HIV Vaccine Ready for Human Tests

An HIV/AIDS vaccine developed in Canada has passed safety tests in animals and the researchers are awaiting approval to begin human trials in the U.S.

"It is a very important milestone for us," said Yong Kang, a professor of microbiology at the University of Western Ontario in London who has been working on the vaccine for 20 years.

Kang said he expects to get the go-ahead soon from the U.S. Food and Drug Administration to begin human toxicology tests and two phases of clinical trials in the United States.

If all three trials are successful, the vaccine should be available within the next decade, Kang told CBC News on the phone while attending a meeting in South Korea.

According to a 2008 United Nations report on the global AIDS epidemic, 33 million people were living with HIV in 2007. Two million people died of causes related to the disease that year.

Dozens of HIV vaccines have already been developed and tested in animal models, but few have been tested in humans, none successfully. A promising trial in 2007 by pharmaceutical giant Merck and Co. was shut down after those receiving the vaccine contracted HIV at a higher rate than those who received the placebo.

Kang has partnered with a Curacom, a South Korean holding company, that has agreed to open an office in London, Ont., to help fund research in Kang's lab and commercialize the vaccine.

A test vaccine is being manufactured in a lab in Maryland near Washington, D.C.

Lab tests showed the vaccine produced no adverse effects or safety risks during immunology tests on animals.

The toxicology tests are expected to include 40 to 50 HIV-positive volunteers in the U.S., and will be designed to test whether the vaccine is toxic in humans.

http://www.cbc.ca/health/story/2009/07/01/health-canadian-aids-hiv-vaccine-kang.html

Antibodies Present in Long-Term HIV Survivors Could Contribute to Vaccine Development

HIV-positive people who do not develop AIDS and do not require antiretroviral medication could provide insight for new strategies in vaccine development, according to a study published Sunday in the journal Nature, London's Independent reports. Michel Nussenzweig -- head of Rockefeller University's Laboratory of Molecular Immunology and author of the study -- said his research aimed to harness natural mechanisms to target HIV rather than use synthetically produced antibodies, some of which have failed in earlier HIV vaccine trials.

For the study, Rockefeller University researchers examined antibodies present in the blood of six long-term HIV survivors who appeared to have a degree of natural immunity to the virus (Connor, Independent, 3/16). The researchers isolated 433 antibodies from the patients, all of which targeted HIV's protective outer coating, or "envelope." The researchers then cloned the antibodies and observed which elements of the envelope each antibody targeted and how effectively it neutralized HIV. During the research, Johannes Scheid, a doctoral student at Rockefeller University, identified a new structure on the HIV envelope that scientists previously had not recognized as an antibody target. Although the researchers determined that each antibody individually had a weak effect on HIV, they also found that the antibodies as a group effectively targeted the virus (PA/Google.com, 3/15). In addition, the researchers determined that a prototype vaccine developed from several of the antibodies can prevent the growth of HIV in human cells in a test tube.

Nussenzweig said the study identified "many different antibodies that individually have limited neutralizing ability but together are quite powerful." According to Nussenzweig, only about one in every 1,000 HIV-positive people produces the neutralizing antibodies. He said the research attempts a new approach to HIV vaccine development by "copying what exists in nature and that we know can work because of the long-term survivors." He added, "Instead of inventing something that doesn't exist, it's trying to copy something that does exist." Nussenzweig said the study's results "should make people think about what an effective vaccine should look like." According to the Independent, the researchers next plan to conduct further trials of vaccine candidates on laboratory animals and human volunteers.

The Independent also profiled Kai Brothers, a San Francisco man who has been living with HIV for 28 years without developing AIDS or requiring antiretroviral medications. The Independent reports that Brothers, who did not participate in the new study, might be one of "a few -- perhaps as few as one in 5,000" -- HIV-positive people who have natural immunity to the virus. Brothers said he has participated in HIV research for 10 years, adding, "I feel dedicated to giving back something because of my good fortune" (Independent, 3/16).

An abstract of the study is available online.

