Washington AIDS Conference, Part III (Part three of three parts)

This article concludes the discussion of HIV treatment papers presented at the III International Conference on AIDS,
Washington D.C., June 1-5 1987.

Note that the writeups below only summarize information presented at this particular conference. We have not had time to prepare a full background report on any of these treatments.

For the earlier articles in this series, see AIDS Treatment News June 19 and July 2. The reference numbers in
the text of this article refer to the volume of abstracts of Conference papers; to obtain the abstracts discussed here, see
below.

*** Foscarnet. Several papers reported successful treatment of CMV pneumonitis, CMV retinitis, and HIV itself in
persons with AIDS and ARC.

Foscarnet (chemical name trisodium phosphonoformate hexahydrate), an antiviral developed in Sweden by ASTRA
Pharmaceuticals, has shown activity against HIV, CMV, and all the herpes viruses. Side effects are usually small or moderate and they are reversible, although sometimes they are severe enough to require discontinuation of the drug. The main drawback of Foscarnet is that it needs to be administered continuously by intravenous infusion.

The results on CMV pneumonitis (THP 237) may be most important, because of the difficulty of treating this infection
by other means. This study by researchers at hospitals in England treated eight CMV pneumonitis patients with Foscarnet for between eight and 26 days. All of the patients improved, and seven left the hospital.

In the CMV retinitis study (session number Th 8.1, reported here from the abstract prepared before the Conference), Foscarnet was given to 10 patients, nine with AIDS and one with severe ARC. In five of the patients the retinitis resolved completely; in the others it improved or stabilized. But after the drug was stopped, retinitis returned in six of the eight surviving patients. In three of them, it responded to subsequent use of the drug; the abstract does not say whether the other patients failed to respond to Foscarnet the second time, or whether other treatments were used instead.

Two HIV studies (THP 13 and THP 238), one with eight patients and the other with 14, reported a decrease in the
ability to isolate HIV after Foscarnet treatment. One of these abstracts also reported clinical improvement; the other said
nothing about clinical status.

*** Glycosylation inhibitors. This paper (TP 23) reported a successful laboratory test of an approach to preventing the
virus from initially attaching to the cell, by blocking the expression of glycoproteins on the envelope of the virus. The glycosylation inhibitor used in this test was 2-deoxy-D- glucose. The authors, at universities in Philadelphia,
Wilmington DE, and Brussels, Belgium, suggested that glycosylation inhibitors might prove useful in treating AIDS.

*** GM CSF (Granulocyte-Macrophage Colony Stimulating Factor). This substance, produced by genetic engineering, increased the white blood count in a test of four different dosage levels on a total of 16 AIDS patients (MP 222). The counts returned to near their original levels two to 10 days after the drug was discontinued. The authors suggested that GM CSF might be useful either alone, or in combination with antivirals.

Note: According to a report published after the Conference, GM CSF might cause the AIDS virus to replicate.
Anyone considering using the treatment should investigate this serious risk. See "Cytokines Alter AIDS Virus Production", Science June 26 1987, page 1627.

*** HPA-23. Two studies, one in Paris and one in New York, had little remarkable to report (WP 216 and WP 218).
Both found moderate side effects, especially decreases in the number of platelets, but these effects were reversible when the treatment was discontinued. The French study found some success in HIV inhibition, but did not state whether there had been any clinical improvement. The New York study only reported on side effects in the abstract reviewed here.

*** Imreg 1. Two poster sessions by the same authors (MP 218 and THP 241) reported on this substance, which is extracted from normal human white blood cells. One of the reports summarized the results of 50 patients with AIDS or ARC who have been treated repeatedly with Imreg 1 for over several months.

T-helper cells increased or did not fall in 23 of 48 patients followed for at least three months. Delayed hypersensitivity returned in 60 percent of the patients. Some patients showed clinical improvement such as weight gain, but the abstract did not report how many benefitted. The best results were found in persons starting with T-helper counts of 100 or more. A new study will enroll 150 patients with ARC or recent-onset KS.

*** Isoprinosine. This immune modulator is widely used in dozens of countries, but has long been out of fashion in the
U.S., for reasons unclear. Persons with AIDS and ARC in this country have for several years obtained supplies from Mexico, often for use in combination with ribavirin.

