AIDS: USC Says Prof Pin Wang Has Invented 'A Virus That Hunts Down HIV-Infected Cells'

By Dennis Romero
From http://blogs.laweekly.com/

Sometimes the best way to catch a mouse is the natural way -- with a cat.

Using that philosophy, it seems, USC chemical engineering Professor Pin Wang might have just hit one out of the park. The university announced today that he "created a virus that hunts down HIV-infected cells."

You read that right. A living thing that preys on another living thing (but one we don't care for). Of course, it's a little more complicated than that:

Wang's "lentiviral vector" virus doesn't actually eat or destroy HIV-infected cells, but it does mark them for the kill, accomplished by drugs that can then better target them for destruction.

As is, HIV drugs can destroy healthy cells too. USC:

The process is analogous to the military practice of "buddy lasing" - that is, having a soldier on the ground illuminate a target with a laser to guide a precision bombing strike from an aircraft.

In the lab, Wang's virus has been known to destroy 35 percent of HIV-infected cells. Not a cure yet, but not bad at all.

HIV as you've never seen it before

Sandrine Ceurstemont, video producer
from: http://www.newscientist.com/


It's hard to visualise what something as small and complex as HIV actually looks like. But now Ivan Konstantinov and his team from Visual Science have created the most-detailed 3D model of the virus to date (see video above). An image of this visualisation just won first place in the 2010 International Science and Engineering Visualization Challenge, sponsored jointly by the journal Science and the National Science Foundation (NSF).

The model contains 17 different viral and cellular proteins and the membrane incorporates 160 thousand lipid molecules, of 8 different types, in the same proportions as in an actual HIV particle. It denotes the parts encoded by the virus's own genome in orange, while grey shades indicate structures taken into the virus when it interacts with a human cell.

To create the visualisation, the team consulted over 100 articles on HIV from leading science journals and talked to experts in the field. Then they reconstructed viral proteins from X-rays before assembling the structure of an entire HIV particle. The final appearance was achieved by experienced designers and 3D graphics specialists. Thanks to software and algorithms developed by the company, the model was completed in about three months.

The illustration was featured on the cover of Nature Medicine in September 2010, as part of a special issue prepared by the Global HIV Vaccine Enterprise. But because of the high resolution of the model, Konstantinov says it is suitable for a range of formats, from posters to animations and interactive applications for web and mobile platforms. For the moment, they plan to use it in schools and to popularise science research. But this model, and others created by the company such as a visualisation of the swine flu virus, are sure to be useful in medical research.

If you would like to see other winning entries from the 2010 International Science and Engineering Visualization Challenge, check out our online gallery here.

In Australia, Another Hint of HIV Cure

Posted by Michael_Byrne
From http://www.motherboard.tv/

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If you remember last December, the first ever human went from HIV-positive to HIV-negative. The “cure,” a stem cell transplant fortified with a particular sort of HIV resistant strain, was grueling, brutal, and risky. The patient had a one-in-three chance of dying from each of the two transplants. The therapy took two years, and it’s certainly pricey enough that you can be sure the insurance companies of the world will lobby hard to make sure it never gets beyond being classified as “experimental.”
What I’m saying is that curing someone in this case doesn’t indicate that we’ve found a cure. But, researchers in Australia at the Walter and Eliza Hall Institute announced this week via a new study that the answer could be as simple as pumping up your body’s immune system. The potential cure has to do with a hormone called interleukin-7, which “reinvigorates” the body’s immune system when it’s faced with something as hard-core as HIV, or Hepatitis or Tuberculosis.
From ScienceDaily today:

“Viruses such as HIV and hepatitis B and C overwhelm the immune system, leading to establishment of chronic infections that are lifelong and incurable,” [study author] Dr Pellegrini said. “Despite tremendous efforts, long-lived immune responses for some of these viruses are ineffective, because the body is so overrun by virus that the immune system, in particular T cells, just give up trying to battle the infection. Some people have coined the phrase ‘immune exhaustion’ to explain the phenomenon. Our approach is to discover some of the mechanisms that cause this immune exhaustion, and manipulate host genes to see if we can boost the natural immune response in order to beat infection.”

So far, Pellegrini have been able to eliminate an HIV-like infection from a mouse using interleukin-7. The key seems to lie in a gene called SOCS-3 that interleukin-7 shuts off.

“In an overwhelming infection, SOCS-3 becomes highly activated and suppresses the immune response, probably as a natural precaution to prevent ‘out-of-control’ responses that cause collateral damage to body tissue,” Dr Pellegrini said. “In the case of these overwhelming infections, the immune system effectively slams on the brakes too early, and the infection persists.”

So the general idea then is convincing your body that it can do the damn thing and take the infection down. Sort of a pep talk and a Sparks for your T cells.

Advance in Quest for HIV Vaccine

By MARK SCHOOFS

From: http://online.wsj.com/

HIV research is undergoing a renaissance that could lead to new ways to develop vaccines against the AIDS virus and other viral diseases.

In the latest development, U.S. government scientists say they have discovered three powerful antibodies, the strongest of which neutralizes 91% of HIV strains, more than any AIDS antibody yet discovered. They are now deploying the technique used to find those antibodies to identify antibodies to influenza viruses.

Mark Schoofs discusses a significant step toward an AIDS vaccine, U.S. government scientists have discovered three powerful antibodies, the strongest of which neutralizes 91% of HIV strains, more than any AIDS antibody yet discovered.

The HIV antibodies were discovered in the cells of a 60-year-old African-American gay man, known in the scientific literature as Donor 45, whose body made the antibodies naturally. The trick for scientists now is to develop a vaccine or other methods to make anyone's body produce them as well.

That effort "will require work," said Gary Nabel, director of the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases, who was a leader of the research. "We're going to be at this for a while" before any benefit is seen in the clinic, he said.

The research was published Thursday in two papers in the online edition of the journal Science, 10 days before the opening of a large International AIDS Conference in Vienna, where prevention science is expected to take center stage. More than 33 million people were living with HIV at the end of 2008, and about 2.7 million contracted the virus that year, according to United Nations estimates.

Vaccines, which are believed to work by activating the body's ability to produce antibodies, eliminated or curtailed smallpox, polio and other feared viral diseases, so they have been the holy grail of AIDS research.

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Last year, following a trial in Thailand, results of the first HIV vaccine to show any efficacy were announced. But that vaccine reduced the chances of infection only by about 30%, and controversy erupted because in one common analysis the results weren't statistically significant. That vaccine wasn't designed to elicit the new antibodies.

The new discovery is part of what Wayne Koff, head of research and development at the nonprofit International AIDS Vaccine Initiative, calls a "renaissance" in HIV vaccine research.

