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Issue #212: January 15, 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, BBC, Boston Globe, Gannett News Bureau, Journal of Infectious Diseases, Journal of Traumatic Stress, The Lancet, Reuters, Science, United Press International.
Scientists say vaccine works in mice, but Indian study raises new questions
Clinton program offers jobs, insurance for disabled
PCP treatment can stop after HAART: study
Study ties violence against women, HIV
ACT UP challenges Whitman on needles
PPP seeks staff for syringe exchange
Man gets life for giving son HIV
Scientists say vaccine works in mice; Indian study raises questions
By taking a new approach to using a key HIV virus protein, University of Montana scientists have developed an experimental HIV vaccine that generates an immune response to a broader range of HIV virus subtypes than earlier vaccines - at least according to their tests in mice.
The work is still in a very early stage, but the approach opens up new ways for researchers to develop an effective vaccine that could be used worldwide to prevent the spread of HIV and AIDS, said Jack Nunberg, lead author of the study and director of University of Montana's biotechnology center. The research was reported in the January 15th issue of the journal Science.
Several HIV vaccine candidates have been tested in small groups of humans, but to date only one has U.S. Food and Drug Administration approval to be tested widely in a Phase III clinical trial in the United States. The vaccine, made by VaxGen Inc. and being tested at Philadelphia FIGHT, is made from genetically engineered forms of two subtypes of HIV. Tests of the vaccine began last year, and results are not expected for several years.
These earlier vaccine efforts focused on creating an immune response, or antibodies, to a protein known as gp120 that forms part of the coat of the HIV virus. Vaccines are made from weakened strains of a virus or parts of a virus that provoke the body to produce antibodies to neutralize a virus infection. But the gp120 protein-based vaccines did not create the hoped-for immune response.
Nunberg and his colleagues suspected another part of the HIV virus coat known as the gp41 protein might also be needed to awaken antibodies.
For HIV to infect a human cell, the HIV coat must bind to a CD4 cell receptor, and then fuse with the cell and inject the virus contents into it. The virus creates a sort of tunnel through which to do this.
David Montefiori, associate professor at Duke University Medical Center in Durham, N.C. and an AIDS vaccine researcher, likened the complex fusion process to a flower in which the gp120 is the flower petals and the gp41 is the stamen. When the gp120 "petals" come into contact with a human cell, they open up, and the gp41 "stamen" fuses the contact points and opens the tunnel so the virus can enter and infect the cell.
The opening of the petals lasts only a few seconds, which is why it has been hard to devise a vaccine that can act against HIV. "(These areas) become exposed for a very short period of time when the virus gets into the cell. That's not long enough for immune system to respond to it," Montefiori said.
Nunberg and his colleagues figured out a way to freeze open the "petals" and provoke antibodies to neutralize the HIV. The new concept is called a "fusion-competent" vaccine.
When tested in laboratory dishes against actual samples of HIV, the mouse antibodies were able to neutralize 23 of 24 strains of the virus.
"Our vaccine is the first which has elicited antibodies which can neutralize any virus from human patients," Nunberg said. ""To see that the response is very broad offers real hope that a broadly effective HIV vaccine might be developed."
"I think a lot of people will be rethinking how to develop vaccines now," Nunberg continued. "We've discovered a new way of thinking about developing an HIV vaccine that takes into account the underlying functioning of the coat protein."
"If this is real, it could represent a major breakthrough for AIDS vaccines," Montefiori said. "I was very excited when I first heard about it. This is the first time anyone has ever been able to generate these kinds of antibodies. This is very exciting. It could be a major breakthrough for HIV vaccine development because all of the efforts to date have not been able to generate anywhere near this magnitude of antibody response. And it is vital to develop a vaccine as this is the only way to stop the spread of AIDS worldwide."
"But it's still in an early stage of development, and there's a lot more to do" he added. "He's only done this in mice so far and you have to show that you can generate these antibodies in primates and ultimately in humans," he said. "A lot of times what you are able to do in the mouse you are unable to do in humans."
A vaccine containing cells would be dangerous to use as the cells themselves might be attacked by the immune system," Montefiore said. A viable vaccine would need to isolate the vital proteins from the virus.
"So the goal now is to find a way to open the virus without having the cells there," he continued. "But knowing that it's going to work as a vaccine if you can do it, that will get lots of people trying -- and we will eventually find a way."
Montefiori reviewed the study in a separate article in Science.
Nunberg added that more basic research needs to be done to understand how a vaccine might work. He also said the new vaccine concept will soon be tested in Rhesus monkeys, which are more similar to humans than mice.
