Bulgarians, Italians to develop anti-AIDS vaccine for newborns

New face sculpting changes lives for HIV patients

Updated: 4/9/2006 5:55:00 AM
By: Ivanhoe Newswire

(BALTIMORE) - Facial wasting is often the term used to describe the sunken look that many people with HIV develop. It's not reserved for them alone, though. As people age, many lose the volume in their face, and there hasn't been much anyone could do about it until now.

Last year, George Sakellaris had a tough time going out in public. "Because I'm HIV-positive and the type of medication that I was taking, what was happening was what they call wasting," he said. "It was hard to look in the mirror and see that that was happening, and there was nothing I could do."

Sakellaris had lipoatrophy, fat loss that causes a sunken look in the face.

But dermatologist Ciro Martins, M.D., could do something -- with a new filler called Sculptra. "It stimulates your body to produce collagen to actually increase the thickness of the skin," he said.

Sculptra is polylactic acid tissue filler. Doctors inject it in up to 60 spots on the face.

"It's an unbelievable reaction. It's an unbelievable effect that you have on people's lives," said Dr. Martins, of Johns Hopkins Medicine in Baltimore.

Sculptra can also fight one of the most common signs of aging by restoring fat that's been lost over time. Dr. Martins said it works very well for loss of tissue as it occurs with aging, but he's most excited about its effect on HIV patients.

"It's a dramatic change in quality of life," he said. "People who are affected by lipoatrophy really feel like they have a red flag stamped all over the face saying that they're HIV-positive."

Before and after pictures show just how dramatic the change can be. "I look in the mirror, and I look healthy," Sakellaris said. "It was so dramatic, I couldn't stop crying actually." Now, he's ready to live life with his best face forward.

Up to half of all HIV patients on anti-retroviral drugs have lipoatrophy. The Sculptra injections last for about two years. After than, touch-ups may be needed. Insurance does not cover the cost.

Research summary

BACKGROUND: More than 1 million people are living with HIV in the United States and more than half a million have died after developing AIDS. Facial wasting is an important issue affecting the lives of people living with HIV. Facial wasting is one symptom of a syndrome called lipoatrophy. Lipoatrophy describes the loss of the soft layer of fat that sits just beneath the skin's surface.

Many times, people affected by the condition have well-controlled HIV disease, and are living healthy, productive lives. Yet, the appearance that comes with facial wasting often suggests the opposite and serves as a stigma.

ONE MAN'S ACCOUNT: George Sakellaris, who is HIV-positive, explains his own experience with facial wasting:

"It was pretty traumatic because what was happening is it just looked like I was constantly losing weight and sort of having that gaunt look. Even though I was working out and the rest of my body was proportioned, my face wasn't. It just became sunken. It was hard to look in the mirror and see that was happening and there was nothing I could do about it. I would have done anything to have my face look the way it did you know, four years ago."

FDA-APPROVED HOPE: There is now new hope for people living with lipoatrophy. Doctors are now using a product called Sculptra, which is poly-L-lactic acid, to fill out the face and restore a healthy appearance. Sculptra is a safe material that is injected below the surface of the skin in the area of fat loss. It provides a gradual and significant increase in skin thickness, improving the appearance of folds and sunken areas. A patient will generally receive four to five treatment sessions, where doctors inject Sculptra into the face. Up to 60 shots may be needed for the first session, but doctors say the number of shots decrease as the sessions continue. Ciro Martins, M.D., from Johns Hopkins University in Baltimore, says, "[Sculptra] gets deposited and then it stimulates your body to produce collagen to actually increase the thickness of the skin." A numbing cream is rubbed on the face to reduce the discomfort of the needle sticks. Thanks to that cream, many patients say they can barely feel the needles at all. Sculptra has been used in other countries since 1999. It is the first FDA-approved product of its kind for this condition.

COSMETIC USES? Sculptra may benefit more people than those living with HIV. As people age, many times they will develop facial fat loss. Dr. Martins says: "Lipoatrophy is very common. It's part of the aging process." Some dermatologists are now offering Sculptra as a way to fill in the face of older adults. However, Dr. Martins warns, "Most commonly for people who are looking for cosmetic correction of aging skin, they're going to have to have a combination of different things done to the skin to correct the different problems that are going on." In other words, Sculptra will only help people restore volume in the face associated with fat loss. It will not help sagging skin or wrinkles.

Clinical trial uses stem cells to treat HIV

04/08/06-04/10/06

About 70 HIV-positive adults in California are participating in a clinical trial that combines stem cell technology and genetic engineering to create what researchers call a “parallel immune” system to fight the disease, the San Francisco Chronicle reports. About half of the study participants have received injections of their own blood cells that have been engineered to contain a gene that blocks HIV. The goal is to create an array of long-lived cells that will fight HIV and outlast natural blood cells that are targeted by the virus.