Antibodies that are utterly ineffective, or that disable just one or two HIV strains, are common. Until last year, only a handful of "broadly neutralizing antibodies," those that efficiently disable a large swath of HIV strains, had been discovered. And none of them neutralized more than about 40% of known HIV variants.

But in the past year, thanks to efficient new detection methods, at least a half dozen broadly neutralizing antibodies, including the three latest ones, have been identified in peer-reviewed journals. Dennis Burton of the Scripps Institute in La Jolla, Calif., led a team that discovered two broadly neutralizing antibodies last year; he says his team has identified additional, unpublished ones. Most of the new antibodies are more potent, able to knock out HIV at far lower concentrations than their previously known counterparts.

HIV is a highly mutable virus, but one place where the virus doesn't mutate much is where it attaches to a particular molecule on the surface of cells it infects. Building on previous research, researchers created a probe, shaped exactly like that critical site, and used it to attract only those antibodies that efficiently attack it. That is how they fished out of Donor 45 the special antibodies: They screened 25 million of his cells to find 12 that produced the antibodies.

Donor 45's antibodies didn't protect him from contracting HIV. That is likely because the virus had already taken hold before his body produced the antibodies. He is still alive, and when his blood was drawn, he had been living with HIV for 20 years.

While he has produced the most powerful HIV antibody yet discovered, researchers say they don't know of anything special about his genes that would make him unique. They expect that most people would be capable of producing the antibodies, if scientists could find the right way to stimulate their production.

Dr. Nabel said his team is applying the new technique to the influenza virus. Like HIV, influenza is a highly mutable virus—the reason a new vaccine is required every year.

"We want to go after a universal vaccine" by using the new technique to find antibodies to a "component of the influenza virus that doesn't change," said NIAID director Anthony Fauci. In principle, Dr. Fauci said, the technique could be used for any viral disease and possibly even for cancer vaccines.

Some of the new HIV antibodies discovered over the past year attack different points on the virus, raising hopes that they could work synergistically.

In unpublished research, John Mascola, deputy director of the Vaccine Research Center, has shown that one of Dr. Burton's antibodies neutralizes virtually all the strains that are resistant to the antibody from Donor 45. He also found the reverse: The antibody from Donor 45 disables HIV strains resistant to one of Dr. Burton's best antibodies. Only one strain out of 95 tested was resistant to both antibodies, he said. Dr. Mascola is one of the authors of Thursday's papers.

Researchers say they plan to test the new antibodies, likely blended together in a potent cocktail, in three broad ways.

First, the antibodies could be given to people in their raw form, somewhat like a drug, to prevent transmission of the virus. But they would likely be expensive and last in the body for a limited time, perhaps weeks, making that method impractical for all but specialized cases, such as to prevent mother-to-child transmission in childbirth.

The antibodies could also be tested in a "microbicide," a gel that women or gay men could apply before sex to prevent infection.

The antibodies might even be tried as a treatment for people already infected. While the antibodies are unlikely to completely suppress HIV on their own, say scientists, they might boost the efficacy of current antiretroviral drugs.

Dr. Nabel said that the Vaccine Research Center has contracted with a company to produce an antibody suitable for use in humans so that testing in people could begin.

A second way to use the new research is to stimulate the immune system to produce the antibodies. Jonas Salk injected people with a whole killed polio virus, and virtually everyone's immune system easily made antibodies that disabled the polio virus. But for HIV, the vast majority of antibodies are ineffective. Now, scientists know the exact antibodies that must be made—those found in Donor 45 and in Dr. Burton's lab, for example. So researchers need "a reverse engineering technology" to find a way to get everyone to produce them, said Greg Poland, director of vaccine research at Mayo Clinic in Rochester, Minn.

That's what scientists at Merck & Co. have done. In a study published this year in the Proceedings of the National Academy of Sciences, the Merck Scientists knew that an old antibody, weaker than the newly discovered ones, attaches to a particularly vulnerable part of HIV. They created a replica of that piece of the virus to train the immune system to produce antibodies aimed at that exact spot. It was a painstaking process, requiring researchers to add chemical bonds to stabilize the replica so that it wouldn't collapse and lose its shape. Eventually, Merck was able to make experimental vaccine candidates capable of spurring guinea pigs and rabbits to produce antibodies that home in on the target site and neutralize HIV. Those vaccines weren't nearly powerful enough, but, said Dr. Koff, Merck's research provides a "proof of principle" that reverse engineering can work for the much stronger new antibodies.

There are other potential pitfalls. There is evidence that Donor 45's cells took months or possibly even years to create the powerful antibodies. That means scientists might have to give repeated booster shots or devise other ways to speed up this process.

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Finally, there are experimental methods that employ tactics such as gene therapy. Nobel laureate David Baltimore is working on one such approach.

His team at the California Institute of Technology in Pasadena, Calif., has stitched genes that code for antibodies into a harmless virus, which they then inject into mice. The virus infects mouse cells, turning them into factories that produce the antibodies.

Write to Mark Schoofs at mark.schoofs@wsj.com

Man appears free of HIV after stem cell transplant

By Jacquelyne Froeber
From: http://www.cnn.com/

A 42-year-old HIV patient with leukemia appears to have no detectable HIV in his blood and no symptoms after a stem cell transplant from a donor carrying a gene mutation that confers natural resistance to the virus that causes AIDS, according to a report published Wednesday in the New England Journal of Medicine.

The patient underwent a stem cell transplant and since, has not tested positive for HIV in his blood.

"The patient is fine," said Dr. Gero Hutter of Charite Universitatsmedizin Berlin in Germany. "Today, two years after his transplantation, he is still without any signs of HIV disease and without antiretroviral medication."

The case was first reported in November, and the new report is the first official publication of the case in a medical journal. Hutter and a team of medical professionals performed the stem cell transplant on the patient, an American living in Germany, to treat the man's leukemia, not the HIV itself.

However, the team deliberately chose a compatible donor who has a naturally occurring gene mutation that confers resistance to HIV. The mutation cripples a receptor known as CCR5, which is normally found on the surface of T cells, the type of immune system cells attacked by HIV.

The mutation is known as CCR5 delta32 and is found in 1 percent to 3 percent of white populations of European descent.

HIV uses the CCR5 as a co-receptor (in addition to CD4 receptors) to latch on to and ultimately destroy immune system cells. Since the virus can't gain a foothold on cells that lack CCR5, people who have the mutation have natural protection. (There are other, less common HIV strains that use different co-receptors.)

People who inherit one copy of CCR5 delta32 take longer to get sick or develop AIDS if infected with HIV. People with two copies (one from each parent) may not become infected at all. The stem cell donor had two copies.

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While promising, the treatment is unlikely to help the vast majority of people infected with HIV, said Dr. Jay Levy, a professor at the University of California San Francisco, who wrote an editorial accompanying the study. A stem cell transplant is too extreme and too dangerous to be used as a routine treatment, he said.