Microbicide Containing Natural Compound Provides Protection in Monkeys Against Simian Version of HIV

An experimental microbicide containing a naturally occurring compound provides protection in monkeys against the simian version of HIV by diminishing immune responses to the virus, according to a study published Wednesday in the journal Nature, the Los Angeles Times reports. HIV typically spreads in the body by entering CD4+ T cells, which the immune system sends out to attack the virus after exposure. The compound -- called glycerol monolaurate, or GML -- works by inhibiting immune signals that dispatch the T cells to attack the infection. It is those T cells that HIV infects and uses to proliferate throughout the body (Engel, Los Angeles Times, 3/5). GML occurs naturally in the human body and already is approved for use as an antimicrobial and anti-inflammatory ingredient in cosmetics and toiletries, as well as an emulsifier in foods. In addition, each dose of GML used in the study costs less than one cent. According to the researchers, the study's findings have promising implications for the development of effective microbicides to prevent HIV (AFP/Google.com, 3/4).

For the study -- led by Ashley Haase, head of the microbiology department at the University of Minnesota Medical School, and microbiologist Patrick Schlievert -- researchers administered the GML gel vaginally to five rhesus monkeys and then repeatedly exposed them to the simian version of HIV, or SIV. After two weeks, all of the five monkeys tested negative for the virus. However, four out of five monkeys that did not receive the GML gel contracted SIV. According to the researchers, five months after the experiment, they learned that one of the monkeys treated with GML tested positive for the virus. The researchers said they are unsure how this monkey contracted SIV, but they suggested that a small amount of the virus might have spread in the body undetected or the monkey might have been exposed to SIV after the study ended (Lerner, Minneapolis Star Tribune , 3/4).

Haase said the current research is "a relatively preliminary study but worth sharing because it establishes a novel approach." The researchers added that a mathematical model suggests that even if the microbicide were 60% effective and used 20% of the time, it still could prevent about 2.3 million HIV cases over a three-year period. According to the study authors, researchers will need to conduct further animal studies to determine whether the microbicide should be administered over a longer period of time to provide long-term protection against the virus (Los Angeles Times, 3/5). Further study also will be needed to demonstrate whether GML prevents HIV transmission among humans, they added. The researchers said they plan to undertake a larger study with monkeys, followed by a study with female volunteers. In addition, the University of Minnesota has applied for patents for the new compound combining GML with a personal lubricant, which currently is not available commercially. According to Schlievert, the ultimate goal will be to develop a gel that can be used for both men and women (Minneapolis Star Tribune, 3/4).

According to the study authors, the research "represents a highly encouraging new lead in the search for an effective microbicide to prevent HIV transmission that meets the criteria of safety, affordability and efficacy" (Fox, Reuters, 3/4). Haase said that although the research "sounds counter-intuitive, halting the body's natural defense system might actually prevent transmission and rapid spread of the infection" (AFP/Google.com, 3/4). Charlene Dezzutti, laboratory network director of the Microbicides Trial Network at the University of Pittsburgh, said the research illustrates "a new approach to thinking about microbicides." She added that she believes scientists "definitely" could develop an effective microbicide before developing an HIV/AIDS vaccine. "It's just a matter of getting all the right pieces together," she said (Lauerman, Bloomberg, 3/4). Rowena Johnston, vice president of research for the Foundation for AIDS Research, said that if further studies confirm these results, "then this is really a fabulous new finding." She said that although future microbicide research could encounter setbacks, the study is "absolutely a great beginning to a research project."

According to Schlievert, women could apply the GML microbicide "an hour or so before they had sex" to protect against HIV transmission. In addition, the gel might provide protection against other sexually transmitted infections, such as chlamydia, he said (Minneapolis Star Tribune, 3/4). According to AFP/Google.com, Schlievert first identified the microbicidal properties of GML when studying the use of the compound in preventing toxic shock syndrome associated with tampons. He said research repeatedly has found that the compound is safe and has no effect on beneficial vaginal bacteria (AFP/Google.com, 3/4). Lorraine Teel, executive director of the Minnesota AIDS Project, said the gel could provide women with a way to prevent disease transmission in areas of the world where many people do not use condoms because of cultural or other pressures. The research has "absolutely enormous implications" for women worldwide, she said (Minneapolis Star Tribune, 3/4). Anthony Fauci, director of NIH's National Institute of Allergy and Infectious Diseases, said an effective microbicide would "empower women to protect themselves in a sexual situation in which they may not have complete control" (Los Angeles Times, 3/5).

