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Issue #221: March 19, 1999
fastfax is available by fax in the 215 and 610 area codes at no cost, or by mail anywhere for $20.00 per year, by calling 215-545-6868, and by E-mail by contacting and type the message SUBSCRIBE in the message section. Sources for some articles in this issue include Associated Press, The Lancet, Proceedings of the National Academy of Sciences, Reuters, Science, Seattle Times.
In This Issue:
Discovery may help AIDS vaccine development
HIV drugs beneficial despite viral rebound
Washington State board adopts policy on names
Protein in tears, saliva may combat HIV
Judge throws out hemophilia judgement
In France, victims rage at verdict in blood trial
Marlton Court applications accepted April 1st
Scientists have announced that they had figured out how the immune system "remembers" enemies it has encountered in the past, a discovery that could lead to better vaccines and perhaps treatment for HIV.
A report in the journal Science shows that so-called memory T-cells are extremely slow learners -- and it suggests that some AIDS researchers have been on the wrong path in trying to design a vaccine.
Immune cells known as T-cells are very important in defending against invaders such as viruses or cells that are starting to become cancerous.
Scientists knew that one particular type of T-cells, known as CD8 cells, could either become vicious attackers that immediately kill invaders, or could become "memory" cells that help to quickly flag such invaders if they ever show up again.
But just how this happened was murky.
Joseph Opferman and colleagues at the University of Chicago found that the process by which memory cells are made is excruciatingly slow. They found several generations of the cells must be exposed to a troublemaker before some of them can become memory T-cells specific for it.
"This finding suggests that the typical approach to vaccines for treatment of cancer or AIDS is not often likely to produce the desired result," Philip Ashton-Rickardt, one of the researchers, said in a statement.
"But it also shows us how we can get around the problem."
Scientists have long understood how another kind of immune cell known as a B-cell works and forms its own kind of memory cells.
But T-cells are key to making some vaccines work and are central to fighting off HIV infection which causes AIDS because the virus specifically attacks T-cells.
When an invader enters the body, or when a cell starts to go haywire and become cancerous, T-cells rush to the scene and multiply. Some become cytotoxic T-lymphocytes (CTLs), which literally dissolve other cells.
After a while most of the surplus T-cells die.
The University of Chicago team found that a few remain, with a memory imprint of whatever troublemaker has been tackled. The next time, their response should be quicker.
But for any number of these cells to form, the battle has to have gone on for some time -- for at least five cycles of cell division.
That could be why no AIDS vaccine has worked properly, Ashton-Rickardt said. Researchers have complained that their vaccines do not generate many CTLs.
"No vaccine trial to date has been able to produce significant numbers of memory T lymphocytes, which are important in killing HIV-infected or cancerous cells. Now we know why, and we have a pretty good idea of how to change that," he said.
Working with mice, they cultured memory T-cells in dishes and kept exposing them to antigen - the marker they use to identify enemies -- for up to five days.
When injected back into mice, the memory cells kept their memories for as long as 10 days.
"They remembered and went after their targets as soon as they were exposed to them again. Although mice with normal immune systems take two or three days to mount an immune response, these memory T-cells responded immediately," Ashton-Rickardt said.
Such a method might be used to make better vaccines against a range of diseases, including HIV and cancer.
HIV drugs beneficial despite viral rebound
Patients on anti-HIV drug cocktail therapies continue to do well, even when they experience "viral rebound," where levels of the virus rise again to detectable levels in their blood, according to a report in the March 13th issue of the British journal The Lancet.
"Clinically speaking, these patients remain in reasonably good health despite an increase in (their) viral load," explained Dr. Rainer Weber of the University of Zurich in Switzerland.
Highly active antiretroviral therapies (HAART) are drug 'cocktails' involving the use of one protease inhibitor combined with two other antiretroviral drugs. In some (but not all) patients with HIV, these therapies reduce blood levels of the virus to near undetectable levels.
