blog.bioethics.net

FOR IMMEDIATE RELEASE
Tue 7-Mar-2006
CONTACT:Peter Taback, amfAR, 212 806 1602, peter.taback@amfar.org
Newest amfAR Grants Announced: Understanding HIV Infection at the Start
amfAR Researchers Examine the First Events After HIV Enters the Body
NEW YORK (March 7, 2006) What happens after HIV enters the body? Under which circumstances does HIV transmission lead to infection? What chain of events occurs at the beginning of infection? amfAR, The Foundation for AIDS Research, announced nearly $1 million dollars in new grants and fellowships for scientists seeking answers to these questions – answers many scientists believe will lead to improved methods to prevent infection.
“Not enough is known about the earliest moments of HIV’s interaction with the human body,” said Dr. Rowena Johnston, amfAR’s director of research. “The more we know, the better equipped we will be to develop a broader range of interventions – drug treatments used before or shortly after exposure to the virus, a microbicide or even a vaccine – to break the link in the chain of events leading from HIV transmission to established infection.”
One of amfAR’s new grantees is Dr. Benjamin Chen, of the Mount Sinai School of Medicine in New York. Dr. Chen will study HIV-1 infection of mucosal lymphocytes and tissue in the intestines, one of the first places where the virus invariably wipes out immune cells.
“There is great mystery surrounding the viral predilection for depleting immune cells in the gut,” Dr. Chen said. “If we can work out why the virus homes in on these cells, we may be able to develop targeted strategies to obstruct this process.” Chen’s study is one of 10 projects designed to better understand, mitigate and prevent HIV transmission and infection. Some involve the investigation of gene therapy and possible vaccine and microbicide candidates.
Newly announced amfAR fellow Dr. Hoshang Unwalla of the City of Hope National Medical Center in Duarte, California, will design a novel gene therapy as a potential barrier to infection. This technique is intended to prevent HIV from infecting cells in part by taking advantage of a series of events inside the cell that is set off by the virus itself.
“Gene therapy has the potential to improve treatment for a wide range of diseases, including HIV,” said Dr. John Rossi, who will serve as a mentor for Dr. Unwalla’s study. “By supporting Dr. Unwalla, amfAR is backing the development of a truly innovative technique that might one day not only broaden HIV patients’ treatment options but could eventually have even more far-reaching implications for the treatment of other viral infections and some cancers.”
With a grantmaking philosophy that values novel approaches to the unanswered questions surrounding HIV, amfAR consistently deploys grants and fellowships at the forefront of AIDS research. Finding new ways to prevent HIV infection is one of the goals of amfAR’s research program.
The Foundation has focused prior funding cycles on vaccine and microbicides research and on mucosal HIV transmission. amfAR funded the earliest research on DNA vaccines, one of the most promising concepts being pursued today in the quest for an AIDS vaccine. More recently, amfAR supported research leading to the first detailed description of a broadly neutralizing antibody, which could be critical in the design of an AIDS vaccine, as well as pioneering research using a new technology known as siRNA to develop a microbicide.
amfAR, The Foundation for AIDS Research, is one of the world’s leading nonprofit organizations dedicated to the support of AIDS research, HIV prevention, treatment education, and the advocacy of sound AIDS-related public policy. Since 1985, amfAR has invested close to $250 million in its programs and has awarded grants to more than 2,000 research teams worldwide.
GRANTS
Benjamin Chen, M.D., Ph.D.
Mount Sinai School of Medicine, New York, NY
HIV-1 infection of mucosal lymphocytes and tissue explants: Regardless of whether HIV enters the body via the vagina or rectum, immune cells in the gut (including the rectum and small and large intestine) rapidly become infected, followed by a massive loss of gut immune cells. Dr. Chen hypothesizes that certain gut cells may produce chemical signals that guide the virus to the gut. He will tag individual viruses with a fluorescent protein that will allow him to see movement of the virus towards the gut cells, in a test tube environment.
Thomas Hope, Ph.D.
Northwestern University, Chicago, IL
Interaction of HIV with the macaque female genital tract: Events that occur within the first 48 hours of HIV being deposited in the vagina are not clearly understood. Dr. Hope plans to use a novel technology developed in his laboratory to visualize individual viruses as they cross the lining of the macaque vagina and cervix to infect underlying tissues. This project will provide much-needed information on the earliest events in HIV infection, particularly those that happen within minutes or a few hours of HIV entering the vagina. This information might ultimately be used to develop strategies to prevent infection in the vagina.
Dale McPhee, Ph.D.
St. Vincent’s Institute. Fitzroy, Australia
HIV-1 transmission and replicative fitness: The strains of HIV that initially infect people may differ in important respects from strains of HIV that are found later during the course of infection. Dr. McPhee hypothesizes that the specific viruses responsible for initial infection may differ in their relative fitness, or ability to reproduce. By finding generalizable characteristics of the viruses responsible for establishing infection, scientists may be better able to design an AIDS vaccine that specifically targets the types of virus that are most likely to cause initial infection.
Leonard Moise, Ph.D.
Brown University, Providence, RI
Targeting an HIV multi-epitope vaccine to dendritic cells: One problem in developing an AIDS vaccine is ensuring that the vaccine generates an immune system response that is strong enough to overcome the virus. Dr. Moise plans to test a vaccine concept that has the potential to increase vaccine strength up to 1000-fold, by chemically linking a small portion of HIV - known to generate an important but weak immune system response - to dendritic cells. Dendritic cells form part of the immune system – they play an important role in increasing the ability of HIV to infect a large number of cells, but have the potential, if manipulated correctly, to play a key role in fighting the virus.
Eva Rakasz, Ph.D.
University of Wisconsin, Madison, WI
Female genital ulcer as a portal of HIV entry: Women who have sexually transmitted infections (STIs) like herpes or syphilis are at greatly increased risk of becoming infected with HIV, yet why this is so is not completely understood. One possibility is that the immune cells fighting those infections in the vagina provide ideal targets for incoming HIV. Dr. Rakasz plans to test, in monkeys, another hypothesis, that the ulcers commonly associated with STIs like herpes or syphilis acts as portals through which the virus can gain access to tissues underneath the surface of the vagina and thereby establish generalized infection in the body.
Manish Sagar, M.D.
Harvard University, Boston, MA
Understanding the properties of transmitted HIV-1 variants: The strains of HIV that initially infect people represent only a small portion of all the viruses circulating in the body of the transmitting partner. Dr. Sagar hypothesizes that viruses responsible for initiating a new infection are specifically well-suited to reproduce in the types of cells with which the virus first comes into contact. He will determine whether the total amount and/or density of sugars on the surface of HIV are associated with the likelihood of infecting a new person. This knowledge will increase out understanding of factors that influence sexual HIV transmission and how initial infection sets the stage for the course of disease.
FELLOWSHIPS
Gabriel Birrane, Ph.D. / Mentor: John Ladias, M.D.
Beth Israel Deaconess Medical Center, Boston, MA
Molecular mechanisms of the HIV-1 co-receptor CCR5 function: In the vast majority of cases, initial infection with HIV requires that the virus interact with a protein found on the surface of some human cells called CCR5. Researchers are investigating ways of preventing this interaction and thus preventing infection altogether. Dr. Birrane has identified proteins found inside cells that regulate how much CCR5 is found on a cell’s surface and where. By understanding how the presence of CCR5 is regulated, Dr. Birrane may discover a new way in which scientists could devise therapies that would decrease the amount of CCR5 on the cell surface and thus decrease the chances that the cell could become HIV infected.
Richard Haaland, Ph.D. / Mentor: Eric Hunter, Ph.D.
Emory University, Atlanta, GA
Virologic correlates of subtype-A HIV transmission: HIV can be divided into families or subtypes, some of which occur more frequently in different regions of the world. Subtype-A HIV is one of the HIV viruses found commonly in Africa. Dr. Haaland wants to understand which characteristics of this HIV subtype, especially in the surface proteins of the virus, make it more likely to be transmitted to a sex partner than other viruses. There appear to be important differences that might predict infectiousness of subtype A viruses as opposed to subtype B viruses, which are more commonly found in North America, Europe and Australia. Understanding the characteristics of viruses which viruses can more readily infect a sex partner will help in efforts to develop an AIDS vaccine.
Hoshang Unwalla, Ph.D. / Mentor: John Rossi, Ph.D.
City of Hope National Medical Center, Duarte, CA
Designing inducible Pol II systems for RNA interference of HIV: Dr. Unwalla plans to develop a gene the

- by alta charo on Mar 21, 2006 at 3:36 PM | link

Your links to the Farber article don't seem to work. Here it is.
I remember that when Joyce Ann Hafford died, the local paper carried her story. It seems that the doctors who conducted the study and were supposed to oversee her care ordered bloodwork, whose results indicated that her liver was being severely damaged. This was known to be a possible effect of the drug. The report went into her chart and there was no action taken. You'd better believe that's lawsuit territory.

- by Laura(southernxyl) on Mar 21, 2006 at 11:34 PM | link

Here's another article:
"NIH's documents suggest Hafford's life might also have been spared if the drug had been stopped when the first liver problems showed up in her blood work two weeks before death.
"'This case was particularly unfortunate b/c (because) the PI (principle investigative doctor) didn't stop drug when grade 3 liver enzymes were reported,' Dr. Jonathan Fishbein, NIH's chief of good research practices, told Tramont in an August 2003 e-mail.
"Fishbein, who is seeking federal whistleblower protection after raising concerns about NIH's practices, told AP that Hafford's death is attributable to a bigger problem in government research.
"'This is not just a clinical trial issue, this is a healthcare issue. The public expects that diagnostic test results are promptly evaluated and acted on, if need be,' Fishbein said. 'Sadly, this is but one example where an assessment was not done quickly and it cost this young mother her life.'"
Well, I'm filled with confidence now, aren't you?