An abstract of the study is available online.

AIDS Vaccine

Merck's Experimental AIDS Vaccine Fails

By LINDA A. JOHNSON – Sep 22, 2007

TRENTON, N.J. (AP) — In a disappointing setback, a promising experimental AIDS vaccine failed to work in a large international test, leading the developer to halt the study. Merck & Co. said Friday that it is ending enrollment and vaccination of volunteers in the study, which was partly funded by the National Institutes of Health.

It was a high-profile failure in the daunting quest to develop a vaccine to prevent AIDS. Merck's vaccine was the farthest along and was closely watched by experts in the field.

Officials at the company, based in Whitehouse Station, N.J., said 24 of 741 volunteers who got the vaccine in one segment of the experiment later became infected with HIV, the virus that causes AIDS. In a comparison group of volunteers who got dummy shots, 21 of 762 participants also became infected.

"It's very disappointing news," said Keith Gottesdiener, head of Merck's clinical infectious disease and vaccine research group. "A major effort to develop a vaccine for HIV really did not deliver on the promise."

Michael Zwick, an HIV researcher at Scripps Research Institute, said the vaccine's failure is unfortunate. But he said it's too soon to know if other vaccines using the same strategy would also fail.

"It's par for the course in the HIV field," he said of the Merck result.

The volunteers in the experiment were all free of HIV at the start. But they were at high risk for getting the virus: Most were homosexual men or female sex workers. They were all repeatedly counseled about how to reduce their risk of HIV infections, including use of condoms, according to Merck.

In a statement, the NIH said a data safety monitoring board, reviewing interim results, found the vaccine did not prevent HIV infection. Nor did it limit severity of the disease "in those who become infected with HIV as a result of their own behaviors that exposed them to the virus" — another goal of the study.

Merck's was the first major test of a new strategy to prevent HIV infection. The first wave of attempts to develop a vaccine tried to stimulate antibodies against the virus, but that hasn't worked so far.

The new effort — an approach that Gottesdiener said is being tried in most other current research — is aimed at making the body produce more of a crucial immune cell called killer T cells. The goal is to simultaneously "train" those cells, like an army, to quickly recognize and destroy the AIDS virus when it enters cells in the bloodstream.

Zwick said some researchers still are working on vaccines to neutralize the AIDS virus. He thinks ultimately what's needed is one that combines that approach with a way to stimulate and train killer T cells.

Merck and the HIV Vaccine Trials Network, an international collaboration of researchers and institutions funded by the NIH, co-sponsored the study. The experiment, called STEP, began in December 2004 and had enrolled 3,000 volunteers in Australia, Brazil, Canada, the Dominican Republic, Haiti, Jamaica, Peru, Puerto Rico and the United States.

The results announced Friday involved volunteers who researchers thought would benefit most because they had never been exposed to the particular cold virus used in the vaccine.

Wall Street, on a generally upbeat day, showed little reaction to the news, with Merck shares rising 44 cents to $51.82.

Analyst Steve Brozak of WBB Securities said the vaccine was considered the most promising candidate both by Wall Street and the science community. He said a vaccine is the only financially feasible way to fight the AIDS epidemic in poor countries and that the company that comes up with the first successful shot would have "a license to print money."

"You're talking about a Carl Sagan kind of number — billions and billions" of dollars, he said.

The Merck vaccine, known only as V520, also was being tested in a similar study in South Africa and in two smaller studies, which also were halted.

The Merck vaccine failure is a "deep disappointment and a scientific setback for the AIDS vaccine field," the AIDS Vaccine Advocacy Coalition said in a statement. However, the nonprofit group added that "while this is a disappointment, it is in no way the end of the search for an AIDS vaccine."

((Considering that the vaccine has failed, there are still several viable and inexpensive treatment options available at AIDS Drugs Online))

AIDS Vaccine

Merck's Experimental AIDS Vaccine Fails

By LINDA A. JOHNSON – Sep 22, 2007

TRENTON, N.J. (AP) — In a disappointing setback, a promising experimental AIDS vaccine failed to work in a large international test, leading the developer to halt the study. Merck & Co. said Friday that it is ending enrollment and vaccination of volunteers in the study, which was partly funded by the National Institutes of Health.