However, in recent years, experts have noticed an increasing incidence of viral rebound in these patients -- a resurgence of HIV from previously undetectable levels. This phenomenon suggests that HIV is mutating against the multi-pronged arsenal of HAART therapy.
In their 3-year study, the Swiss researchers tracked the health and blood HIV levels of 2,674 outpatients. The subjects began HAART between 1995 and 1998. For some subjects, HAART marked their first experience with combination therapies. Others had switched to HAART from other treatment regimens.
After 1 year, viral load fell to undetectable levels in 90.7% of first-time patients and in 78.7% of previously treated patients.
However, after 2 years, the authors documented viral rebound in 20% of the first-time patients and in up to 40% of previously treated subjects.
At 2.5 years of follow-up, progression to AIDS or death had occurred in 6.6% of those with sustained undetectable viral load compared with 9% of those who rebounded -- a statistically insignificant difference.
According to Weber, this means that "even in patients affected by a viral rebound, the disease has not developed any more than in patients whose viral load remained undetectable."
Chief investigator of the study, Dr. Bruno Ledergerber, comments in a statement, "Our study (also) shows that it is better to start treatment with a potent combination of at least three drugs, rather than administering different substances sequentially, one after the other."
As usual, some patients did not have reductions of viral load to undetectable levels, and the investigators report that one in five of these patients either died or developed AIDS within the study period. Still, they note that this death/AIDS rate remains much lower than that of patients treated in the years before drug cocktails.
"This finding is explained by an important rise in CD4 count, which is maintained despite detectable virus," the authors explain. High levels of CD4 immune cells help maintain a functioning immune system, protecting patients from potentially lethal opportunistic infections.
Washington State board adopts policy on names
by Warren King
Seattle Times
A heated, year-and-a-half controversy over privacy rights and how to report new cases of AIDS infection has moved significantly closer to resolution as state health officials lean toward a system to encode patients' names after a brief period.
The state Board of Health voted unanimously yesterday to draft a rule requiring that initial reports to local health departments include names of those infected with HIV. The names would be encoded after 90 days for submission to the state. Then the local health department would delete the names from their records.
A board vote on the rule probably will be taken by midsummer, officials said. Additional hearings will be required on the issue, one of the longest, most emotional health controversies in recent state history.
"I think they took an important step forward in building trust with the affected communities," said Steve Johnson, policy director for the Northwest AIDS Foundation. "It's a recognition of the partnership between public health (officials) and the communities."
The move was a reversal of the board's controversial proposal last October that names be used for all reports, as they are for 54 other infectious diseases.
Some members of the Governor's Advisory Council on HIV-AIDS and HIV-patient advocacy groups, which had urged using only codes, were infuriated by the abrupt action.
Yesterday's move follows a January recommendation by the King County Board of Health that reports with names be converted to code after 90 days. The county board forged a compromise recommendation on the advice of an advisory "common-ground committee" that involved health officials and community members.
Cases of full-blown AIDS have always been reported. Now health officials and advocacy groups alike agree that HIV infections also should be reported because new drug therapies enable patients to live longer.
The reports, including demographic data, would enable officials to better predict the epidemic's direction, get early treatment to those infected and improve AIDS-prevention efforts. Most states already require HIV reports, most with names.
Many community members still oppose the use of names, even to local health departments. Members of a group called Resist the List testified before the board yesterday that the proposed system would cause fear and reluctance by many to be tested for HIV.
"Having grown up in Walla Walla, I can tell you the last place an HIV-positive person would want to have his or her name on a list is a local health department in a small town. You might as well put it on the Internet," said Bill Lake, leader of Resist the List.
Johnson, of the Northwest AIDS Foundation, said the compromise is still a significant victory. Health officials statewide initially were insistent on a names-only system.
"No organization has put more time or energy . . . into getting the state to use only (codes)," he said. "While we didn't get all we want, we're proud of the effort to get the additional protection of having the names destroyed after 90 days."
A major provision of the proposed rule would be to ensure the continued availability of anonymous HIV testing and that all patients are informed of the option. However, once an infected person sought treatment and a confirmatory test was given, the results would have to be reported.