One poster session at the Conference (MP 132) reported a study of Isoprinosine by researchers at Mount Sinai School of Medicine in New York. The study consisted of complex laboratory tests of blood from ARC and AIDS patients who were using Isoprinosine. The highly technical abstract concluded that Isoprinosine "initiated a cascade of cellular interactions leading to restoration of cell-mediated immune responses. These interferences with the defective helper/suppressor regulatory pathways may have important therapeutic implications."

*** Milk from hyperimmune cows. This treatment for chronic intestinal cryptosporidiosis was tried on three
patients with AIDS, at the St. Luke's-Roosevelt Hospital Center in New York (THP 148). All three improved, and in the two who were tested, the organism disappeared from the stools.

The treatment consisted of proteins extracted from the milk of cows vaccinated with a preparation of human intestinal
bacteria. The milk was specially pasteurized to avoid destroying the antibodies.

The researcher concluded that "While preliminary, the results strongly suggest that a large molecular weight fraction
in cow's milk effectively suppresses cryptosporidiosis in patients with AIDS." This study is important because cryptosporidiosis, which causes chronic diarrhea, has resisted treatment with available drugs.

*** Naltrexone. A poster session at the Conference (WP 227) released more information from the same research project described in our article, "Naltrexone for AIDS/ARC", AIDS Treatment News October 24, 1986. Naltrexone, a prescription drug normally used to keep opiate addicts off drugs by blocking opiate receptors so that narcotics will have no effect, is taken in very small doses before bedtime by persons with AIDS or ARC, to stimulate the pituitary to produce more endorphins, the body's "natural opiates". The result seems to enhance the immune system; in fact, endorphins may be the mechanism by which exercise or good morale can be helpful.

The abstract presented at the Conference reported a double-blind placebo-controlled study with 39 patients, 38 with
CDC defined AIDS and one with ARC. Those getting the naltrexone showed a significant drop in a form of alpha
interferon which is usually too high in these patients. After three months, the placebo study was ended and all patients
received the naltrexone.

Of the 39 patients on naltrexone, 23 showed a large decline in alpha interferon over a one-year period; 16 failed
to respond. There were far more opportunistic infections and deaths in the non-responder group. As of December 1986, 81 percent of the non-responders had died, compared to 17 percent of the responders.

No side effects were seen.

These results support the earlier impression that naltrexone appears to be helpful to some people, and appears to
have no drawbacks.

*** Phosphorothioate analogs of oligodeoxynucleotides. This laboratory study by researchers at the U.S. National
Cancer Institute and Food and Drug Administration tested what may become a new class of antiviral agents (T 4.4). Different chemicals of this class were effective in different degrees against HIV in laboratory tests. At least one worked
synergistically with dideoxyadenosine (DDA), an experimental antiviral related to AZT or DDC.

*** Rifabutin (ansamycin). A study found that this drug, used to treat the opportunistic infection MAI but which also
can inhibit HIV in larger doses, does cross the blood-brain barrier, thereby fulfilling one requirement of an HIV
treatment. The drug had been given orally for several weeks. The abstract (THP 228) does not state whether any clinical benefits or side effects were found.

A related study (THP 233) -- also by researchers at SUNY in Stony Brook NY, Long Island Jewish Medical Center in New Hyde Park NY, and the U.S. Centers for Disease Control in Atlanta GA -- is giving increasing doses of rifabutin to
patients until either antiviral or toxic effects are found. The published abstract, written before the Conference, reported
neither effect at 600 mg. New information may have become available later. Incidentally, the researchers chose rifabutin because it inhibits HIV in the laboratory, has low toxicity when used to treat MAI, crosses the blood-brain barrier, and is given orally.

*** Tumor necrosis factor. This abstract (T 4.5) reported that tumor necrosis factor and alpha interferon worked together to protect cells against HIV in the laboratory.

*** Vaccines. Vaccine development has become a major area of AIDS research; we cannot summarize it here. Note that some of the potential vaccines being developed for AIDS are also treatments; they might work after persons have been infected with the AIDS virus, or even after they have become ill.


For More Information

For a copy of Conference abstracts on treatments, including all the abstracts referenced in this series of
articles, send two dollars to: John S. James, P.O. Box 411256, San Francisco, CA 94141.