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Issue #250: October 8, 1999
FASTFAX is available by fax in the 215 and 610 area codes at no cost, by mail anywhere for 20.00 per year, by calling 215-545-6868, and on the fastfax index page. Information in fastfax is drawn mostly from secondary sources; people living with HIV/AIDS should share information of interest to them with their primary care provider before making treatment choices. For more information on HIV medications and treatments, contact Kiyoshi Kuromiya of the Critical Path AIDS Project, 215-545-2212 or by email to The presence of the name or image of any individual in fastfax should not be construed as an indication of their HIV status or sexual preference unless specifically stated. Questions or comments should be directed to Editor, fastfax, 425 S. Broad St., Phila., PA 19147-1126 or by email to
In This Issue:
New drugs may block HIV's entry into cells
AIDS deaths decline 70% since 1995
600 protest US AIDS drug policy
Good microbicides five years away: report
FDA panel says overseas HIV studies acceptable
FDA says Immunex's AIDS claims are "misleading"
Boy with AIDS loses karate court battle
A group of scientists who have spent the past few years studying how the AIDS-causing virus infects cells said they have found an experimental class of drugs they believe can block the virus from entering cells, a finding that may some day lead to the first drugs that can actually prevent an infection from occurring in the first place.
The scientists, at Massachusetts Institute of Technology's Whitehead Institute for Biomedical Research, said they are making the discovery available, on a nonexclusive licensing basis, to researchers at any pharmaceutical company interested in trying to turn the research into usable medicines. If the drug makers can use the new research to produce new virus-blockers, the MIT scientists will have identified an important addition to the growing number of drugs being widely used in combination to fight off HIV, the virus that causes AIDS.
The researchers, led by Peter S. Kim, are reporting that they have produced a small chemical that, in laboratory tests, can neutralize the action of a hook-like protein that sits on the outer coat of HIV and is used by the virus to enter human cells. Drugs based on the new molecule would represent a novel class of medicines to inhibit HIV.
Most existing anti-HIV drugs work differently, by blocking the virus from reproducing itself once it is already inside cells. An innovative anti-HIV drug would be especially valuable because HIV has developed numerous strains that can resist the action of the existing drugs and threaten to reduce the effectiveness of the current drug "cocktails" that have revolutionized AIDS treatment since being introduced in early 1996.
The new finding may even help drug makers produce the first-ever pill that could be used to prevent someone exposed to HIV from becoming infected. Such a pill would have to be taken continuously to provide long-term protection but might conceivably be used as a "morning-after" pill by someone exposed to HIV. That, however, would be some time in the future since no major drug maker was even aware of the new research until its publication Friday in the scientific journal, Cell.
"No drug currently exists, and no company has yet asked to license" the discovery, said Lita Nelsen, director of technology licensing at MIT, who said Whitehead has sought a patent for the new research. "We do expect interest from those drug companies who want to use the new technology to find a new class of drugs," she said.
The new finding results from several years of investigation by Dr. Kim and his colleagues, who have been analyzing the chemical structure of the protein called gp41. HIV attaches itself to a target cell with another nearby protein called gp120. After that happens, however, the gp41 protein emerges from inside the virus's outer membrane and, in a split-second action, hooks itself onto the cell, thereby fusing the virus and the cell. Once inside the cell, the virus replicates and sends out its offspring to colonize other cells. Each new virus then uses gp41 as the critical last step to gaining entry to the host cells. Two years ago, Dr. Kim's lab made a critical breakthrough when it produced a computerized, three-dimensional image of the protein. Before this, researchers had been unable to isolate the protein or its structure because it changes shape so swiftly as it emerges from hiding, spears a cell, and draws the virus and cell together. The Kim lab, in essence, was able to produce a "freeze-framed" image of gp41.
"And when we did that, we saw that during this process, a pocket is briefly formed that gp41 uses to bind to cells," said Dr. Kim, whose research lab is funded by the Howard Hughes Medical Institute. "What we've done now is show that a small molecule, one small enough to be used as an oral drug, can bind to this pocket and block the virus from entering the cell."
In experiments being reported in the Cell paper, the Whitehead researchers mixed the experimental chemical in a test tube containing HIV and target cells. Instead of infecting the cells, the HIV was kept locked outside, the researchers report. As a result, Dr. Kim said they have dubbed the new type of drugs gp41 "pocket-blockers."
At present, only Trimeris Inc., a young company in Durham, N.C., has produced a drug with a somewhat similar action. That drug also blocks gp41 but does so by binding to a different part of the protein. Trimeris's drug, called T-20, is already in human trials. Doctors are anxiously awaiting T-20 to help treat people who have developed resistance to existing drugs, but T-20's usefulness may be limited because it must be injected twice a day and is expected to be very expensive. (Wall Street Journal)
Rates for AIDS deaths, homicide and teen births all dropped again in 1998, but the U.S. infant mortality rate leveled off after years of decline, according to new preliminary vital statistics released by US Health and Human Services (HHS) Secretary Donna E. Shalala.
The data were published in a new report, "Births and Deaths: Preliminary Data for 1998," prepared by the National Center for Health Statistics (NCHS), a part of the Centers for Disease Control and Prevention (CDC).
According to the report, the age-adjusted death rate from HIV infection in the U.S. declined an estimated 21 percent to a rate of 4.6 deaths per 100,000 in 1998, the lowest rate since 1987, after a 48 percent decline from 1996 to 1997. HIV mortality has declined more than 70 percent since 1995. The disease was the eighth leading cause of death in 1996, dropped out of the top 10 leading causes of death last year, and no longer ranks among the top 15 leading causes of death today.
However, for the 25-44 year age group the disease still ranks fifth among leading causes of death.
The trends in AIDS death rates are uneven across racial and ethnic groups. HIV remains the leading cause of death among African American men ages 25-44, and the third leading cause of death among African American women in the same age group.
"Today's report confirms the many positive trends in America today: longer life expectancy, fewer teen births, lower rates of violent crime and homicides, and a significant decline in deaths from HIV and AIDS," Secretary Shalala said. "But it's important that we continue to work together to broaden our progress in disease prevention. This is particularly true in communities of color, which still suffer disproportionately from infant mortality and AIDS."
Other key findings in the report include the following:
-- The preliminary age-adjusted homicide rate fell an estimated 14 percent in 1998, the fifth straight year of decline. However, homicide remained the leading cause of death for black males 15-24 years of age.
-- Life expectancy reached a record high of 76.7 years for everyone born in 1998.
-- Timely prenatal care also reached record levels in 1998 as an estimated 82.8 percent of women received care in their first trimester of pregnancy.
-- The teen birth rate also fell 2 percent in 1998, continuing a seven-year trend. The birth rates for teenagers 15-17 years dropped 5 percent for 1998 to a record low of 30.4 per 1,000. From 1991-98, birth rates for non-Hispanic white and black teens 15-19 years dropped steeply: 19 percent and 26 percent, respectively.
"Reducing teen pregnancy and teen birth rates has been a national goal, so this trend is very encouraging," said CDC Director Dr. Jeffrey Koplan. "It is the result of a lot of very hard work with our partners at the federal, state, and grassroots level. But we can't afford to stop our efforts now -- too many teenagers are still jeopardizing their futures."
Other findings in this report were less encouraging:
-- No change in the preliminary infant mortality rate. In 1998, the overall infant mortality rate was 7.2 infant deaths per 1,000 live births, the same as the record low reported in 1997. It is the first time there has been no improvement in this measure in nearly four decades. In addition, disparities remain between different race groups, as the rate for black infants is still twice the rate for white infants.
-- An increase in nonmarital childbearing. The preliminary number of births to unmarried women in 1998 was 3 percent higher than in 1997, due mostly to the increase in the number of unmarried women of childbearing age. The birth rate for unmarried women was 44.3 per 1,000, one percent higher than in 1997, but below the peak level reported for 1994.
-- An increase in the percent of low birth weight babies (less than 2, 500 grams). Low birth weight babies accounted for 7.6 percent of all births, compared to 7.5 percent in 1997. This increase was confined to non-Hispanic white women. The percentage of low birth weight babies remained unchanged for births to African American and Hispanic women, although the proportion of low birth weight babies for African American women is still almost twice that of white and Hispanic women.
-- An increase in the percent of cesarean deliveries, from 20.8 percent of all deliveries in 1997 to 21.2 percent in 1998. The primary cesarean rate (the proportion of first cesarean deliveries among women with no previous cesareans) increased by 2 percent in 1998, the first increase observed since these data were first collected from birth certificates in 1989.
The report features preliminary data collected through the National Vital Statistics System from more than 85 percent of death and 99 percent of birth records. The information on causes of death is recorded on death certificates by physicians, medical examiners, and coroners, and is then reported to the states. "Births and Deaths: Preliminary Data for 1998," is available at the NCHS Web site at http://www.cdc.gov/nchswww.
Fourteen AIDS protesters were arrested in Washington, D.C., on October 6th for disrupting traffic as they called for more affordable AIDS treatments in developing countries
In all, about 600 protesters marched from Farragut Square to the office of U.S. Trade Representative Charlene Barshefsky. While officials in some nations say they hope to offer increased access to AIDS drugs, U.S. pharmaceutical companies consider some laws in these nations, which permit inexpensive imports or locally produced generic treatments, as a violation of their patents.
The protesters chanted "Pills cost pennies. Greed costs lives." The protest was organized by ACT UP Philadelphia and other groups.
Health officials in countries such as South Africa say they want to provide more access to AIDS treatments, but have been prevented from doing so by companies concerned about maximizing their profits. Thomas Tripp, a spokesman for Barshefsky's office, said there are compromises that can be made to both protect "intellectual property and support sound public health policy."
The protesters accused Barshefsky of supporting U.S. pharmaceutical companies by using the threat of economic sanctions to prevent developing countries from producing generic drugs vital in the fight against AIDS.
Demonstrators contended the U.S. government supports large pharmaceutical companies who want to maintain high prices for drugs. The mix of drugs necessary for AIDS patients is too expensive for most residents of developing countries, said Julie Davids, a spokeswoman with ACT UP.
The organization has been demonstrating for months against U.S. policies toward South Africa after that country passed a law giving itself unspecified power to import AIDS drugs from counties where they are sold more cheaply or to license production within South Africa.
The United States was pressuring South Africa to amend the 1997 law but backed down last month after South Africa signed an agreement not to implement it in a way that would violate patent rights or other world trade rules.
Vice President Al Gore had urged trade officials to work out some kind of deal with South Africa after ACT UP protesters started dogging him at public appearances, including political events promoting his 2000 presidential bid.
Now, activists say, the trade office is still restricting other developing countries from getting affordable lifesaving medicines.
"Saving lives in Thailand, Brazil and India is just as vital as saving lives in South Africa," Chris Kimmenez of ACT UP said in a statement before the protest. (Reuters, AP, Washington Post)
Although several vaginal microbicides to prevent HIV transmission are in development, it will be another 3 to 5 years before any of these products can be approved for use in the US, researchers said at a New York conference.
Speaking at the meeting at Rockefeller University, Dr. Polly Harrison of the Alliance for Microbicide Development said that development of these products has been slowed by a lack of resources because large pharmaceutical companies have shown little interest.
Dr. Johannes van Dam of the Population Council said that the prevalence of heterosexual transmission worldwide creates a "compelling need for prevention methods that are more under the direct control of women." He noted that "the same factors that affect women in developing countries are also at play in the United States," where heterosexual transmission is increasing.
These factors include "violence, coercion, and economic dependency in relationships," Dr. Geeta Rao Gupta, of the International Center for Research on Women, said. Condom use, she added, is "universally difficult to achieve, especially in stable relationships."
Dr. Zeda Rosenberg of the HIV Prevention Trials Network at Family Health International, and other speakers noted that spermicidal products containing nonoxynol-9, which inactivate HIV-1 in vitro, appear likely to create conditions that promote transmission, such as irritation and inflammation. Speakers reported that products using otoxynol-9, which is less toxic to vaginal tissue, are being investigated.
Other topical antiviral agents discussed at the meeting included carrageenans, which inhibit viral entry and cell fusion, and have been effective in simian models. PRO 2000, which has been shown in animal studies to be nonmutagenic and non-toxic to vaginal, penile and oral tissue, is highly protective, according to other presenters.
Dr. Rene Crombie of the Weill Medical College of Cornell University described ongoing work there with thrombospondin-1, a compound found in saliva that appears to inhibit HIV-1 and a number of bacteria in vitro.
At the New York Blood Center, Dr. Robert Neurath and his colleagues are investigating cellulose acetate phthalate, commonly used in enteric coatings for tablets, which has also shown inhibitory effectiveness in vitro against HIV and herpes simplex 1 and 2. (Reuters)
A Food and Drug Administration (FDA) advisory panel, wrestling with how drug studies aimed at preventing mother-to-child transmission of HIV should be conducted, has said that since it has become increasingly clear they will not be carried out in the US, overseas trials could be accepted with some conditions.
The Antiviral Drugs Advisory Committee made suggestions on how those foreign trials could be designed to pass muster at the FDA. For instance, the panel said, controlled trials would be preferable. In a traditional controlled trial, some study participants receive the drugs being tested, and some receive (an inactive) placebo. But placebo controls are no longer necessary, said committee members. And, if there was no way to use a control, in some cases epidemiological data could be collected from other kinds of studies, panelists suggested.
"We need to put into place control (groups of patients) that are ethically acceptable and regionally specific," said panel chairman Dr. Scott Hammer of Columbia Presbyterian Medical Center, who said that as long as studies were conducted with accepted methodologies and competent investigators, the results should be acceptable.
"If a trial's well done, then the results should be believable," agreed Dr. Courtney Fletcher of the University of Minnesota, a consultant to the panel. But Fletcher added that with study populations that would differ from the US in many ways, it might be difficult to apply the results to American patients and clinical practice. "That's where we have the real challenge ahead of us," he said.
Hammer and other panel members disagreed somewhat. "I think inferences will be made to incorporate the data into practice in the US," said Hammer.
US studies are not likely to occur because both the incidence of HIV infection in newborns and pediatric AIDS cases have declined significantly, said Debra Birnkrant, deputy director of the FDA's antiviral drugs division. The Centers for Disease Control and Prevention, collecting data from 32 states, has observed a major decrease in reported cases.
Birnkrant also noted the broad acceptance of a three-part regimen of Glaxo-Wellcome's zidovudine (AZT) -- the only drug with FDA-approved labeling for preventing maternal transmission. Given this, and the small numbers of patients available for study, most transmission trials would have to be done outside America, said Birnkrant.
There is a broad pool of alternatives to zidovudine; 14 antiretrovirals are approved for marketing in the US. New data from international studies shows that a short-course, two-dose nevirapine regimen also prevents HIV infection during pregnancy or delivery.
"There is clearly a need for more data and guidance," on the use of other approved antiretrovirals to prevent transmission, said Heidi Jolson, director of the FDA's division of antiviral drugs.
There is less information available on whether solely giving infants antiretroviral therapy just after birth prevents infection or progression to AIDS. But there could be soon. The AIDS Clinical Trial Groups are currently developing a study that would test nevirapine as an infant prophylaxis, which could start enrolling next year, said Lynne Mofenson, associate branch chief for clinical research at the National Institutes of Health. She also noted there is an international study of postpartum prophylaxis, and there are at least six trials testing different regimens of antiretrovirals underway in the US. (Reuters)
Immunex Corp. made "false and misleading" claims last May that its cancer drug Leukine was shown in a clinical trial to help fight HIV, the U.S. Food and Drug Administration has charged.
The FDA, in a warning letter released Oct. 5th, said Seattle-based Immunex made the statements in a press release issued May 3rd.
The press release said a clinical trial showed Leukine helped keep levels of HIV suppressed and
allowed patients to take antiviral drug cocktails longer without developing resistance.
The press release "contains representations and suggestions that are false and misleading," wrote Steven Masiello, a top official in the agency's Center for Biologics Evaluation and Research.
An Immunex spokeswoman responded by saying that the company had stopped distributing the press release and removed it from its Web site.
"We consider the matter closed at this time," spokeswoman Cathy Keck Anderson said.
Keck Anderson said the press release "describes data presented at a medical meeting. It describes factual data." She declined to discuss whether Immunex agreed with the FDA's charges.
Already approved to treat certain cancers, Leukine generated second-quarter net sales of $16.6 million, making it Seattle-based biotechnology company's second-best-selling product behind arthritis drug Enbrel.
The FDA objected to Immunex's statements in the May press release that Leukine, known generically as sargramostim, helped keep HIV suppressed in a Phase III clinical trial.
Investigators reached conclusions based on unblinded data, Masiello wrote in the letter, which was sent Aug. 23 and released to reporters on Oct. 5th. Blinding prevents investigators or subjects from knowing the hypotheses or conditions being tested so results can be analyzed objectively.
"Consequently, any representations or claims regarding an effect upon change in antiviral therapy and incidence of all infections are not valid," Masiello wrote. (Reuters)
A Virginia boy with AIDS who wanted to take "hard-style" karate lessons with his friends has lost his U.S. Supreme Court appeal.
The justices, without comment, left intact rulings that said Michael Montalvo's participation in a rough-and-tumble karate school would pose too much of a threat to the health and safety of other students.
Michael's father, Luciano, had sued the karate school, saying its refusal to let his son participate in group classes violated a federal anti-discrimination law, the Americans with Disabilities Act.
Michael was 12 when in 1997 he applied to take karate lessons at U.S.A. Bushidokan, a karate school in Colonial Heights, Va., run by James Radcliffe II.
After learning that Michael had Acquired Immunodeficiency Syndrome, Radcliffe refused to let him participate in group classes.
His offer to give the boy private lessons was rejected.
A federal judge threw out the Montalvos' lawsuit last year, ruling that Michael's infectious HIV posed a direct threat to other students and that the school had reasonably tried to accommodate his disability.
The 4th U.S. Circuit Court of Appeals upheld the trial judge's ruling in February.
"The type of activity offered at U.S.A. Bushidokan emphasized sparring, attack drills and continuous body interaction with the result that participants frequently sustained bloody injuries, such as nose bleeds, cuts inside the mouth and external abrasions," the appeals court said.
"In the context of this hard-style karate, the risk of a student's transmitting HIV to another student was significant," the appeals court said.
Michael was born with the virus. His mother and sister have died from AIDS.
In the Supreme Court appeal, lawyers for the Montalvos said the decision to exclude Michael from the karate lessons had been made "without the benefit of objective medical opinion," and that medical testimony offered by the school "completely failed to objectively assess the level of risk." (Associated Press)