Other details the board specified for the proposed rule include:
-- A provision for an evaluation of the system after it has been in effect for a year. The national Centers for Disease Control and Prevention has several requirements for reporting systems, including that at least 85 percent of those tested actually be reported and that at least two-thirds of new cases be reported within six months of the tests.
-- Once the rule takes effect, a way to allow phased-in reporting of HIV cases diagnosed before the effective date. Health officials estimate more than 10,000 state residents now are infected with HIV. About 750 new infections occur each year.
-- Laboratories also must report HIV cases. The rule should specify an efficient, central clearinghouse for distribution of the reports to appropriate county health departments. Names could not be recorded at the state level.
Protein in tears, saliva may combat HIV
Researchers have found that tears, saliva and pregnant women's urine contain proteins that are powerful killers of HIV.
In a study published in the Proceedings of the National Academy of Sciences, scientists found that a protein called lysozyme was able to kill HIV quickly in test-tube experiments.
Sylvia Lee-Huang of New York University, lead researcher in the study, said the protein could become an important drug against HIV because it is a natural compound that the body routinely makes in tears and saliva.
"It ought to be more tolerated and have fewer side effects than other HIV drugs," said Lee-Huang. "It possibly could be used in combination with other drugs."
It's not known how lysozyme kills HIV, but Lee-Huang speculated that it could work by breaking down the outer membrane of the virus.
The team also found that the urine of pregnant women contains another type of protein, called ribonucleases, that destroys the genetic material in HIV.
Nava Sarver, an AIDS researcher at the National Institute of Allergy and Infectious Diseases, said the study was interesting but needs to be confirmed by other laboratories.
"A lot of work needs to be done to simulate the (laboratory) findings in a more relevant situation," said Sarver. Her agency, NIAID, is part of the National Institutes of Health.
The search for the anti-HIV protein was prompted, said Lee-Huang, when researchers realized the babies of women infected with HIV were somewhat protected from the virus.
Researchers earlier suspected that human chorionic gonadotropin, or HCG, a hormone produced during pregnancy, was responsible for protecting against HIV and other viruses.
Lee-Huang said she and her group purified HCG and found it had no effect on HIV. The researchers then spent two years isolating other proteins in urine and testing them against HIV. Eventually they found lysozyme and ribonucleases.
The researcher speculated that pregnancy prompts a woman's body to make more virus-killing proteins to protect the developing baby from viruses and bacteria. That suggests "Mother Nature knows best how to protect the earliest stages of life," Lee-Huang said.
The proteins also were found in mother's milk, white blood cells and chicken egg whites. The presence of lysozyme in saliva may be a factor in why HIV is not transmitted by casual kissing, said Lee-Huang.
The team is trying to determine exactly how lysozyme attacks HIV. That is a critical step in developing a new HIV drug based on the protein, she said.
Judge throws out hemophilia judgement
A judge has thrown out a jury verdict awarding $35.3 million to a couple who blamed the AIDS death of their hemophiliac son on tainted blood-clotting medicine.
Relatives of other hemophiliacs who died after receiving allegedly tainted medicine embraced and wept as the jury's verdict was read. But they sat stone-faced a short time later when Orleans Parish Civil District Court Judge Max Tobias threw out the ruling, saying the family of Kenneth Dixon had waited too long to sue.
Tom Mull, the lawyer for Leo and Shirley Dixon of Lafayette, said he will appeal Tobias' ruling. "I am extremely pleased by the fact that the jury decided what we have known all along, that the defendants are guilty of gross negligence and wanton disregard for the safety of their consumers and the American public," Mull said. "We asked for justice and we got it from the jury."
The Dixons claimed that Kenneth Dixon died as a result of receiving tainted clotting medicine made by Miles Inc. - now Bayer Corp. - and Alpha Therapeutic Corp.
The jury found the companies knew or should have known the medicine was tainted with HIV, the virus that causes AIDS, and fraudulently misrepresented its safety.