The key to the therapy is inserting an engineered enzyme called ribozyme, which does not exist naturally in the body, into immune system cells. The enzyme destroys one of HIV’s key genes when the virus tries to copy itself, essentially preventing HIV from spreading in the body. Researchers attach the enzyme to an engineered mouse virus and expose human stem cells culled from bone marrow and the bloodstream to the virus. The mouse virus carries the enzyme into a cell, where it becomes part of the cell’s natural machinery and fortifies it against any attempts by HIV to infect it and begin making viral copies. The stem cells are then reinserted into the donor’s body, where they begin making numerous copies of immune system cells that are resistant to HIV.

Study participants must sit through two eight-hour sessions in which their blood is filtered to isolate the stem cells. Once the stem cells are removed, they are exposed to the ribozyme-carrying mouse virus, and three days later are injected back into the donors.

Lead researcher Ronald Mitsuyasu of the University of California, Los Angeles’s Center for Clinical AIDS Research and Education says that while he doesn’t think the approach will eventually replace standard antiretroviral therapy, it could be useful for HIV patients resistant to anti-HIV medications or those experiencing AIDS-related complications.

The clinical trial’s preliminary results will be reported in February 2007.

A similar clinical trial is being conducted by a research company in Sydney, Australia, that is owned by Johnson & Johnson. (The Advocate)

AIDS vaccine quest inspires cooperation for competitive researchers

BY LAURIE GOERING

CHICAGO TRIBUNE

JOHANNESBURG, South Africa — Each day, 13,000 people worldwide contract the virus that causes AIDS, the United Nations estimates. But two decades after the disease was first identified, scientists are still struggling to find a vaccine that could help contain its spread.

More than 70 AIDS vaccines have reached human trials. But only one has made it to advanced testing, and it has shown little sign of being effective, according to the International AIDS Vaccine Initiative, an advocacy organization.

“Making a vaccine has turned out to be much more difficult than we ever believed,” Barton Haynes, a leading vaccine researcher at Duke University, said back in 1999. Today, he and other equally frustrated scientists around the globe have abandoned their race to be first to create an effective vaccine and decided to try something new: cooperation.

Using a model pioneered by the Human Genome Project, AIDS researchers worldwide are joining forces and sharing labs, data, technology and funding to try to solve some of the most intractable mysteries surrounding HIV infection, with the aim of finally producing a vaccine that works.

With 40 million people now infected with the virus and 45 million more expected to get it by 2010 without intervention, “we all feel a sense of extraordinary urgency,” said Haynes, who leads one of the first two investigative centers created under the new Global HIV Vaccine Enterprise.

The centers, one based at the U.S. National Institute of Allergy and Infectious Disease and the other at Duke University, will pull together AIDS experts from throughout the world to do what Haynes calls “desperately needed” basic research on HIV infection.

At public clinics in South Africa, Malawi, Uganda and Tanzania, for instance, researchers will use RNA tests to try to find between 600 and 1,000 people who are in their first few days of HIV infection and who have not yet begun producing antibodies to the virus. Then they will track them in an effort to understand, for the first time, how the virus behaves in its first few days in the human body and how the body responds.

The data produced from such studies and other research information — including, potentially, the genetic sequencing of the virus itself — will be put on a public Web site for use by all AIDS researchers and members of the “virtual consortium.” Scientists will use the data to try to come up with new ideas for a vaccine, with the aim of getting vaccine candidates in human testing by 2009.

Basic research should help “tackle the big questions,” said Dr. Salim Abdool-Karim, director of the Center for the AIDS Program of Research in South Africa, one of the members of the new consortium. But “the roadblocks are so large and fundamental it’s impossible to predict when we’ll overcome this hurdle,” he said.

South Africa, with one of the largest AIDS epidemics in the world, has more than 5 million people infected with the virus, which means “South Africa and Africa have the most to gain” from a vaccine, said Carolyn Williamson, an AIDS researcher at the Institute of Infectious Disease and Molecular Medicine at the University of Cape Town.

South Africa already is involved in creating and testing potential AIDS vaccines, but its vaccine candidates — like most of those worldwide — show promise only in limiting the level of virus in the bloodstream of those who become infected, rather than curing their infection altogether.

The problem, scientists say, is that most vaccines — for diseases such as measles, for instance — help a newly infected person clear the virus or bacteria from the blood, ensuring the disease never develops. With HIV, however, there is no known case of an infected person ever clearing the virus from his body, which means an effective vaccine would have to prevent infection in the first place to be effective.

“We’re trying to do something that has not been accomplished for any vaccine yet,” Haynes said.

Nearly all the HIV vaccines currently in human trials — about 30 — focus on achieving a particular kind of immune response in the bloodstream to the virus. The first results from those studies should be released next year. The new research effort, however, will also focus on some neglected areas of study, including the possibility that a nasal-spray vaccine could stimulate the body’s mucus linings — including in the genitals — to neutralize HIV before it enters the bloodstream and causes infection.