"About a third of the people die [during such transplants], so it's just too much of a risk," Levy said. To perform a stem cell transplant, doctors intentionally destroy a patient's immune system, leaving the patient vulnerable to infection, and then reintroduce a donor's stem cells (which are from either bone marrow or blood) in an effort to establish a new, healthy immune system.

Levy also said it's unlikely that the transplant truly cured the patient in this study. HIV can infect many other types of cells and may be hiding out in the patient's body to resurface at a later time, he said.

"This type of virus can infect macrophages (another type of white blood cell that expresses CCR5) and other cells, like the brain cells, and it could live a lifetime. But if it can't spread, you never see it-- but it's there and it could do some damage," he said. "It's not the kind of approach that you could say, 'I've cured you.' I've eliminated the virus from your body." Health.com: 10 questions to ask a new partner before having sex

Before undergoing the transplant, the patient was also found to be infected with low levels of a type of HIV known as X4, which does not use the CCR5 receptor to infect cells. So it would seem that this virus would still be able to grow and damage immune cells in his body. However, following the transplant, signs of leukemia and HIV were absent.

"There is no really conclusive explanation why we didn't observe any rebound of HIV," Hutter said. "This finding is very surprising."

Hutter noted that one year ago, the patient had a relapse of leukemia and a second transplant from the same donor. The patient experienced complications from the procedure, including temporary liver problems and kidney failure, but they were not unusual and may occur in HIV-negative patients, he said.

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Researchers including Hutter agree that the technique should not be used to treat HIV alone. "Some people may say, 'I want to do it,'" said Levy. A more logical -- and potentially safer -- approach would be to develop some type of CCR5-disabling gene therapy or treatment that could be directly injected into the body, said Levy.

Less invasive options to alter CCR5 could be on the horizon within the next five years, said Levy. "It's definitely the wave of the future," he said. "As we continue to follow this one patient, we will learn a lot."

One drug that's currently on the market that blocks CCR5 is called maraviroc (Selzentry). It was first approved in 2007 and is used in combination with other antiretroviral drugs. Health.com: Who's most at risk for STDs?

In 2007, an estimated 2 million people died from AIDS, and 2.7 million people contracted HIV. More than 15 million women are infected worldwide. HIV/AIDS can be transmitted through sexual intercourse, sharing needles, pregnancy, breast-feeding, and/or blood transfusions with an infected person. Health.com:What should I do if the condom breaks?

"For HIV patients, this report is an important flicker of hope that antiretroviral therapy like HAART [highly active antiretroviral therapy] is not the endpoint of medical research," Hutter said.

Copyright Health Magazine 2009

Acne drug prevents HIV breakout (w/ Video)

From: http://www.physorg.com/news188240911.html

Enlarge

This is Janice E. Clements, Ph.D., Mary Wallace Stanton Professor of Faculty Affairs, Vice Dean for Faculty, and Professor of Molecular and Comparative Pathobiology at the Johns Hopkins University School of Medicine. Credit: Johns Hopkins Medicine

Johns Hopkins scientists have found that a safe and inexpensive antibiotic in use since the 1970s for treating acne effectively targets infected immune cells in which HIV, the virus that causes AIDS, lies dormant and prevents them from reactivating and replicating.

The drug, minocycline, likely will improve on the current treatment regimens of HIV-infected patients if used in combination with a standard drug cocktail known as HAART (Highly Active Antiretroviral Therapy), according to research published now online and appearing in print April 15 in The Journal of Infectious Diseases. "The powerful advantage to using minocycline is that the virus appears less able to develop drug resistance because minocycline targets cellular pathways not viral proteins," says Janice Clements, Ph.D., Mary Wallace Stanton Professor of Faculty Affairs, vice dean for faculty, and professor of molecular and comparative pathobiology at the Johns Hopkins University School of Medicine.

"The big challenge clinicians deal with now in this country when treating HIV patients is keeping the virus locked in a dormant state," Clements adds. "While HAART is really effective in keeping down active replication, minocycline is another arm of defense against the virus."

Unlike the drugs used in HAART which target the virus, minocycline homes in on, and adjusts T cells, major immune system agents and targets of HIV infection. According to Clements, minocycline reduces the ability of T cells to activate and proliferate, both steps crucial to HIV production and progression toward full blown AIDS.

Janice E. Clements, Ph.D., Mary Wallace Stanton Professor of Faculty Affairs, Vice Dean for Faculty, and Professor of Molecular and Comparative Pathobiology at the Johns Hopkins University School of Medicine, discusses her team’s discovery that a safe, inexpensive antibiotic will improve on the current treatment regimens of HIV-infected patients. Credit: Johns Hopkins Medicine

If taken daily for life, HAART usually can protect people from becoming ill, but it's not a cure. The HIV virus is kept at a low level but isn't ever entirely purged; it stays quietly hidden in some immune cells. If a person stops HAART or misses a dose, the virus can reactivate out of those immune cells and begin to spread.

The idea for using minocycline as an adjunct to HAART resulted when the Hopkins team learned of research by others on rheumatoid arthritis patients showing the anti-inflammatory effects of minocycline on T cells. The Hopkins group connected the dots between that study with previous research of their own showing that minocycline treatment had multiple beneficial effects in monkeys infected with SIV, the primate version of HIV. In monkeys treated with minocycline, the virus load in the cerebrospinal fluid, the viral RNA in the brain and the severity of central nervous system disease were significantly decreased. The drug was also shown to affect T cell activation and proliferation.

"Since minocycline reduced T cell activation, you might think it would have impaired the immune systems in the macaques, which are very similar to humans, but we didn't see any deleterious effect," says Gregory Szeto, a graduate student in the Department of Cellular and Molecular Medicine working in the Retrovirus Laboratory at Hopkins.

"This drug strikes a good balance and is ideal for HIV because it targets very specific aspects of immune activation."

The success with the animal model prompted the team to study in test tubes whether minocycline treatment affected latency in human T cells infected with HIV. Using cells from HIV-infected humans on HAART, the team isolated the "resting" immune cells and treated half of them with minocycline. Then they counted how many virus particles were reactivated, finding completely undetectable levels in the treated cells versus detectable levels in the untreated cells.

"Minocycline reduces the capability of the virus to emerge from resting infected T cells," Szeto explains. "It prevents the virus from escaping in the one in a million cells in which it lays dormant in a person on HAART, and since it prevents virus activation it should maintain the level of viral latency or even lower it. That's the goal: Sustaining a latent non-infectious state."

The team used molecular markers to discover that minocycline very selectively interrupts certain specific signaling pathways critical for T cell activation. However, the antibiotic doesn't completely obliterate T cells or diminish their ability to respond to other infections or diseases, which is crucial for individuals with HIV.