Dixon sued the drug companies in 1993. When he died in 1995 at 27, his parents took over as plaintiffs and raised claims for their son's wrongful death in 1997.
But the judge said the family learned in 1985 that he was infected and should have sued by late 1990.
Tobias waited until jurors had left the courthouse to announce his ruling, which he had written earlier but sealed until the jurors finished deliberations. He said he had "gone back and forth" on the statute of limitations issue but that he believed time had run out on all the Dixon's claims.
The defendants, who are facing trial in several similar cases in New Orleans, may appeal the jury's findings.
The drug companies maintain they did nothing improper and the medicine was tainted before anyone knew AIDS existed. The jury did not find two other defendants, Baxter Healthcare Corp. and Armour Pharmaceutical Co., liable.
In France, victims rage at verdict in blood trial
Victims and their families reacted with cynicism, outrage but little surprise earlier this month when a special court in Paris absolved two former ministers and imposed no punishment on a third for their role in the contamination of French blood banks with HIV in the mid-1980s.
The former prime minister Laurent Fabius was cleared by the semi-judicial, semi-political court, which accepted his claim that he had accelerated, not delayed, the systematic checking of blood stocks for HIV. His former social affairs minister, Georgina Dufoix, was found not guilty of manslaughter and bodily harm but reprimanded for incompetence.
The third defendant, the former junior health minister and Mayor of Rennes, Edmond Herie, was found guilty of failing to prevent contaminated blood-stock samples from being used in two cases. But the Cour de Justice de la Republique, a panel of three judges and twelve politicians hearing its first case, decided no punishment should be imposed.
"Why not give them the Legion d'honneur," shouted Patrice Gaudin, father of two hemophiliac children who died of AIDS after being given HIV-infected blood products. Joelle Bouchet, whose son caught AIDS in similar circumstances, shouted: "Murderous state. The justice system is its accomplice ... You have blood on your hands, Mr. Herve."
The three former ministers were accused of having delayed the systematic checking of blood stocks for commercial reasons from March or April until August of 1985, exposing 300 to 600 people to the AIDS virus. About half have since died. The two junior ministers were charged with allowing the state blood service to use old blood products for hemophiliacs rather than incur the cost of destroying them.
The main case against the ministers rested on the claim that the Fabius government intervened on behalf of Diagnostics Pasteur, a French company struggling to complete its own system for testing blood for HIV. As a result, it was said, the use of a rival American test was blocked and delayed.
All three ministers denied this version of events, as did the man who at the time was head of Diagnostics Pasteur, Jean Weber, despite documentation that he led a successful protectionist campaign through his contacts in the Fabius government.
Victims and their families were outraged that the court made no attempt to cross-examine the accused or witnesses, despite apparent discrepancies in their statements to the court.
Jean-Frangois Mattei, a liberal member of the French parliament, described the trial as a "triple failure - politically, judicially and morally".
The affair is not over. This week an investigative judge is expected to make a much-delayed decision on whether to proceed with criminal cases for "poisoning" against a dozen senior officials also involved in the affair, including Jean-Pierre Allain, then deputy head of the French blood service, who has since become Professor of Hematology at Cambridge University.
Marlton Court applications accepted April 1st
Marlton Court, We The People's new apartment building in the Parkside section of West Philadelphia, comprised of 25 one-bedroom units, will begin accepting applications at the Life Center, 425 South Broad Street, at 10:00 a.m. on April 1st.
Rob Capone, executive director of We The People, said that applications will be accepted on a first-come, first-served basis. All applicants must come to the Life Center to apply, and have with them proof of income and proof of their HIV status. The apartments, part of WTP's low-income housing program, offer rents of $200 per month plus utilities to individuals making $19,000 per year or less who are HIV-positive.
No medical status standard is applied in considering applications beyond HIV infection.
Individuals who seek to apply without proof of income and proof of HIV status will not be placed on the application list until a full application is completed, Capone said.
For more information, call 215-545-6868.
Marlton Court is expected to open its doors on May 1st. An open house will be announced sometime in April.
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