effectively and are more seriously ill. A refinement of this method is the drug called HIVIG, in which the antibodies are extracted and purified from the blood of donors. In both cases, the antibodies were made by people.

It is widely agreed that the future of passive immunotherapy will depend on antibodies created by special cells engineered from human cells in the laboratory, allowing mass production of the antibodies and avoiding the need for human donors. Abstract PuA 6084 reported the development of 32 different cells which secrete anti-HIV antibodies; these were produced by finding cells which produced effective antibodies, then transforming those cells so that they could grow indefinitely. Three of the 32 cells were selected for human testing of the antibodies they produce.

(Note: We find it surprising that this abstract was not given a poster. This example illustrates the fact that there is no known rational way to select among five thousand abstracts in hundreds of different fields. We believe that this problem will only be solved by distributing the submitted abstracts in computer form, in such a way that they can be viewed through a user-changeable filter based on the evaluations of the referees. We suggested such a system and gave some details in AIDS TREATMENT NEWS #102, May 4, 1990.)

* "Retrogen Increases the Anti-HIV Activity of AZT, ddI, and ddC," by Erik De Clercq and others, Rega Institute, Leuven, Belgium, and Paul Ki, Retrogen Medical, Inc., Creston, Iowa [abstract # PuA6087]. Retrogen is "a double- stranded RNA conjugated with polysaccharide"; according to the abstract, it has been found to be not toxic to humans and to increase T-helper and white blood counts. In this study, it was tested in laboratory cells, using an animal virus (marine sarcoma virus), not HIV. A concentration of retrogen which gave 30 percent protection was able to reduce the effective concentration of AZT, ddI, and ddC to about a quarter of the concentration otherwise required. Retrogen was also tested against HIV and HIV-2, and the effective concentrations were found to be less than two micrograms per ml.

* "Booby Trapped Cells: A New Approach for Gene Therapy of HIV Infection," D Klatzmann, Hpital de la Piti- Salptrire, Paris [PuA6088]. Since the blood cells infected by HIV are all derived from stem cells in the bone marrow, it might be possible to genetically engineer some of these cells so that they could not be infected with HIV, allowing the patient's blood to be repopulated with new cells which are immune to the infection; this concept is called gene therapy.

Most gene therapy approaches so far have tried adding genes which in some way make the cell resist infection. Dr. Klatzmann suggests a different approach -- making cells which will quickly be killed if they are infected, by adding a gene which makes a toxin which will kill the cell, but which does so only under control of HIV regulatory sequences. His group did make such cells, and they completely stopped the spread of HIV in laboratory cultures. (This work was described in more detail in M. Caruso and D. Klatzmann, Selective Killing of CD4+ Cells Harboring a Human Immunodeficiency Virus- Inducible Suicide Gene Prevents Viral Spread in an Infected Cell Population, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, USA, January 1, 1992, volume 89, pages 182-186.)

* "Effect of Natural and Synthetic Lignins on HIV Infection and on Myeloperoxidase Activity," Takao Kunisada and others, Showa University, Tokyo, Nagoya city University, and Universit t Mainz, Germany [PuA6092]. This is a technical study relevant to previously-reported work with "a natural lignin from pine cone, and synthetic lignins from caffeic acid, ferulic acid, and p-coumaric acid," which were described as potent antiviral agents in laboratory tests in certain cells.

* "Antiviral Action of Polyadenylic-Polyuridylic Acid Against HIV in Cell Cultures; Synergistic Effect with AZT," Anne Laurent-Crawford and others, Institut Pasteur and Laboratoires Beaufour, Paris [PuA6095]. This drug, commonly called poly(A)poly(U), has been used in long-term cancer treatment with no toxicity observed, according to the abstract. Poly(A)poly(U) showed anti-HIV activity, and also made AZT work more effectively, in laboratory tests. The drug also stimulates natural killer cells and other components of the immune system. Like AZT, etc., it has no effect on chronically infected cells; it seems to work by preventing viral entry, so it would not help with cells that are already infected.

For More Information

For those who did not go to the conference and want to look further into some of the work mentioned here, the best way is to borrow the abstract volumes, or get copies of the abstracts of interest, from someone who went to the conference. Perhaps you can locate a set through a local AIDS organization or a specialized library. A few copies may still be available for purchase, but they cost $150 for the set -- for fifteen hundred pages of technical material reduced in size to tiny, hard-to-read type. (If photocopies are made, it is helpful if they can be enlarged, especially if they will then be sent by fax.)

This conference, for the first time, asked researchers to include their phone and fax numbers at the bottom of each abstract, so it is possible to contact them for more information. We find that fax works better than calling when there is a large time-zone change and/or a language barrier (since it is easier to find someone who can read a language than to have a speaker available whenever a call might come in).

920904
ATN15802

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1992. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .