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 information in this issue include AIDS Treatment News, Associated Press, Cell, Nature Medicine, Reuters, San Francisco Chronicle, Wall Street Journal.
Women still missed in HIV diagnoses; ACT UP protests at National Women's Conference
Government settles hemophiliac case
Activists protest suspension of CMV trials
CD4 study reinforces calls for early treatment
HIV weak spot exposed in protein study
Flu vaccine safe for HIV+ kids: study
Study blasts abstinence programs
Women's HIV infection often is missed because doctors aren't recognizing that vaginal infections, yeast infections of the mouth and throat and cervical cancer are part of the disease.
A recent federal report noted that while the AIDS death rate in men dropped by 15% in the first six months of 1996, deaths in women increased by 3%.
In Philadelphia, the picture is equally grim. From 1995 to 1996, the number of deaths in men dropped by 27%, while number of deaths of women remained the same. The percentage of AIDS deaths that were women rose from 14.7% to 19.3%. These figures have still not been officially released by the Philadelphia Department of Health.
"Why did Health Commissioner Estelle Richman convene a expert advisory panel on lowering infection rates in babies? The only time health officials pay attention to women is when they are pregnant. Why no special reports or plans to save local women with HIV?" asked Jennifer DePiero of ACT UP Philadelphia.
Meanwhile, a Chicago consortium has found illness-causing cytomegalovirus active in blood and secretions well before women with HIV progress to AIDS. The research found cytomegalovirus was the root cause of vaginal infections in 41 percent of the women tested.
Also at the third National Conference on Women & HIV, a University of Southern California team announced that it had detected unusual types of breast cancer in young HIV-infected women, including rare metaplastic carcinoma.
Although breast cancer rates haven't yet increased in women with HIV, other AIDS-defining cancers are on the rise, such as melanoma, multiple myeloma and anal cancer, said Dr. Alexandra Levine, leader of USC's research team and director of the university's Norris Cancer Center.
And with antiviral AIDS drugs leaving the immune system of HIV-infected women "not quite normal, we may be seeing ever-increasing epidemics of cancer," Levine predicted.
While the rate of AIDS deaths in men declined 15 percent in the first six months of last year, the rate for women increased 3 percent, according to figures at the federal Centers for Disease Control in Atlanta.
AIDS is the third-leading killer of American women ages 25-44 and the No. 1 killer of African-American women that age. Women constitute the fastest-growing segment of the U.S. population to become HIV-infected.
"AIDS-related cancers tend to be more aggressive than cancers in non-HIV positive women," Dr. Janet Blair of the Los Angeles County health department told reporters.
While men survive about 23 months with Kaposi's sarcoma -- the first malignancy recognized with AIDS -- women survive just nine months, she said.
The difference "may reflect delayed access to medical care," or doctors' lack of recognition, she said.
The breast cancer and CMV results were among the first presented from the Women's Interagency HIV Study, known as WIHS, begun in 1992 and funded by the National Institutes of Health in Washington.
The four-day conference drew more than 1,500 scientists, infected women and health policy experts, including a group of women from Philadelphia. More than 120 HIV-infected activists, including many from Philadelphia, interrupted a news conference to demand a national plan to address the unique problems of women, including African-Americans and Hispanics.
"What is the government doing for me? Where is the plan and the funding to save my life?" asked Jeannine M. Scott, a mother of three from Philadelphia.
The women also criticized the state of women's access to cutting edge treatments, which effectively makes it easier for them to get AZT to prevent transmission to their babies than to get drug treatment for themselves.
"The number of deaths of women with HIV in this country is in free-fall," said Dawn Acero of ACT UP. "While men's deaths are decreasing, women are dying by the thousands. Where is the national initiative to stop this tragedy?"
"I have not heard one word from public health officials addressing the urgent need for a massive effort to turn this death rate around. Now there is a national conference where people will talk about what is really needed, and the top public health official in our country, Donna Shalala, decided that the conference wasn't important enough to even show up."