But Nunberg will also have to refine the approach, according to Montefiori. Nunberg used whole monkey cells, which are unsuitable for use as vaccines because the immune system might react against entire cells -- something that could backfire. It is better to use the smallest piece of virus that can be used and still provoke a response.
More than 40 vaccines aimed at protecting against HIV infection are being tested in human volunteers. Many others have failed -- most of them aimed at the proteins on the surface of the virus.
Some vaccines use killed virus, or viruses that have been weakened, to prime the immune system. But most researchers believe that HIV is far too dangerous to try this approach.
While U.S. media was trumpeting the promising results of the Montana study, scientists who have mapped all the genes of an Indian subtype of HIV have announced that it had a frightening knack for swapping genes with other strains, which will make it extremely hard to develop a vaccine against it.
They found major differences in genes throughout the virus - not surprising in a virus known to mutate quickly. But it shows just how hard HIV is going to be to fight in the long run.
Writing in the Journal of Virology, the team at Johns Hopkins University in Baltimore and the AIDS Research Institute in Pune, India, said they had sequenced the HIV genes taken from six patients recently infected with the virus.
The most common strain of HIV in India is known as HIV-C. It is slightly different from the strain found in the United States, known as HIV-B. There are 10 known subtypes, named from A to J.
But subtype C is the most commonly transmitted form, both in India, which is a growing center of HIV infection, with an estimated 3 million to 4 million people infected with HIV, and in Africa, the current center of the AIDS epidemic.
Dr. Bob Bollinger of Johns Hopkins, who worked on the study, said researchers had found that the Indian C subtype was different from C subtypes found elsewhere in the world. And one patient had a virus that contained bits of both the A subtype and the C subtype.
"These recombinant viruses are becoming increasingly important and have a lot of importance for the design and testing of potential vaccines," Bollinger said in a telephone interview with Reuters Health Information Service.
"We may have to deal with not only multiple subtypes but with multiple subtypes that combine with each other."
Especially notable is that the surface envelopes of the different strains had different genes.
Most HIV vaccines being worked on target these surface proteins, because the outside layer of an invader is where the immune system looks first to check to see whether it should attack.
But the C strain, and the one combined A/C virus, had big genetic differences in their surface proteins. So a vaccine using these proteins might not work against different subtypes.
"We should probably look to other places in the virus for a vaccine," Dr. Stuart Ray, who led the study, said.
If a person has a recombinant virus - one that contains elements from two or more strains - it means that patient was infected with more than one subtype.
Unless he or she was infected with two at once, it means the patient was infected first with one, then later with another. As HIV is transmitted mostly through heterosexual sex in India and Africa, this in not an unlikely scenario.
But this is significant for vaccine efforts, Ray said. "If prior infection is not protective, what are our chances for making a vaccine?" he asked.
The idea behind a vaccine is to "prime" the immune system. That is the same reason that someone who is infected with a disease such as smallpox can never be reinfected with it.
But just like the influenza virus, HIV mutates into so many types that vaccination is made more difficult.
"That's why we need a new influenza vaccine every year," Bollinger said.
Bollinger and Ray said they hoped the study would help Indian health officials develop a suitable vaccine for their country and would shed light on where vaccine efforts elsewhere should be heading.
Most AIDS experts agree that a vaccine is the only answer to the epidemic.
But Ray said the findings indicated that any vaccine might have to be combined with some way of stimulating the immune system.
Clinton program offers jobs, insurance for disabled
President Clinton has proposed spending $2 billion over five years on programs to reduce the high jobless rate among disabled Americans by making it easier for them to work.
"We have to give people with disabilities the tools they need to succeed," Clinton said at a White House ceremony.
The plan, the latest in a series of proposals related to his budget request for fiscal year 2000, would allow disabled people who find work to continue receiving coverage under state and federal health care programs by buying into the programs.
"Americans should never have to choose between the dignity of work and the health care they need," Clinton said.
The health provisions, totaling $1.2 billion over five years, are to be introduced in the Senate by Republicans James Jeffords of Vermont and William Roth of Delaware and Democrats Ted Kennedy of Massachusetts and Daniel Patrick Moynihan of New York.
Clinton's plan also would provide a $1,000 tax credit to help cover the costs to the disabled of getting to and from work, personal assistance, and useful technology like voice-activated computers or mobile phones that connect directly to hearing aids.
"As anyone with a disability can tell you, it takes more than a job to enter the work force. Often, it takes successful transportation, specialized technology or personal assistance," Clinton said.
Clinton would also more than double government funding, up to $35 million, to accelerate the development of communications technologies that improve quality of life for the disabled.
This would include research into automatic captioning for people who are deaf, and speech recognition and eye tracking for people who cannot use a computer keyboard.
The programs were in response to statistics showing that while the U.S. economic boom has added 17.7 million new jobs in the last six years, the unemployment rate among all working-age adults with disabilities is nearly 75 percent.
According to current estimates, about 1.6 million working-age adults have a disability that leads to functional limitations and 14 million working-age adults have less severe but still significant disabilities.
Members of Congress who attended the event were optimistic that the Republican-controlled House and Senate would look favorably on the proposals.
The recommendations were the result of a task force that was created by Clinton last March in an executive order.
The AIDS lobbying group AIDS Action, in a press release, said that Clinton's proposal was "the first step toward enactment of [AIDS Action's] Reinventing Medicaid proposal."
AIDS Action said that included in the White House proposal is a demonstration project that would allow states to provide Medicaid coverage to low-income individuals with asymptomatic HIV disease and other potentially serious conditions. Under current Medicaid policy, an HIV-positive individual qualifies for benefits, including access to protease inhibitor drugs that can prevent the progression of HIV disease, only when they are diagnosed with full-blown AIDS.
AIDS Action has proposed a Reinventing Medicaid plan that would provide eligibility to HIV-positive individuals who are poor enough but not sick enough to be eligible for the program. Vice President Gore endorsed AIDS Action's plan in the spring of 1997 but, until today, no proposals were made and no action had been taken. The Back-to-Work proposal will be part of President Clinton's budget proposal and will require passage by Congress.
"This first step toward fairness in Medicaid is a victory for thousands of low-income people living with HIV," said AIDS Action executive director Daniel Zingale. "If automobile safety regulations followed the current model, air bags would only be required in cars that have already crashed."
Reinventing Medicaid to cover healthy HIV-positive Americans would save lives and save money, AIDS Action said. "Every major study of protease cocktails has shown that early treatment provides the best route for preventing the onset of illness. Moreover, the cost of providing drugs early would offset the exorbitant hospitalization and other medical costs that AIDS treatment incurs."
AIDS Action strongly supports the broad Back-to-Work proposal. "During the past several years, many Americans previously disabled by AIDS and forced onto Medicaid have benefitted from powerful new drugs that can enable them to return to work," the group said. "Still, because the income from a new job might disqualify Medicaid coverage but not provide adequate health coverage, some people with AIDS have been forced to choose between returning to work or access to care."
"This proposal parallels the needs of people with AIDS and the state of the epidemic," added Zingale. "No American should have to make a choice between work and health."
PCP treatment can stop after HAART: study
Dr. Margriet Schneider and colleagues from Utrecht, The Netherlands, have reported in The Lancet the results of a study into preventive drug treatment for Pneumocystis carinii pneumonia (PCP) in people infected with HIV.
They found that such drug treatment could be stopped safely after the patient's immune system had improved as a result of highly active antiretroviral therapy (HAART) directed against HIV.
PCP remains the most common opportunistic infection at the time of AIDS diagnosis in patients with HIV. Consequently, prophylactic drugs for prevention of PCP in HIV-infected patients have been recommended since 1989.
HAART has proved effective in decreasing replication of HIV and in increasing counts of CD4 T lymphocytes, which help the body to fight infection.
Since the frequency of opportunistic infections declines after HAART has been started, Dr. Schneider and colleagues wanted to find out whether prophylactic drugs for PCP could be stopped safely after a patient's CD4 cell count had reached more than 200.
The investigators enrolled 78 patients into their study: 62 were receiving prophylaxis for primary prevention of PCP (they had never had the disorder) and 16 patients for secondary prevention of PCP (they had had the disorder already). When prophylaxis was stopped, the average CD4 cell count for all patients was 347 cells. The lowest average CD4 cell count during prophylaxis was 79 cells.
Patients discontinued prophylaxis 9·8 months after they started HAART.
The researchers found that after a mean follow-up of 12·7 months, none of the patients had developed PCP.
"PCP prophylaxis or maintenance therapy can be stopped after the CD4 cell count has risen above 200 cells as a result of HAART," they write, adding that large-scale studies are needed before their results can be made into definite recommendations.
Meanwhile, another study has indicated that PCP is able to develop resistance against Mepron, a major treatment for the prevention of PCP.
Bactrim/Septra is the most common drug used to prevent and treat PCP. However, recent reports suggest that a small but increasing number of cases of PCP have appeared in people with HIV despite the use of Bactrim/Septra. Most of these individuals are then switched to Mepron (atovaquone).