"HIV requires T cell activation for efficient replication and reactivation of latent virus," Clement says, "so our new understanding about minocyline's effects on a T cell could help us to find even more drugs that target its signaling pathways."

Provided by Johns Hopkins Medical Institutions

Man appears free of HIV after stem cell transplant

By Jacquelyne Froeber
From http://www.cnn.com/

A 42-year-old HIV patient with leukemia appears to have no detectable HIV in his blood and no symptoms after a stem cell transplant from a donor carrying a gene mutation that confers natural resistance to the virus that causes AIDS, according to a report published Wednesday in the New England Journal of Medicine.

The patient underwent a stem cell transplant and since, has not tested positive for HIV in his blood.

"The patient is fine," said Dr. Gero Hutter of Charite Universitatsmedizin Berlin in Germany. "Today, two years after his transplantation, he is still without any signs of HIV disease and without antiretroviral medication."

The case was first reported in November, and the new report is the first official publication of the case in a medical journal. Hutter and a team of medical professionals performed the stem cell transplant on the patient, an American living in Germany, to treat the man's leukemia, not the HIV itself.

However, the team deliberately chose a compatible donor who has a naturally occurring gene mutation that confers resistance to HIV. The mutation cripples a receptor known as CCR5, which is normally found on the surface of T cells, the type of immune system cells attacked by HIV.

The mutation is known as CCR5 delta32 and is found in 1 percent to 3 percent of white populations of European descent.

HIV uses the CCR5 as a co-receptor (in addition to CD4 receptors) to latch on to and ultimately destroy immune system cells. Since the virus can't gain a foothold on cells that lack CCR5, people who have the mutation have natural protection. (There are other, less common HIV strains that use different co-receptors.)

People who inherit one copy of CCR5 delta32 take longer to get sick or develop AIDS if infected with HIV. People with two copies (one from each parent) may not become infected at all. The stem cell donor had two copies.

While promising, the treatment is unlikely to help the vast majority of people infected with HIV, said Dr. Jay Levy, a professor at the University of California San Francisco, who wrote an editorial accompanying the study. A stem cell transplant is too extreme and too dangerous to be used as a routine treatment, he said.

"About a third of the people die [during such transplants], so it's just too much of a risk," Levy said. To perform a stem cell transplant, doctors intentionally destroy a patient's immune system, leaving the patient vulnerable to infection, and then reintroduce a donor's stem cells (which are from either bone marrow or blood) in an effort to establish a new, healthy immune system.

Levy also said it's unlikely that the transplant truly cured the patient in this study. HIV can infect many other types of cells and may be hiding out in the patient's body to resurface at a later time, he said.

"This type of virus can infect macrophages (another type of white blood cell that expresses CCR5) and other cells, like the brain cells, and it could live a lifetime. But if it can't spread, you never see it-- but it's there and it could do some damage," he said. "It's not the kind of approach that you could say, 'I've cured you.' I've eliminated the virus from your body." Health.com: 10 questions to ask a new partner before having sex

Before undergoing the transplant, the patient was also found to be infected with low levels of a type of HIV known as X4, which does not use the CCR5 receptor to infect cells. So it would seem that this virus would still be able to grow and damage immune cells in his body. However, following the transplant, signs of leukemia and HIV were absent.

"There is no really conclusive explanation why we didn't observe any rebound of HIV," Hutter said. "This finding is very surprising."

Hutter noted that one year ago, the patient had a relapse of leukemia and a second transplant from the same donor. The patient experienced complications from the procedure, including temporary liver problems and kidney failure, but they were not unusual and may occur in HIV-negative patients, he said.

Researchers including Hutter agree that the technique should not be used to treat HIV alone. "Some people may say, 'I want to do it,'" said Levy. A more logical -- and potentially safer -- approach would be to develop some type of CCR5-disabling gene therapy or treatment that could be directly injected into the body, said Levy.

Less invasive options to alter CCR5 could be on the horizon within the next five years, said Levy. "It's definitely the wave of the future," he said. "As we continue to follow this one patient, we will learn a lot."

One drug that's currently on the market that blocks CCR5 is called maraviroc (Selzentry). It was first approved in 2007 and is used in combination with other antiretroviral drugs. Health.com: Who's most at risk for STDs?

In 2007, an estimated 2 million people died from AIDS, and 2.7 million people contracted HIV. More than 15 million women are infected worldwide. HIV/AIDS can be transmitted through sexual intercourse, sharing needles, pregnancy, breast-feeding, and/or blood transfusions with an infected person. Health.com:What should I do if the condom breaks?

"For HIV patients, this report is an important flicker of hope that antiretroviral therapy like HAART [highly active antiretroviral therapy] is not the endpoint of medical research," Hutter said.

Copyright Health Magazine 2009

Bananas prevent HIV infection

Chemicals found in bananas are better at preventing HIV than two current synthetic anti-HIV drugs, according to new study.

By Bryan Nelson
From http://www.mnn.com/

BANANA POWER: A banana a day to keep HIV away? (Photo: ian_ransley/Flickr)

Your favorite oblong fruit might be even healthier than you realized. According to The Gazette (Montreal) newspaper, a new study has found that chemicals commonly found in bananas are as potent in preventing HIV as two synthetic anti-HIV drugs. Researchers say the findings could lead to a cheap new component for applied microbicides that prevent sexual transmission of HIV.

The miracle substance in bananas is called BanLec, a type of lectin, which are the sugar-binding proteins found in a variety of plants. Scientists have long been interested in lectins because of their ability to halt the chain reaction that leads to certain viral infections. In the case of BanLec, it works by binding naturally to the sugar-rich envelope that encases the HIV virus, thus blocking its entry into the body.

"The problem with some HIV drugs is that the virus can mutate and become resistant, but that's much harder to do in the presence of lectins," said lead author Michael D. Swanson. "Lectins can bind to the sugars found on different spots of the HIV-1 envelope, and presumably it will take multiple mutations for the virus to get around them."

Swanson and his colleagues noted that even modest success in developing BanLec into a vaginal or anal microbicide could save millions of lives. In fact, 20 percent coverage with a microbicide that is only 60 percent effective against HIV may prevent up to 2.5 million HIV infections in three years. Furthermore, a BanLec ointment would be much cheaper to produce and distribute than most current anti-retroviral medications that require the production of synthetic components.

One thing's for sure: new ways of stopping the transmission of HIV are desperately needed. Condoms are effective, but they are often used incorrectly or inconsistently, and in many cultures and developing countries women are not always in control of their sexual encounters. The introduction of a cheap, long-lasting, self-applied ointment derived naturally from bananas could change all of that.

HIV vaccine hailed as 'historic milestone' in fight against Aids

A vaccine has reduced the chance of HIV infection in humans for the first time, in what the scientific community has hailed a breakthrough in the fight against Aids.

By Rebecca Smith and Alastair Jamieson

HIV virus particles Photo: GETTY IMAGES

The combination of two vaccines that has previously failed to produce a response on their own has cut the risk of becoming infected with HIV by more than 31 per cent.

It is the first time in human trials that a vaccine has protected against the virus which leads to Aids.

The trial was conducted in 16,000 volunteers in Thailand, with half receiving the combination of the two vaccines and the other half receiving dummy jabs.

Dr. Anthony Fauci, director of the United States National Institute of Allergy and Infectious Diseases, warned the development was "not the end of the road," but said he was surprised and very pleased by the outcome.

"It gives me cautious optimism about the possibility of improving this result" and developing a more effective Aids vaccine, he said. "This is something that we can do."

The trial was carried out by the U.S. Military HIV Research Program and the Thai Ministry of Public Health.

Seth Berkley, chief executive and president of The International Aids Vaccine Initiative (IAVI) said: “The outcome is very exciting news and a significant scientific achievement.

“It’s the first demonstration that a candidate Aids vaccine provides benefit in humans. Until now, we’ve had evidence of feasibility for an AIDS vaccine in animal models. Now, we’ve got a vaccine candidate that appears to show a protective effect in humans, albeit partially.”

The challenge will now to be improve the efficiacy of the vaccines to a level which clear protection so it can be licensed for widespread use.

Deborah Jack, Chief Executive of the National Aids Trust, said: "These vaccine trial results are very good news - ultimately vaccines are the most effective way by far of tackling serious infectious disease. And with over two million new HIV infections a year this option is desperately needed.

"Obviously there is much more work to do with these promising findings, but they justify the continuing investments and efforts of the international community, including the UK Government, to develop a vaccine."

Wayne Koff, IAVI Senior Vice President for Research and Development, said: “At the very least, these results give researchers a platform on which to improve and to validate animal models and assays, and a way to attract new investment and creative energy to the field of Aids vaccine R&D.”

"Today marks a historic milestone," said Mitchell Warren, executive director of the Aids Vaccine Advocacy Coalition, an international group that has worked toward developing a vaccine.

"It will take time and resources to fully analyse and understand the data, but there is little doubt that this finding will energise and redirect the Aids vaccine field.

Even a partially effective vaccine could have a big impact. In 2007, two million died of Aids according to the United Nations agency UNAIDS.

Colonel Jerome Kim, who helped lead the study for the US Army, which was also involved in the trial, said: "It is the first evidence that we could have a safe and effective preventive vaccine."

The Thailand Ministry of Public Health conducted the study, which used strains of HIV common in Thailand. Scientists stressed it is not clear whether the vaccine would work against other strains in the United States, Africa or elsewhere.

The study tested a two-vaccine combination where the first injection primes the immune system to attack HIV and the second strengthens the response.

The vaccines are ALVAC, from Sanofi Pasteur, the vaccine division of French drugmaker Sanofi-Aventis; and AIDSVAX, originally developed by VaxGen Inc. and now held by Global Solutions for Infectious Diseases, a non-profit founded by some former VaxGen employees.

All the participants tested negative at the start of the trial and were given condoms, counselling and treatment for any sexually transmitted infections. They were tested every six months for HIV and any who became infected were given free treatment with antiviral medicines.

Participants were followed for three years after vaccination ended.

The results were that new infections occurred in 51 of the 8,197 given vaccine and in 74 of the 8,198 who received dummy shots. That worked out to a 31 per cent lower risk of infection for the vaccine group.

The vaccine had no effect on levels of HIV in the blood of those who did become infected, providing "one of the most important and intriguing findings" of the trial, according to Dr Fauci, giving scientists important clues in identifying whether treatment drugs actually make a difference by giving protection to the immune system.

The researchers have been careful to say the vaccine combination appears to have an effect on the HIV strain circulating in Thailand and it may not work on other strains elsewhere in the world.

Full details of the $105 million study will be given at a vaccine conference in Paris in October.

A HIV-blocking gel for women -Breakthrough

Contact: Lee Siegel
leesiegel@ucomm.utah.edu
801-581-8993
University of Utah

New 'molecular condom' meant to prevent AIDS

		IMAGE: University of Utah bioengineer Patrick Kiser analyzes polymers used to develop a new kind of AIDS-preventing vaginal gel for eventual use by women in Africa and other impoverished areas. The... Click here for more information.

SALT LAKE CITY, Aug. 10, 2009 – University of Utah scientists developed a new kind of "molecular condom" to protect women from AIDS in Africa and other impoverished areas. Before sex, women would insert a vaginal gel that turns semisolid in the presence of semen, trapping AIDS virus particles in a microscopic mesh so they can't infect vaginal cells.

"The first step in the complicated process of HIV (human immunodeficiency virus) infection in a woman is the virus diffusing from semen to vaginal tissue. We want to stop that first step," says Patrick Kiser, an associate professor of bioengineering at the University of Utah's College of Engineering. "We have created the first vaginal gel designed to prevent movement of the AIDS virus. This is unique. There's nothing like it."

"We did it to develop technologies that can enable women to protect themselves against HIV without approval of their partner," he adds. "This is important – particularly in resource-poor areas of the world like sub-Sahara Africa and south Asia where, in some age groups, as many as 60 percent of women already are infected with HIV. In these places, women often are not empowered to force their partners to wear a condom."

A study testing the behavior of the new gel and showing how it traps AIDS-causing HIV particles will be published online later this week in the journal Advanced Functional Materials. Kiser is the senior author.

"Due to cultural and socioeconomic factors, women often are unable to negotiate the use of protection with their partner," says Julie Jay, the study's first author and a University of Utah doctoral candidate in pharmaceutics and pharmaceutical chemistry.

So the researchers developed a vaginal gel that a woman could insert a few hours before sex and "could detect the presence of semen and provide a protective barrier between the vaginal tissue and HIV," Jay says. "We wanted to build a gel that would stop HIV from interacting with vaginal tissue."

Kiser estimates that if all goes well, human tests of the gel would start in three to five years, and the gel would reach the market in several more years. He and Jay want to incorporate an antiviral drug into the gel so it both blocks HIV movement and prevents the virus from replicating.

A Rocky Road to Microbicides against AIDS

The effort to develop microbicides – intravaginal gels, rings and films – to prevent transmission of the AIDS virus has been halting. The few that have reached human clinical trials in Africa failed to prevent HIV transmission – either because they carried antiviral drugs that were not long-lived or strong enough, or because patients failed to use them. Some experimental microbicides increased the risk, possibly by irritating vaginal tissue and attracting immune cells that are targeted by the virus.

In 2006, Kiser and colleagues published a study on their development of another "molecular condom" to be applied vaginally as a liquid, turn into a gel coating at body temperature, then, in the presence of semen, turn liquid and release an anti-HIV drug.

Unfortunately, few antiviral drugs bind to and attack HIV in semen. And in Africa, high air temperatures prevent the gel from turning liquid so it could coat the vagina evenly, Kiser says.

The new "molecular condom" gel in the current study works in the opposite way. Like the old version, it changes in response to changes in pH – acidity or alkalinity – in the vagina caused by the introduction of semen during sex. But unlike the old gel, which became liquid at the higher (less acidic) pH of semen, the new "molecular condom" becomes a semisolid at the pH of semen, forming a mesh of "crosslinked" molecules.

The new gel is applied as a gel, and then becomes more solid and impenetrable as changes in pH alter the strength of the bond between the gel's two key components, both of which are polymers, or long, chain-like molecules made of many smaller, repeating units: PBA, or phenylboronic acid, and SHA, or salicylhydroxamic acid.

Slowing and Blocking the AIDS Virus

Kiser's team first published a study about the invention of the polymers and their behavior in 2007. A patent is pending on the invention.

The chemical bonds between the two polymers constantly attach and detach at normal, acidic vaginal pHs of about 4.8, allowing the gel to flow, Kiser says. But at a pH of 7.6 – the slightly alkaline condition when semen enters the vagina – the PBA and SHA polymers "crosslink" and stick tightly together, he adds.

Part of the new study characterized the flow of the gel.

"It flows at a vaginal pH, and the flow becomes slower and slower as pH increases, and it begins to act more solid at the pH of semen," Jay says. HIV moves slowly within the gel, even when the gel is at lower pHs (higher acidity) and still flowing, but the virus is blocked at higher pHs caused by the entry of semen into the vagina.

The crosslinked polymers form a mesh that is smaller than microscopic, and instead is nanoscopic – on the scale of atoms and molecules – with a mesh size of a mere 30 to 50 nanometers – or 30 to 50 billionths of a meter. (A meter is about 39 inches.)

By comparison, an HIV particle is about 100 nanometers wide, sperm measure about 5 to 10 microns (5,000 to 10,000 nanometers) in cross section, and the width of a human hair is roughly 100 microns (100,000 nanometers).

Kiser says the gel should block other viruses and sperm, thus could work as a contraceptive and possibly prevent infection by herpes viruses and human papillomavirus (HPV), a major cause of cervical cancer.

The gel also could help prevent AIDS by blocking movement of immune system cells that try to combat infectious agents but instead get hijacked by the AIDS virus.

During the study, coauthors from Northwestern University in Chicago used a sophisticated microscope to track how fast HIV particles marked with fluorescent dye moved when they were caught in the gel, and how the speed varied with changes in pH.

The researchers compared movement of HIV particles with latex particles, which revealed that under somewhat acidic conditions, the HIV particles are slowed down in part because their surfaces react chemically with the polymers.

By adding an anti-AIDS drug such as tenofovir to the gel, "the virus would have two barriers to get through: the polymer barrier and then the drug barrier," Kiser says. Unlike an antiviral used with the old gel, tenofovir would not attack HIV directly, but protect immune cells in the vagina from infection.

Kiser says that after sex, the vagina gradually becomes acidic again, and any residual HIV particles would be inactivated both by acidity and an antiviral drug within the remaining gel, which still impedes HIV to some extent at normal vaginal acidity.

Kiser and Jay conducted the study with four other University of Utah researchers: bioengineering undergraduates Kristofer Langheinrich and Melissa Hanson, bioengineering graduate student Todd Johnson, and bioengineering researcher Meredith Clark. Other coauthors were from the Department of Cell and Molecular Biology at Northwestern University Medical School in Chicago: Thomas Hope, Shetha Shukair and Gianguido Cianci.

The study was funded by National Institutes of Health. Kiser's research team is continuing the effort to develop microbicides to prevent AIDS thanks to a $100,000 grant from the Bill and Melinda Gates Foundation.

Upcoming work includes assessing the HIV-prevention potential of other polymers, testing the safety of the new gel on vaginal cells, and studying how well the new gel blocks the transport of HIV into samples of human vaginal and penile tissue from hysterectomies and circumcisions, respectively.

###

University of Utah Public Relations
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Salt Lake City, Utah 84112-9017
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22 porn-film actors got HIV since 2004

Health officials in Los Angeles said Friday that 22 actors in adult-sex movies had contracted HIV since 2004, when a previous outbreak led to efforts to protect employees in California's multibillion-dollar pornography industry.

By GARDINER HARRI

The New York Times

Health officials in Los Angeles said Friday that 22 actors in adult-sex movies had contracted HIV since 2004, when a previous outbreak led to efforts to protect employees in California's multibillion-dollar pornography industry.

The officials accused an industry-supported health clinic of failing to cooperate with state investigations and of failing to protect industry workers and their sexual partners.

"We have an industry that is exposing workers to life-threatening diseases as part of their employment," said Dr. Jonathan Fielding, director of public health for Los Angeles County.

The latest controversy began Thursday, when the Los Angeles Times reported that an adult-film actress had tested positive for the human immunodeficiency virus (HIV), which causes AIDS. The infection was confirmed by the Adult Industry Medical Healthcare Foundation, a clinic founded by a former adult-film actress.

The foundation's Web site states that the actress tested negative for HIV on April 29, but a positive test result was confirmed June 4. The woman performed in a film June 5. A second test came back positive last Saturday.

Co-stars of the woman have tested negative for HIV but have been quarantined from acting for the time being and advised to be retested in two weeks.

Clinic officials refused to comment Friday.

Dean Fryer, a spokesman for the California Division of Occupational Safety and Health, said the clinic "is not cooperative with us."

"We don't even know who the employer is in the most recent case, we don't know who the talent is."

Regulations require filmmakers to provide protection against the transmission of disease, such as condoms or using film techniques that involve simulations. "There is no reason these infections should be occurring if these employers are following these precautions," Fryer said.

The pornographic-film industry is centered in the San Fernando Valley, northwest of downtown Los Angeles. An estimated 200 production companies in the region employ up to 1,500 performers, making up to 11,000 films and earning as much as $13 billion a year.

Some health advocates have pressed for legislation requiring condom use in sex scenes.

Steven Hirsch, chief executive of the sex-movie company Vivid Entertainment, said condoms were optional among its actors. "Performers have the right to choose to use or not use condoms. They're adults, they know what industry they're in."

Material from The Associated Press is included in this report.

Copyright © 2009 The Seattle Times Company

Modified tobacco plant may block HIV

OWENSBORO, Ky., March 31 (UPI) -- A gel derived from a close relative to the tobacco plant is being tested as an affordable preventative measure for HIV, U.S. researchers said.

Kenneth Palmer, a senior scientist in the University of Louisville's Owensboro Cancer Research Program, has published research that suggests growing large quantities of the protein griffithsin found in the transgenic plant Nicotiana benthamiana can prevent human immunodeficiency virus from infecting cells of the immune system, the university's James Graham Brown Cancer Center said in a release.

