Disappointed But Undaunted
Researchers remain upbeat on AIDS vaccine prospects despite AIDSVAX mass trial failure
By Richard Ingham and Pascal Barollier
Agence France Presse
PARIS
The failure of the first mass trial on an AIDS vaccine may have come as a disappointment to many, but it has not discouraged AIDS fighters from their quest to produce the hoped for shield against the global pandemic.
"The news on VaxGen's AIDSVAX is disappointing, but we are not discouraged," said Seth Berkley, president of the New York-based International AIDS Vaccine Initiative (IAVI). "The search for an AIDS vaccine will-and must-go on. A vaccine is the world's best hope to end the spread of a virus that infects nearly 15,000 men, women and children daily and threatens the survival of whole communities."
Berkley said scientists remain confident that an AIDS vaccine is possible, adding that alternative vaccines, employing different design strategies, are now in development, and some have already entered human trials. "These must move forward through further study, without delay."
About 30 potential vaccines are at various stages of development. Most are therapeutic and to be taken after infection.
Researchers described HIV as a devious foe and this had been confirmed by the setbacks encountered by AIDSVAX, the first vaccine to be assessed on thousands of volunteers. A senior European researcher said AIDSVAX was "the first generation" of prototype vaccines and many had already doubted privately that it would work.
"It is a disappointment but, for scientists, not a surprise," said Jean-Gerard Guillet, head of the preventive vaccine program at ANRS, France's National AIDS Research Agency. "We have known since the beginning that antibody-based vaccine strategies will not be enough to fight the incredible diversity of this virus," he said.
Priming
AIDSVAX primes antibodies, the frontline soldiers in the body's immune system. Its aim is to get the antibodies to spot the so-called gp120 protein on the surface of HIV, which enables the virus to dock with an immune-system cell, the first stage before penetrating it.
Guillet said many AIDS vaccine researchers are turning away from antibodies and focusing instead on cellular immunity: getting killer lymphocytes to seek and destroy HIV-infected cells. This would not, however, destroy the virus in the bloodstream, which means it could still infect other people through, for instance, shared drug syringes.
Preliminary results unveiled late February by AIDSVAX makers, VaxGen Inc., showed that the vaccine provided "approximate efficacy" of only 3.8 percent among 5,009 volunteers in North America, Puerto Rico, and the Netherlands who were given three injections over three years.
That compares with hopes that it would be at least 30-percent effective, a level that could have warranted distributing it around the world as an adjunct to safe-sex techniques.
VaxGen, while acknowledging that the trial had failed to meet the primary goal, contended it saw some good news-the vaccine may be more effective for several ethnic groups. Among "nonwhite" volunteers, the efficacy rate was 67 percent, and it was highest among blacks, at 78 percent, it said.
"This is the first time we have specific numbers to suggest that a vaccine has prevented HIV infection in humans," said Phillip Berman, AIDSVAX inventor and VaxGen senior vice president of research and development. "We're not sure yet why certain groups have a better immune response, but these preliminary results indicate that a surface protein that stimulates neutralizing antibodies correlates with prevention of infection."
That contention met with a nuanced response elsewhere. The consensus was that the apparent protection for ethnic volunteers was intriguing and deserved further inquiry. But no observer agreed with the conclusion, implied by VaxGen, that genetic differences may have helped blacks and Asians to respond better to the vaccine.
Peter Piot executive director of the UNAIDS, the UN agency fighting the global AIDS pandemic, said those figures on ethnic volunteers were "promising" and warranted "urgent... targeted research" to find out more.
The International AIDS Vaccine Initiative (IAVI), a New York-based organization pushing to promote a vaccine against HIV, also questioned the conclusion, saying the number of infections among ethnic volunteers was too small to draw any firm conclusion.
Berkley said the number of infected blacks was only 13, four of whom were in the vaccine group while nine were in a group that received a dummy lookalike, and the number of infected Asians was just four, with two in each group. Such small figures meant that it was impossible to rule out statistical anomalies or that blacks and Asians had responded better to the safe-sex counseling given to all of the volunteers, he said.
There was indeed a theoretical possibility of genetic differences, but this had to be demonstrated clinically, Berkley said.
For instance, blood samples, taken from the blacks and Asians, would have to prove that these volunteers had had a better immune response to the vaccine, he said.
Peter Piot, executive director of the UN agency UNAIDS, said some of the results were "promising." "The trial provides clear evidence that a vaccine can work. However, there is an urgent need for more targeted research to find out why the candidate vaccine only seems to work in certain population sub-groups."
Two-thirds of the 5,009 volunteers, primarily gay men in the US, Canada, Puerto Rico, and the Netherlands, were given the vaccine, and one-third placebo.
A Phase III trial of AIDSVAX is also underway among injection drug users in Thailand, testing a formulation that is designed to protect against the HIV subtypes B, prevalent in North America and Europe, and E, which is prevalent in central Africa and Southeast and East Asia.
Malaysia Turns to Herbs
KUALA LUMPUR
A Malaysian herbal formula is being studied for its effectiveness as a complementary treatment to help HIV/AIDS victims enjoy a longer and better quality of life.
Health Minister Chua Jui Meng said a longer trial would be conducted to find out if the herbal formulation was safe and effective following encouraging preliminary results achieved from a clinical trial on 10 patients. Chua said that positive results were recorded from a six-month controlled trial performed last year on 10 HIV/AIDS patients, using a special formula put together by a local researcher.
Out of the ten patients, nine had CD 4 immune cell counts of below 200, which meant that they were categorized to be suffering from AIDS-the last phase of the disease, he said. "At the end of the trial, four patients had shown a decrease in viral load and out of these four, one patient had an increase in body weight and improvement in CD 4 counts. This patient, who had already gone back to work, continued therapy and on the 47th week had shown a sustained low viral load level."
Chua said the patient remained well throughout the duration of the therapy with no reported adverse reactions. He did not reveal the herbs used in the trial.
The positive results had encouraged health authorities to embark on a two-year trial period with more patients, he said.
"We are hopeful for better results with the new trials as we can study if the local formulation can be used as maintenance therapy in combination with Western drugs and anti-retroviral drugs," he added.
Chua said the herbal formula could also help patients cope with the disease, as some had not been able to withstand the side effects of the anti-retroviral drugs.
Malaysia reported 40,049 HIV cases, 5,103 AIDS cases and 3,881 deaths from 1986 to April 2001.
AFP
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