Activists stress that the government has acted quickly and decisively to attempt to prevent perinatal transmission of HIV from mother to infant, while continuing to ignore the needs of HIV+ women.
"When the results of ACTG 076 came out, there was a chain reaction of intense, national activity to publicize the results and develop programs based on the study," recalls ACT UP Philadelphia's Julie Davids. "We know what we need to do to save women s lives. We need to do it now!"
"Women with HIV have challenging lives. We need housing, we need jobs, we need an end to the violence that plagues our lives and communities. But I expect that the health and research systems of this government will play their part, too," added Us Women's Anne Capone.
Activists stress that their efforts will not cease with the end of the Conference. "We will not let this issue drop. More and more women are dying every day. We demand a comprehensive plan, backed with real dollars, by Labor Day," said Asia Russell.
"It's going to be a long, hot summer for Shalala if she doesn't get busy saving women's lives," Russell said.
Clarification: In last week's fastfax, we quoted a member of the Philadelphia HIV Commission as being concerned that the first organizational meeting of a new Commission women's caucus was originally scheduled for a date on which many women with HIV would be attending the National Conference on Women and HIV. We have since been informed that the meeting was re-scheduled to a week later in order to allow more women to participate. The meeting will be held on Wednesday, May 14th at the offices of the Philadelphia HIV Commission, Fidelity Building, 123 South Broad Street, Room 2284 on the 22nd Floor, from 3:00 to 5:00 p.m.
Government settles hemophiliac case
Four medical companies have reached pacts with the federal government and several state governments that could clear the way for a multimillion-dollar lawsuit settlement over blood-clotting medications that resulted in HIV infection for many hemophiliacs in the 1980s.
Baxter International Inc., Bayer AG of Germany, Rhone-Poulenc Rorer Inc., and Japan's Green Cross Corp. had previously agreed to a settlement in which they would pay $100,000 each to the families of hemophiliacs who contracted HIV disease from blood-clotting medications called Factor VIII and Factor IX.
However, there has been a question about whether the U.S. or state governments would receive money from the settlement fund to reimburse them for any payments they had made to care for the hemophiliacs.
Now, the U.S. and 20 states have agreed to forgo any share of the settlement fund, the companies said. A spokesman for the companies said the agreements will clear the way for payments to at least 4,000 of an estimated 6,000 hemophiliacs expected to participate in the settlement. The spokesman said the companies still are negotiating with other states.
The settlement is scheduled to go before U.S. District Judge John F. Grady in Chicago for a fairness hearing soon to determine if the agreement should go forward. The settlement covers AIDS or HIV infection contracted during the early 1980s, before the medications were treated to remove viruses.
Activists protest suspension of CMV trials
by John S. James
AIDS Treatment News #270
1-800-TREAT-A
AIDS treatment activists have learned that plans for future Phase III trials of RS-79070, an oral prodrug of ganciclovir, had been suspended by Hoffmann-La Roche, apparently due to concern that there are no longer enough new cases of CMV retinitis to justify the expense of continuing development.
A smaller phase II trial, which is still recruiting, will continue. The decision was made at Roche offices in Basel.
RS-79070 is a chemical relative of ganciclovir which can be readily absorbed orally, and then is changed to ganciclovir in the bloodstream. It provides much higher blood levels of ganciclovir than the currently approved oral drug, which is poorly absorbed. Because of its lower efficacy, the oral ganciclovir which is now available cannot be used for induction (the initial high-dose treatment of CMV retinitis), and is controversial for maintenance (long-term treatment of active CMV disease after induction) and prophylaxis (prevention of CMV disease in persons who are at risk).
RS-79070 may replace intravenous treatments or ocular implants for CMV disease, with a pill which is taken once a day (twice a day for the first three weeks of treatment for the induction phase). Because it delivers ganciclovir to the body, it will have the same basic side effects of that drug.