It was a high-profile failure in the daunting quest to develop a vaccine to prevent AIDS. Merck's vaccine was the farthest along and was closely watched by experts in the field.

Officials at the company, based in Whitehouse Station, N.J., said 24 of 741 volunteers who got the vaccine in one segment of the experiment later became infected with HIV, the virus that causes AIDS. In a comparison group of volunteers who got dummy shots, 21 of 762 participants also became infected.

"It's very disappointing news," said Keith Gottesdiener, head of Merck's clinical infectious disease and vaccine research group. "A major effort to develop a vaccine for HIV really did not deliver on the promise."

Michael Zwick, an HIV researcher at Scripps Research Institute, said the vaccine's failure is unfortunate. But he said it's too soon to know if other vaccines using the same strategy would also fail.

"It's par for the course in the HIV field," he said of the Merck result.

The volunteers in the experiment were all free of HIV at the start. But they were at high risk for getting the virus: Most were homosexual men or female sex workers. They were all repeatedly counseled about how to reduce their risk of HIV infections, including use of condoms, according to Merck.

In a statement, the NIH said a data safety monitoring board, reviewing interim results, found the vaccine did not prevent HIV infection. Nor did it limit severity of the disease "in those who become infected with HIV as a result of their own behaviors that exposed them to the virus" — another goal of the study.

Merck's was the first major test of a new strategy to prevent HIV infection. The first wave of attempts to develop a vaccine tried to stimulate antibodies against the virus, but that hasn't worked so far.

The new effort — an approach that Gottesdiener said is being tried in most other current research — is aimed at making the body produce more of a crucial immune cell called killer T cells. The goal is to simultaneously "train" those cells, like an army, to quickly recognize and destroy the AIDS virus when it enters cells in the bloodstream.

Zwick said some researchers still are working on vaccines to neutralize the AIDS virus. He thinks ultimately what's needed is one that combines that approach with a way to stimulate and train killer T cells.

Merck and the HIV Vaccine Trials Network, an international collaboration of researchers and institutions funded by the NIH, co-sponsored the study. The experiment, called STEP, began in December 2004 and had enrolled 3,000 volunteers in Australia, Brazil, Canada, the Dominican Republic, Haiti, Jamaica, Peru, Puerto Rico and the United States.

The results announced Friday involved volunteers who researchers thought would benefit most because they had never been exposed to the particular cold virus used in the vaccine.

Wall Street, on a generally upbeat day, showed little reaction to the news, with Merck shares rising 44 cents to $51.82.

Analyst Steve Brozak of WBB Securities said the vaccine was considered the most promising candidate both by Wall Street and the science community. He said a vaccine is the only financially feasible way to fight the AIDS epidemic in poor countries and that the company that comes up with the first successful shot would have "a license to print money."

"You're talking about a Carl Sagan kind of number — billions and billions" of dollars, he said.

The Merck vaccine, known only as V520, also was being tested in a similar study in South Africa and in two smaller studies, which also were halted.

The Merck vaccine failure is a "deep disappointment and a scientific setback for the AIDS vaccine field," the AIDS Vaccine Advocacy Coalition said in a statement. However, the nonprofit group added that "while this is a disappointment, it is in no way the end of the search for an AIDS vaccine."

((Considering that the vaccine has failed, there are still several viable and inexpensive treatment options available at www.aids-drugs-online.com))

Cipla launches 3-in-1 AIDS drug in India

Cipla has launched an innovative combination of 3 HIV/AIDS drugs, Viraday that needs to be taken just once a day for effective treatment.

The three anti-HIV drugs efavirenz 600 mg, tenofovir 300 mg and emtricitabine 200mg comprise the drug Viraday. Viraday, one tablet of which alone effectively treats a HIV infected person, eliminates the need for 3 separate medicines. This drug has some advantages like, it is less burdensome and it can be taken along with tuberculosis medicines, which could not be done previously.