Doctors in the U.S. and England have reported 4 cases of PCP in HIV-positive people taking Mepron. In at least 2 of the patients, resistance to Mepron was confirmed by genetic testing. All of the subjects had been using Mepron for between 2 and 15 months to prevent PCP at the time the drug failed.
Since PCP-causing microbes appear to need a single key mutation in order to develop resistance to Mepron, the research team suggests that another drug be used with it to avoid this problem. In the case of malaria, Mepron is in fact used successfully in combination with another drug to delay the appearance of resistance.
Study ties violence against women, HIV
A new report says women who have been mugged, raped or physically assaulted are at increased risk of becoming infected with HIV.
Researchers report that among inner city black women, those infected with HIV were two to five times more likely to have been victims of violence than uninfected females. The study, led by researchers at the University of California-San Francisco appears in the winter issue of the Journal of Traumatic Stress.
"Among women we talked to who were infected with HIV, those who had experienced victimization also reported more psychological distress, depression, and more physical symptoms," Dr. Rachel Kimerling of the University of California-San Francisco told United Press International.
The study team investigated 88 HIV-infected women, and a comparison group of 148 uninfected women, all black with similar backgrounds.
Two- thirds of the HIV-infected group reported having experienced extreme forms of violent victimization, Kimerling said.
"These results underscore the importance of acknowledging the experience of violent victimization in the prevention and treatment of HIV infection in women," Kimerling said. "A woman who is being physically battered by her male partner fears abuse consequences if she refuses sexual activity, or if she queries her partner about his sexual behavior, so there is this logical link that having been victimized might increase your risk of HIV."
Primary care and public health physicians need to recognize that previous victimization "puts you at a greater risk for HIV, but we don't know exactly why," she said.
"Women who've been assaulted or abused are more likely to engage in a number of behaviors that can increase their risk for HIV infection. Among these are substance abuse, sex in exchange for drugs or money, and increased likelihood of unprotected sexual encounters."
AIDS prevention programs should take this into and counsel such people more emphatically on ways to protect themselves, Kimerling said. She said that even if HIV programs "teach safe sex skills, women may be less able to put those skills into action if suffering from PTSD."
The rising incidence of HIV infection among inner-city, low-income blacks appears to be closely linked to environmental and cultural factors, such as drugs, crime, poverty and gender and racial discrimination, the researchers said. An HIV-infected woman's ability to "hold her own" in such an environment seems to be further impaired by depression, they said.
ACT UP challenges Whitman on needles
Led by ACT UP Philadelphia, over 200 people living with HIV/AIDS and AIDS advocates converged on New Jersey Governor Christine Whitman's "state of the state" address in January to dramatize the impact of Whitman's opposition to syringe exchange programs in the state.
Holding a Grim Reaper with Whitman's face on it and carrying four coffins - to represent the people who die statewide of AIDS contracted from dirty needles -- the group chanted "Christie Whitman, you can't hide. We charge you with genocide."
Officials would not allow the group to get closer than a block away from the site of Whitman's address.
As of September 1998, 37,163 people in New Jersey were diagnosed with AIDS, while another 13,761 tested positive for HIV, according to the state Health and Senior Services Department. To date, 23,519 people in New Jersey have died of AIDS.
According to ACT UP, there are 46,000 drug injectors in New Jersey in 1997 who do not have HIV, but they could contract it if a legal syringe program is not implemented.
Whitman spokesperson Peter McDonough admitted that Whitman's own Advisory Council on AIDS has endorsed needle exchange programs, but said that Whitman firmly believes the "state should not be an enabler here." He added that Whitman remains opposed to such programs because she believes "they are ineffective" and that "once a clean syringe is distributed, there is no way of stopping the user from sharing it with someone else."
If the program is to be monitored, the state must provide a place to shoot up, and Whitman does not want to encourage illegal drug use, McDonough said. Without monitoring, distributing needles only puts more of them into the population, McDonough said.
"She's firm in her opposition," McDonough said.
Earl Driscoll, a 41-year old former addict from Philadelphia who participated in the demonstration, said the only reason he is not HIV positive is because Philadelphia has supported Prevention Point, the local needle-exchange program.
"In the grips of an addiction, you do what you need to do to feel good. I wouldn't have stopped shooting drugs, even if there were no clean syringes," Driscoll said.
But with an exchange program, he showed up, turned in his old syringes for new ones and entered a treatment program when he was ready, he said.
"A dead addict can't recover," Driscoll said.
Activists say they are tired of hearing about politicians not wanting to send the wrong message.
"While our elected officials worry about their own political viability and expound, ad nauseam, about sending a bad message to children, they send their own very harmful message" of neglect, racism and hate, said Diana McCague, director of the Chia Project, which ran a needle-exchange program in New Brunswick.