Unfortunately, current drug-development rules require large and expensive phase III trials before RS-79070 can be marketed -- even though (1) this drug serves only as a better delivery vehicle for supplying ganciclovir orally, (2) a less effective oral ganciclovir is already approved, and (3) the smaller phase II trial now recruiting will show whether or not RS-79070 is comparable to intravenous ganciclovir for induction treatment of CMV retinitis.
Project Inform, in San Francisco, which first learned of the decision to suspend development of the large trials required for marketing, is deeply concerned because it has been hearing quite good anecdotal reports about RS-79070 from physicians and patients -- and also because of reports that the number of new cases of CMV retinitis may be starting to rise again, due to more treatment failures after longer-term use of the new combination anti-HIV regimens. GMHC (Gay Men's Health Crisis, in New York), organized a letter of protest to Roche involving treatment activists from around the world, which was to be delivered to the company in early May.
CD4 study reinforces calls for early treatment
The immune system's army of CD4+ T cells not only declines in overall size during the course of HIV disease, but also becomes progressively less diverse as specific CD4+ T cells programmed to fight different invaders are lost, according to researchers at the National Institute of Allergy and Infectious Diseases (NIAID).
These depleted cell types may not be immediately restored by therapies such as antiretroviral drugs or interleukin-2 (IL-2) that can increase an HIV-infected person's overall CD4+ T cell count. Rather, such therapy, at least in the short-term, appears to boost only the cells that were present when therapy began. The findings are reported in the May 1997 issue of Nature Medicine.
"Our findings argue for treatment early in disease, before elements of the immune system are significantly depleted," says senior author H. Clifford Lane, M.D., NIAID's clinical director. "Our data also suggest that drugs to prevent opportunistic infections may remain important even for patients with CD4+ T cell counts that are rapidly increasing in response to therapy, because these individuals may be missing part of their CD4+ T cell repertoires."
Adds co-lead author Mark Connors, M.D., of the NIAID Laboratory of Immunoregulation, "The loss of CD4+ T cells is a qualitative phenomenon as well as a quantitative one. In other words, a CD4+ T cell count of 200 per cubic millimeter (mm3) of blood during the natural history of HIV infection may be very different from a CD4+ T cell count of 200/mm3 in the context of therapy. Depletions in the CD4+ T cell repertoires of HIV-infected people and hence the reduced ability of their immune systems to recognize certain antigens are probably key to the development of immunodeficiency in these people."
The current findings shed light on an observation reported by Dr. Lane and his colleagues in the mid-1980s: HIV-infected people often lose their ability to respond to "remote recall antigens": substances to which one was exposed in the past, such as the antigens in a tetanus vaccine. The new data suggest that this decreased responsiveness is due to a loss of specific CD4+ T cell types, which scientists refer to as "clones."
"A loss of CD4+ T cell clones, and the resulting "holes" in a person's CD4+ T cell repertoire, rather than an active immunosuppressive phenomenon, may explain why an HIV-infected person becomes unresponsive to remote recall antigens," says co-lead author Joseph A. Kovacs, M.D.
HIV weak spot exposed in protein study
For the first time scientists have exposed a weak spot in the HIV virus, which may lead to new drugs that will keep it from invading and destroying human cells.
The discovery is based on high-resolution pictures of an "envelope" protein fragment on the surface of HIV that the virus uses to get inside cells after it attaches to them.
"Basically, we made a finding in how the virus affects cells," says Dr. David Chan, a postdoctoral fellow in structural biology at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts. "The envelope protein resides on the surface of the virus and plays a crucial role in HIV infection."
Chan explains that the virus is surrounded by a membrane that contains genetic material. "In order for the virus to infect cells, it has to get outside its own membrane and penetrate the human membrane. So there are two membranes through which the virus' genetic material must pass."
Key to this process, says Chang, is the envelope protein, one part of which is called gp120, which allows the virus to attach itself to human cells. Another structural unit is gp41, which lets the virus fuse itself to the target cell -- a human T cell, part of the immune system.
"For the envelope protein to function, the two parts -- gp120 and gp41 -- have to interact with each other," Chang says. "There's a very clear way in which these two parts interact."