This combination drug, that was previously available only in the U.S. and European countries, was first launched in India by Cipla on Thursday. In the U.S. and Europe this combination drug costs Rs. 52,800 a month, whereas Cipla will make it accessible at just Rs. 5,200 per month. This combination drug is less toxic than when the drugs are taken separately.

This breakthrough would improve the adherence-how faithfully patients stick to the course of treatment advised by the doctor. “This is a vital issue in HIV treatment to prevent the infection from reaching the advanced stage of AIDS,” said senior consultant in Internal Medicine at Indraprastha Apollo Hospital, Dr Nalin Nag. He said, “Viraday is very patient friendly, as it requires just one pill a day and freedom from the severe side effect of many other anti HIV drugs.”

The innovative treatment kits and the 3-in-1 pills introduced by Cipla will promote adherence and ease of use. Viraday is the most remarkable accomplishment of Cipla.

Cipla has brought down the price of HIV/AIDS drugs in international market. It supplies HIV/AIDS drugs to majority of African, South Asian, Latin American and several other developing countries.

Source-Medindia
GYT

Find Viraday available at www.aids-drugs-online.com

HIV Funding announcement

Lewis confident in HIV vaccine funding announcement

Billionaire philanthropist Bill Gates and Prime Minister Stephen Harper are expected to announce joint financing plans on Tuesday to test a possible vaccine for HIV.

It is expected that the vaccine funding announcement will be made in Ottawa when Gates visits the Canadian Chamber of Commerce.

'This is an important step forward.'—Former UN Envoy for HIV/AIDS Stephen Lewis on expected HIV vaccine funding announcement

"Gates doesn't put a significant amount of money into vaccine research unless he's absolutely certain that it might yield something down the road," Stephen Lewis, the former UN secretary-general's special envoy for HIV/AIDS in Africa, told CBC Newsworld on Monday.

"They are scrupulous, the Bill Gates Foundation, in their assessment of what will work and what will not work. So this is an important step forward, and I honour the government of Canada for being a part of it."

Both the previous Liberal government and the current Conservative government have helped to fund the International AIDS Vaccine Initiative.

In an exclusive interview with Peter Mansbridge, chief correspondent of CBC News, Gates said he also anticipates a vaccine for HIV in his lifetime.

"This money is going to be spent on some very important causes in this century, and of the top 20 diseases that create the inequity, we will have either had drugs or vaccines to virtually eliminate most all of those," Gates said on Feb. 9. "AIDS is the toughest, but certainly in my lifetime, I'd be very surprised if we don't have a vaccine."

Tuesday's appearance will be another chance for the Prime Minister to address the AIDS issue. Last summer, Harper was criticized for not attending the International AIDS Conference in Toronto, where frontline workers, heads of state and scientists talked about issues including the search for a vaccine, the stigma around HIV and AIDS and circumcision as a form of prevention.

There was speculation that Harper would use the conference to announce new AIDS funding, but he said it wouldn't be the right time to make announcements because the issue had become "so politicized" during the week. Three cabinet ministers, including Health Minister Tony Clement attended the conference, along with Gov. Gen. Michaëlle Jean.

The federal government has yet to demonstrate that it is willing to fight HIV on other fronts, such as funding the developing of an anti-retroviral drug to export to developing countries — an idea that has been on the books for four years, Lewis said.

It is important to fund all aspects of research: from antiretroviral treatment to keep people alive, to the search for microbicides to help protect women, to a vaccine, he added.

Microbicide setback

In one area of research hoped fight HIV/AIDS, scientists are developing vaginal microbicides, which are aimed at preventing sexual transmission of HIV and other sexually transmitted infections when applied topically. Scientists hope that women could be encouraged to apply them without their partner's knowledge, to reduce the risk of infection when men refuse to wear condoms.

However, in January, researchers halted studies in Africa and India of a microbicide developed in Canada after women using the gel showed a higher risk of infection rather than lower.

A microbicide likely won't be available for use for at least five years, and a vaccine 10 years, Lewis said, because HIV is so artful at outwitting scientific efforts.

The halted trial was a setback, but three other microbicide products are being tested in trials and others are in the pipeline, he said.