Palmer said the drug could be manufactured in the form of a microbicide gel or film for topical application, with a selling price comparable to condoms.

They modified the tobacco mosaic virus to incorporate the griffithsin gene and infected more than 9,300 tobacco plants. Scientists were able to extract enough griffithsin to produce about 100,000 HIV microbicide doses from the leaves. The chemical performed identically to griffithsin produced by other methods, the report said.

On Africa trip, pope says condoms won't solve AIDS

By VICTOR L. SIMPSON, Associated Press Writer

Play Video AP – Pope says condoms won't solve AIDS

YAOUNDE, Cameroon – Pope Benedict XVI said condoms are not the answer to the AIDS epidemic in Africa and can make the problem worse, setting off criticism Tuesday as he began a weeklong trip to the continent where some 22 million people are living with HIV.

Benedict's first statement on an issue that has divided even Catholic clergy working with AIDS patients came hours before he arrived in Cameroon's capital — greeted by thousands of flag-waving faithful who stood shoulder-to-shoulder in red dirt fields and jammed downtown streets for a glimpse of the pontiff's motorcade.

In his four years as pope, Benedict had never directly addressed condom use, although his position is not new. His predecessor, Pope John Paul II, often said that sexual abstinence — not condoms — was the best way to prevent the spread of the disease.

Benedict also said the Roman Catholic Church was at the forefront of the battle against AIDS.

"You can't resolve it with the distribution of condoms," the pope told reporters aboard the Alitalia plane heading to Yaounde. "On the contrary, it increases the problem."

The pope said a responsible and moral attitude toward sex would help fight the disease, as he answered questions submitted in advance by reporters traveling on the plane. His response was presumably also prepared in advance.

The Catholic Church rejects the use of condoms as part of its overall teaching against artificial contraception. Senior Vatican officials have advocated fidelity in marriage and abstinence from premarital sex as key weapons in the fight against AIDS.

AP – Pope Benedict XVI waves to a cheering crowd as he leaves the airport in Yaounde, Cameroon Tuesday, March …

The late Cardinal Alfonso Lopez Trujillo made headlines in 2003 for saying that condoms may help spread AIDS through a false sense of security, claiming they weren't effective in blocking transmission of the virus. The cardinal, who died last year, headed the Vatican's Pontifical Council for the Family.

Three-quarters of all AIDS deaths worldwide in 2007 were in sub-Saharan Africa, where some 22 million people are infected with HIV — accounting for two-thirds of the world's infections, according to UNAIDS.

Rebecca Hodes with the Treatment Action Campaign in South Africa said if the pope is serious about preventing HIV infections, he should focus on promoting wide access to condoms and spreading information on how to use them.

"Instead, his opposition to condoms conveys that religious dogma is more important to him than the lives of Africans," said Hodes, head of policy, communication and research for the group.

Hodes said the pope was right that condoms are not the sole solution to Africa's AIDS epidemic, but added they are one of the very few proven measures to prevent HIV infections.

Even some priests and nuns working with those infected with the AIDS virus question the church's opposition to condoms amid the pandemic ravaging Africa. Ordinary Africans do as well.

"Talking about the nonuse of condoms is out of place. We need condoms to protect ourselves against diseases and AIDS," teacher Narcisse Takou said in Yaounde.

Stanley Obale Okpu, a civil servant working in the ministry of urban development in Cameroon, said: "What the pope says is an ideal for the Catholic church. But he needs to look at the realities on the ground. One should be aware of these realities. In the case of Cameroon — and Africa as a whole — condoms are very necessary ... You need condoms to prevent AIDS and birth control."

A crowd of photographers and cameras flashed as the 81-year-old pontiff stepped off the plane into the steaming 88-degree heat, with humidity levels measuring a wilting 90 percent.

It was the first stop on a weeklong pilgrimage that will also take Benedict to Angola as he seeks to draw international attention to Africa's problems of famine, poverty and armed conflict.

The pope was greeted by Cameroon's President Paul Biya, who has ruled since 1982 and whose government has been accused by Amnesty International of abuses in crushing political opponents.

The pope made no specific reference to the situation in Cameroon, but he did say in general remarks on Africa that "a Christian can never remain silent" in the face of violence, poverty, hunger, corruption or abuse of power.

"The saving message of the Gospel needs to be proclaimed loud and clear so that the light of Christ can shine into the darkness of people's lives," Benedict said as the president and other political leaders looked on.

Africa is the fastest-growing region for the Catholic church, though it competes with Islam and evangelical churches.

The pope said Tuesday he intends to make an appeal for "international solidarity" for Africa in the face of the global economic downturn. He said while the church does not propose specific economic solutions, it can give "spiritual and moral" suggestions.

He described the current crisis as the result of "a deficit of ethics in economic structures."

"It is here that the church can make a contribution," he said.

On the plane, Benedict also dismissed the notion that he was facing increasing opposition and isolation within the church, particularly after an outreach to ultraconservatives that led to his lifting the excommunication of a Holocaust-denying bishop.

"The myth of my solitude makes me laugh," the pope said, adding that he has a network of friends and aides whom he sees every day.

___

Associated Press writers Krista Larson in Johannesburg and Emmanuel Tumanjong in Yaounde contributed to this report.

Man appears free of HIV after stem cell transplant

By Jacquelyne Froeber

A 42-year-old HIV patient with leukemia appears to have no detectable HIV in his blood and no symptoms after a stem cell transplant from a donor carrying a gene mutation that confers natural resistance to the virus that causes AIDS, according to a report published Wednesday in the New England Journal of Medicine.

The patient underwent a stem cell transplant and since, has not tested positive for HIV in his blood.

"The patient is fine," said Dr. Gero Hutter of Charite Universitatsmedizin Berlin in Germany. "Today, two years after his transplantation, he is still without any signs of HIV disease and without antiretroviral medication."

The case was first reported in November, and the new report is the first official publication of the case in a medical journal. Hutter and a team of medical professionals performed the stem cell transplant on the patient, an American living in Germany, to treat the man's leukemia, not the HIV itself.

However, the team deliberately chose a compatible donor who has a naturally occurring gene mutation that confers resistance to HIV. The mutation cripples a receptor known as CCR5, which is normally found on the surface of T cells, the type of immune system cells attacked by HIV.

The mutation is known as CCR5 delta32 and is found in 1 percent to 3 percent of white populations of European descent.

HIV uses the CCR5 as a co-receptor (in addition to CD4 receptors) to latch on to and ultimately destroy immune system cells. Since the virus can't gain a foothold on cells that lack CCR5, people who have the mutation have natural protection. (There are other, less common HIV strains that use different co-receptors.)