The idea for that theory comes from a group of prostitutes in Africa who, despite regularly having unprotected sex with HIV-positive men, have never become positive for the virus themselves. Scientists, including Haynes, believe something in their mucus linings may neutralize the virus, keep it from entering the bloodstream or allow them to fight off infection.

The Global HIV Vaccine Enterprise, first proposed by two dozen HIV vaccine researchers in 2003 and backed by the Bill and Melinda Gates Foundation, now has the financial support of the G8 developing countries, including the United States, which is investing around $500 million a year in AIDS vaccine development efforts.

Who would ultimately own and produce any vaccine the group produces remains to be seen, researchers said. But the goal is “a vaccine that becomes a public good,” Abdool-Karim said.

Researchers warn that finding such a vaccine will take time, even with a cooperative effort.

“The vaccine will not be a ‚Äureka!’ moment. It will be a very slow process,” Williamson said.

South African scientists say that even a lesser vaccine that keeps the level of the virus low in people who become infected would be a help. Although it would not necessarily save their lives, it could help lower the likelihood they pass the disease to others, slowing the rapid transmission of the disease in sub-Saharan Africa.

Essentially such a virus would mean “not curing individuals but curing a population,” said Dr. Clive Gray of the National Institute of Communicable Diseases in Johannesburg.

The Associated Press

Researchers at the National Institute of Allergy and Infectious Disease (NIAID), a component of the National Institutes of Health (NIH), have identified a critical human cell surface molecule involved in infection by Kaposi's sarcoma herpesvirus (KSHV), the virus that causes Kaposi's sarcoma and certain forms of lymphoma. Kaposi's sarcoma is a major cancer associated with HIV/AIDS, and it typically manifests as multiple purple-hued skin lesions.

Washington, D.C. - infoZine - In the March 31, 2006 issue of "Science", NIAID research fellow Johnan Kaleeba, Ph.D. and senior investigator Edward A. Berger; Ph.D., describe how the molecule xCT is a major gateway that KSHV uses to enter human cells. The molecule may also play a role in the development of Kaposi's sarcoma and other syndromes associated with the virus.

The natural function of xCT in the body is to transport molecules necessary for protecting against stress into cells. When cells are stressed, they express more xCT on their surfaces. Of note, this sort of stress can be caused by KSHV itself. This suggests that the virus may facilitate its own infectivity and dissemination in the body by inducing a physiological state that results in increased numbers of its own receptor.

"The advancement of knowledge achieved in this study highlights the outstanding intramural research that takes place here on the NIH campus," says Elias A. Zerhouni, M.D., NIH director.

"Understanding the mechanisms of cell entry of Kaposi's sarcoma herpesvirus is a landmark achievement in and of itself," says NIAID director Anthony S. Fauci, M.D. "But the connection between the virus and expression of its own receptor on a cell is even more provocative because it might change the way we think about KSHV-associated diseases and their treatment."

Although less common in the United States now than early in the AIDS pandemic, Kaposi's sarcoma is still the most common cancer associated with HIV infection. Prior to the AIDS pandemic, it was an obscure disease. First identified as a multi-pigmented skin disease by a Hungarian doctor named Moritz Kaposi in 1872, it was considered to be quite rare -- a medical curiosity usually found in particular populations such as older Italian men, transplant patients and young men in certain parts of sub-Saharan Africa. But then at the dawn of the AIDS pandemic in the early 1980s, the small purplish Kaposi's sarcoma skin lesions began appearing on the bodies of young American men, many of whom went on to develop opportunistic infections.

Dr. Berger became interested in KSHV because of his interest in how viruses enter cells. A decade ago, his research team was the first to identify CXCR4 as one of the coreceptors that allows HIV to gain entry into cells of the immune system. This discovery quickly led to the identification by Dr. Berger's group and several other research teams of CCR5 as the other HIV coreceptor.

By applying the same technology used to identify CXCR4, Drs. Kaleeba and Berger ultimately identified the protein xCT as the receptor that can make cells permissive for KSHV fusion.

The NIAID discovery may lead to new avenues for treating KSHV, says Dr. Berger. Moreover, their finding should enable scientists to determine whether levels of xCT determine disease severity. It also will allow researchers to study whether the expression of xCT on cells varies among different groups of people and whether these variations are genetic or environmental. This research may ultimately explain why certain groups are more at risk for Kaposi's sarcoma.

"Our finding provides a new perspective on the disease," says Dr. Kaleeba, who is originally from Uganda where Kaposi's sarcoma accounts for at least 10 percent of known tumors. "Hopefully this will be the beginning of exciting new directions in this field, as it is likely to provide a useful framework for integration of the cell biology and epidemiology of this clinically important virus.