- by Laura(southernxyl) on Mar 21, 2006 at 11:44 PM | link

Laura,
Don't get me wrong: I think there was gross negligence in the Hafford case. It's just that Farber's article uses the Hafford case as a springboard for far more sweeping claims. If she had stuck with the Hafford case, and the irregularities within the NIH and its increasingly intimate relations with pharmaceutical companies, it would have been a persuasive article. Instead, she saw fit to muddy the waters by dragging in her 'AIDS denialist' hobbyhorse.

- by Stuart Rennie on Mar 22, 2006 at 11:50 AM | link

I agree. I started skimming when she went into the AIDS thing.
But if NIH and CDC and so forth want credibility where AIDS and other legitimate issues are concerned they have to clean up their act. Remember CDC coming out with statistics about handgun deaths, like they are the result of some new viral epidemic? How about painting a big "I HAVE A POLITICAL AGENDA" sign on the building. Get it over with.
The Hafford case seemed to me to have overtones of Tuskegee. She thought the doctors were looking out for her welfare, while in reality her welfare wasn't even on their radar screen. I think the docs running the studies and the docs overseeing the docs are possibly losing sight of the ultimate goal of all of this stuff: to help actual human beings. Or if not even that, they could remember "first do no harm".

- by Laura(southernxyl) on Mar 23, 2006 at 10:07 PM | link

There is a lot more discussion of the Harper's article by Celia Farber at
http://www.aidstruth.org/

- by Dr. Phillip S. Duke on Apr 10, 2006 at 7:30 PM | link

And a lot more published since 2002 by me at www.redflagsdaily.com, including this one. President Thabo Mbeki and Peter Duesberg versus Robert Gallo/John Moore are not alone in this. - I welcome comment direct at anita@theallens.co.za.
Lively Stir, But Little Sign Of Enlightenment
By Anita Allen
Journalist Celia Farber's article "Out of Control: AIDS and the corruption of medical science," in the March issue of Harper's magazine, is creating a lovely stir. (1) Let's hope that fairness, accuracy and balance prevail. Lickety-split, there was a rebuttal of the Farber piece by no less than Robert Gallo, MD, John P. Moore, PhD, et al, listing 16 misleading statements, 25 false statements, 10 unfair statements and five indicating bias. (2) It's being circulated via the Internet as a "draft for Harper's magazine and public distribution."
I hesitate to quote from it because not only is the subject sub judice in my country with court cases pending, but because giving it any exposure is too much.
As far as the science goes, it’s the science of Peter Duesberg, PhD, professor of molecular and cell biology at the University of California, versus the science of Gallo/Moore and associates. Gallo is director of the Institute of Human Virology, University of Maryland; Moore, professor of microbiology and immunology at Cornell University’s Weill Medical College.
On another level, Nathan Geffen, a spokesperson for the South African pro-antiretrovirals activist organization, Treatment Action Campaign (TAC), signed the rebuttal, along with representatives of the Gay Men's Health Crisis, Treatment Action Group, and Marijuana Policy Project.
At 35 pages, the rebuttal is unreadable and unpublishable. It replaces allegedly misleading, false, unfair and biased statements, with more of the alleged same — and one wonders what contribution the marijuana project made. Gallo was invited by South African President Thabo Mbeki to serve on his AIDS Advisory Panel. Gallo turned down the invitation — rudely — and alienated many in the process. He wouldn't defend his science face-to-face; now he tries to do it in Harper's.
Good luck to Harper’s editor. No number of alleged discrepancies negate the central theme of Farber's report — the human story of people like Farber's Joyce Ann Hafford, unknowingly (and as Farber recounts, illegally) on trials of highly toxic drugs, which no manufacturer claims can cure AIDS or halt the replication of HIV.
Gallo et al would have us believe it is "beyond doubt" that death from HIV/AIDS is a far greater risk than antiretroviral (ARV) side effects. Well, in an average six years, everyone who goes the route of ARVs is dead. The shortest death I know of is 19 days. Some people don’t like the odds, especially when they hear there's no statistics on the longevity of those who choose other treatments and the relative effects of treatments.
Gallo et al can't afford to go that way. How can they advocate trials that would negate their science? As for the public alliance of Gallo/Moore/TAC et al — old arguments, obsolete science, nothing new. They're chasing the wrong enzyme.
In the quiet halls of science, winds of change are blowing.
Read past Red Flags columns by Celia Farber here.
References:
The New York Times. "An Article in Harper's Ignites a Controversy Over HIV," March 13, 2006.
http://www.tac.org.za. Click on "Rebuttal."

- by Anita Allen on Apr 29, 2006 at 9:28 AM | link

I've read both the Farber article and the response by Gallo et al. The research, from thousands of articles by AIDS/HIV scientists all over the globe, not just that of Gallo and his friends, completely obliterates Farber's contentions. Very embarassing for her, and for Harpers as well. I guess the idea these days is to put forth your politics, regardless of what the facts say, but the facts from all the clinical trials say that taking an anti-retroviral will save your life if you have AIDS. There was no "rebuttal" from Farber or any of her supporters, just pathetic attempts to save face.

- by Brian Osborne on Jun 4, 2006 at 11:31 PM | link