People who inherit one copy of CCR5 delta32 take longer to get sick or develop AIDS if infected with HIV. People with two copies (one from each parent) may not become infected at all. The stem cell donor had two copies.

While promising, the treatment is unlikely to help the vast majority of people infected with HIV, said Dr. Jay Levy, a professor at the University of California San Francisco, who wrote an editorial accompanying the study. A stem cell transplant is too extreme and too dangerous to be used as a routine treatment, he said.

"About a third of the people die [during such transplants], so it's just too much of a risk," Levy said. To perform a stem cell transplant, doctors intentionally destroy a patient's immune system, leaving the patient vulnerable to infection, and then reintroduce a donor's stem cells (which are from either bone marrow or blood) in an effort to establish a new, healthy immune system.

Levy also said it's unlikely that the transplant truly cured the patient in this study. HIV can infect many other types of cells and may be hiding out in the patient's body to resurface at a later time, he said.

"This type of virus can infect macrophages (another type of white blood cell that expresses CCR5) and other cells, like the brain cells, and it could live a lifetime. But if it can't spread, you never see it-- but it's there and it could do some damage," he said. "It's not the kind of approach that you could say, 'I've cured you.' I've eliminated the virus from your body." Health.com: 10 questions to ask a new partner before having sex

Before undergoing the transplant, the patient was also found to be infected with low levels of a type of HIV known as X4, which does not use the CCR5 receptor to infect cells. So it would seem that this virus would still be able to grow and damage immune cells in his body. However, following the transplant, signs of leukemia and HIV were absent.

"There is no really conclusive explanation why we didn't observe any rebound of HIV," Hutter said. "This finding is very surprising."

Hutter noted that one year ago, the patient had a relapse of leukemia and a second transplant from the same donor. The patient experienced complications from the procedure, including temporary liver problems and kidney failure, but they were not unusual and may occur in HIV-negative patients, he said.

Researchers including Hutter agree that the technique should not be used to treat HIV alone. "Some people may say, 'I want to do it,'" said Levy. A more logical -- and potentially safer -- approach would be to develop some type of CCR5-disabling gene therapy or treatment that could be directly injected into the body, said Levy.

Less invasive options to alter CCR5 could be on the horizon within the next five years, said Levy. "It's definitely the wave of the future," he said. "As we continue to follow this one patient, we will learn a lot."

One drug that's currently on the market that blocks CCR5 is called maraviroc (Selzentry). It was first approved in 2007 and is used in combination with other antiretroviral drugs. Health.com: Who's most at risk for STDs?

In 2007, an estimated 2 million people died from AIDS, and 2.7 million people contracted HIV. More than 15 million women are infected worldwide. HIV/AIDS can be transmitted through sexual intercourse, sharing needles, pregnancy, breast-feeding, and/or blood transfusions with an infected person. Health.com:What should I do if the condom breaks?

"For HIV patients, this report is an important flicker of hope that antiretroviral therapy like HAART [highly active antiretroviral therapy] is not the endpoint of medical research," Hutter said.

Drugs Are Found to Block HIV In Monkeys

The Truvada pill, made by Gilead Sciences, contains two antiretroviral drugs and was tested on monkeys in a scientific study. (By Paul Sakuma -- Associated Press)

Pills, Gel May Help Protect Women

By David Brown
Washington Post Staff Writer
Tuesday, February 10, 2009; A02

AIDS researchers who were gathered in Montreal yesterday heard encouraging results from studies of three strategies for preventing HIV infection using pharmaceuticals, particularly in women.

Two experiments in monkeys showed that antiretroviral (ARV) drugs, given by mouth or by vaginal gel, were highly effective in blocking infection by the virus that causes AIDS.

A third study, in 3,100 women in the United States and Africa, showed a small amount of protection from a vaginal gel that acts by binding up the AIDS virus and preventing it from invading cells.

Many experts believe that, short of a vaccine, a virus-blocking substance that could be inserted in the vagina or rectum before sexual activity would be the most important tool in fighting the AIDS pandemic. Numerous topical microbicides have been tried, but none have worked, and two have actually increased the risk of infection.

"The field of microbicide gels is now moving into a new generation," said Walid Heneine, a virologist at the U.S. Centers for Disease Control and Prevention, who led one of the monkey studies.

Microbicides can be applied without the knowledge of sexual partners. They are seen as being especially important in cultures where the subservient status of women makes it difficult for them to insist on abstinence or condom use, the two proven methods of preventing infection through sexual contact. In sub-Saharan Africa, nearly 60 percent of HIV-positive people are women.

The gel used in the human study reduced the risk of infection by 30 percent over the course of about two years, an effect that did not reach the level of statistical significance. The women -- from the United States, South Africa, Malawi, Zambia and Zimbabwe -- also used condoms in about three-quarters of their sexual encounters.

A study by British and African researchers that is testing the same microbicide in 9,400 women may have interim results later this year.

Although this result was marginal, the substance, called PRO 2000/5, may ultimately prove useful to women who are monogamous, are married to high-risk men and do not want to use condoms because they want to conceive, the lead researcher said.

"This could be a niche product for a group of women who have no other option," said Salim Abdool Karim of Durban, South Africa. He spoke at a news conference at the 16th Conference on Retroviruses and Opportunistic Infections, the annual mid-winter AIDS meeting in North America.

In the first monkey study, researchers gave rhesus macaques oral doses of a compound containing two ARV drugs, tenofovir and emtricitabine (which is sold under the name Truvada). The medicine was administered at different intervals, both before and after the animals were rectally exposed to the AIDS virus once a week for three months.

When the first dose was given either one or three days before contact with the virus, five out of six animals were protected. When it was given seven days before exposure, four in six animals were protected. When the dose was two hours before exposure, however, only three in six were protected.

Of 27 untreated animals, 26 became infected after an average of two exposures.

Tenofovir has a very long active life inside the body. But two hours appears to be not enough time for it to be absorbed and carried into the cells of the immune system, which are HIV's target, said J. Gerardo García-Lerma, the CDC virologist who led the study.

There are seven studies in people testing either Truvada or tenofovir alone as an HIV-prevention pill. In each of the experiments, which are enrolling a total of 18,000 volunteers in the United States, Kenya, Uganda, Botswana and Thailand, the drugs are administered every day. The monkey study suggests that intermittent dosing might work, too.

In the other monkey study, researchers used vaginal gels containing either both drugs or tenofovir alone. The gel was applied half an hour before twice-weekly vaginal exposure to the virus.

The six monkeys that received the two-drug gel were all protected, as were the six who got the tenofovir-only gel. Of 11 monkeys in a control group, 10 became infected after an average of four exposures to the virus.

Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, said he was buoyed by the results of the animal experiments and not entirely discouraged by the human results.

"In such a sea of disappointment as microbicide research, a study that is even a little encouraging is something to notice," he said.