Here is where the Whitehead team's pictures come in. First the researchers biochemically dissected the protein and grew crystals from a solution containing gp41's two cell fusion fragments. Using x-ray crystallography, they bombarded the crystals with x-rays and then computer converted the scatter pattern of rays into a sharp image of gp41's molecular structure.
The images revealed a compact bundle containing deep cavities that could be key targets for new drugs. It is at these cavities that the fusion fragments make a kind of ball and socket connection.
Of almost equal importance is the finding that the cavity structure of gp41 does not change even though the virus often mutates. This means the cavity region may be an unchanging target for new drugs that would, therefore, be effective against many HIV strains.
"Our structure, combined with data from other laboratories, suggests that a small molecule constructed specifically to block this interaction could stop fusion and prevent the virus from entering cells," says Dr. Peter S. Kim in whose Whitehead laboratory the discovery was made.
"Until we saw the images, we didn't know that these cavities existed. They could be key targets for the development of new antiviral drugs," Kim says.
Flu vaccine safe for HIV+ kids: study
Influenza vaccination does not intensify HIV infection in children, a clinical study shows.
Recent data suggest that immune activation temporarily increases HIV replication. Since increased viral burden is now known to be associated with more rapid disease progression, there is great concern that routine vaccinations could speed progression to AIDS in children.
These fears can be laid to rest, according to a study by Richard M. Donovan and colleagues of the Henry Ford Hospital and Children's Hospital of Michigan, Detroit.
Donovan evaluated HIV RNA levels and CD4 counts before and after influenza vaccination of 39 children with HIV infection.
The children, whose median age was 5.5 years, had a median CD4 percentage of 30 percent before and 29 percent after vaccination (P=0.86). They had a median CD4 count of 861 cells/(micro)L before and 663 cells/(micro)L after vaccination (P=0.10).
Their median HIV RNA level was 1042 copies/50 (micro)L before and 1,042 copies/50 (micro)L after vaccination (P=0.67).
A four-fold increase in plasma HIV RNA occurred in one of the children.
Donovan noted that these results mirror those seen in a similar cohort of nine children examined before and after DPT vaccination.
"There was no evidence of significant changes in CD4(+) cell count or an increase in the HIV viral load after influenza or DPT vaccinations in this pediatric cohort," they wrote.
Study blasts abstinence programs
A study released last month by two public policy groups blasted abstinence-only sex education programs, claiming the curricula are dangerous and are being illegally promulgated in California.
The report, issued by the Public Media Center of San Francisco and the Applied Research Center of Oakland, states that one-third of the state's school districts say they have been pressured to modify sex education programs, mainly by religious organizations.
The two groups also said that abstinence-only sex education curricula violated the state education code because they deny students information about contraception, fail to mention that condoms may reduce the risk of HIV infection and depict gays and people of color in an unflattering light.
The state education code requires schools to emphasize abstinence from sex and intravenous drug use as the best way to avoid HIV infection. It also requires schools to provide students with accurate information on condoms and forbids the stereotyping of people with AIDS.
"The curricula we studied were so riddled with omissions and errors that they were life-threatening," said Hunter Cutting, a spokesman for the Applied Research Center. "They implied that the HIV virus could pass through latex condoms -- and that might discourage sexually active teens from using (condoms)."
Cutting said abstinence-only sex programs often promote negative stereotypes of gays and people of color. The report cited a popular abstinence-only text known as Sex Respect as particular egregious in this regard.
Whites were presented in positive scenarios, the report said, while African Americans were largely absent or depicted in negative situations, such as at a sexually transmitted disease clinic.
But supporters of abstinence- only education defended the programs. Pauline Holmes, a San Francisco psychotherapist who specializes in a Christian clientele, said abstinence-only programs are effective.
"Even President Clinton is espousing them because they work," she said. "The fact is that children cannot emotionally handle sexual activity, and there is no denying the tremendous downside of disease and pregnancy. Condoms and contraceptives are by no means foolproof."
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