McCague was arrested for distributing clean needles, but received a suspended jail sentence and community service.
There are two syringe-related bills in the New Jersey Senate, according to Gannett News Services. One would allow needle-exchange programs, and the other would deregulate the sale and possession of syringes. Both have made it through the Senate Health Committee.
But they face resistance, primarily from a Whitman veto threat.
"If this were a wealthy, elitist white issue and a virus that affected only them, you would have people tripping over each other trying to help them," said Sen. Joseph Vitale, D-Middlesex.
Vitale says he knows the governor will never sign the bills, but he is trying to get a consensus in the Legislature.
Last month, the Associated Press reported that the Dogwood Center, an AIDS research group, found that African Americans account for more than 60% of injection-related AIDS cases statewide, but only 15% of New Jersey's population. Similarly, Latinos account for 15% of injection-related HIV/AIDS cases, but represent only 10% of the state's population. The state Health Department reports that more than half of New Jersey's HIV/AIDS cases can be traced to dirty needles.
Meanwhile, a University of Connecticut study has indicated that the closing of a local needle exchange program has "crippled" the effort to combat new HIV infections among the area's needle addicts.
The study, led by Dr. Robert Broadhead. found that prior to the closing of the Windham, CT program, 14% of the area's intravenous drug users were using shared needles. After the program's closure, that figure jumped to 51%.
The researchers said that "Windham now faces even more problems: the progress the town made over the years in reducing drug users' risk behaviors has lost substantial ground."
The program operated with state funding from 1993 to 1997, when it was abruptly closed after a 2-year-old girl was pricked with a discarded needle, according to the Boston Globe.
Windham County State's Attorney Mark Solak dismissed the report, saying, "We have seen a substantial decrease in the number of discarded needles in the community's parks, playgrounds and wooded areas that are frequented by children and the streets in general." The state Department of Public Health & Addiction Services reports that Windham reported 19 AIDS cases in 1995, compared to eight cases last year.
Prevention Point Philadelphia, the city's syringe exchange and addiction support program, is looking for a staff person to help with its varied programs.
PPP is a public health non-profit agency committed to protecting the health and rights of drug users and sex workers in Philadelphia. It is one of the ten largest syringe exchange programs in the United States, and the only provider of syringe exchange in Philadelphia. In addition to the van-based needle exchange, it also provides medical care, HIV testing and counseling and educational/organizing meetings at its North Philadelphia center.
The new staff member will staff PPP's various exchange sites, maintain knowledge of state/national issues surrounding needle exchange, injection drug use, harm reduction and HIV/AIDS and educate exchangers, provide referrals to drug treatment, social services and medical care, and recruit and supervise volunteers.
PPP is seeking an individual with the ability to work with a wide variety of people, who has a bachelor's degree and good writing and communications skills, and has knowledge of Philadelphia neighborhoods and social services. Applicants who are Spanish/English bilingual are preferred.
The staff position includes health insurance and paid vacation benefits. To apply, submit resumes to: Julie Parr, MSW, Executive Director, Prevention Point Philadelphia, 333 West Girard Avenue, Philadelphia, PA 19123.
Man gets life for giving son HIV
A man who prosecutors said injected his son with HIV to avoid paying child support has been sentenced to life in prison by a judge who warned he is going to "burn in hell from here to eternity."
Brian Stewart, 32, of Columbia, Ill., stared straight ahead as Judge Ellsworth Cundiff handed down the maximum sentence for first-degree assault. The judge said he wished the sentence could have been stronger.
"My thought is injecting a child with the HIV virus really puts you in the same category as the worst war criminal," Cundiff said. "I believe when God finally calls you, you are going to burn in hell from here to eternity."
Stewart was convicted Dec. 6 of injecting AIDS-tainted blood into the boy, who was then 11 months old, during a hospital visit in 1992. The child, now 7, was diagnosed with AIDS in 1996. If the boy dies, Stewart could be tried for murder. Prosecutors said Stewart was trying to avoid child-support payments. Stewart, who worked as a hospital technician at the time, stole the blood from his workplace, prosecutors said.
At the sentencing, the boy's mother, identified only as Jennifer, tearfully read a statement from the boy in which he said: "I feel mad. I think he shouldn't ever be out of jail. He shouldn't have done this. Why did he do such a bad thing to me?"
Stewart's attorney Joseph Murphy, said he has already filed an appeal. "He's innocent," Murphy said.
The defense contended the boy could have contracted the virus a number of other ways, possibly from injection drug addicts living in the same house. However, the boy had never had a blood transfusion, and a medical exam found no evidence of sexual abuse.
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