Global Solutions for Infectious Diseases (”GSID”) announced today that a Phase III clinical trial of an investigational HIV vaccine regimen has been shown to be safe and modestly effective in preventing HIV infection. The double-blind, placebo controlled study was conducted in Thailand among more than 16,000 volunteers.

The clinical trial (RV 144), the world’s largest study of an HIV/AIDS vaccine regimen, demonstrated that the combination of a priming vaccine developed by sanofi pasteur (ALVAC®HIV vCP1521) and GSID’s boosting vaccine (AIDSVAX®B/E) reduced HIV infection in a community-based population by 31.2% compared with placebo. In the final analysis of the trial, 74 placebo recipients became infected with HIV compared to 51 vaccine recipients. The efficacy result is considered statistically significant with a p-value of 0.04 and a 95% confidence interval having a lower bound greater than zero.

Additional research will be required to clarify the public health benefits of this outcome, including whether boosters would be needed and whether the vaccine combination would yield the same results against different strains of the virus found in other parts of the world. One of the most critical steps now will be to manufacture new lots of AIDSVAX for a variety of possible future studies in combination with ALVAC. GSID will make AIDSVAX at a qualified contract manufacturer.

“As the first HIV vaccine trial to demonstrate some level of reduced infection among the entire trial population, this is an encouraging step forward in the struggle to develop an effective HIV/AIDS vaccine,” said Donald Francis, M.D., D.Sc., GSID’s executive director. “This trial will provide researchers with valuable data and insights to continue the development of a vaccine that can hopefully one day eradicate this terrible disease.”

He congratulated the Thai Ministry of Public Health and the U.S. Army who collaborated to make this trial successful, and further expressed his appreciation to the National Institute of Allergy and Infectious Diseases (NIAID) for its scientific and financial support.

The vaccine combination tested in Thailand was developed based on the strains of HIV that circulate in that country. Separate versions of the vaccine may have to be manufactured and developed for HIV strains that predominate elsewhere in the world, including North America. The Thai study, which began in 2003, was designed to test the vaccine regimen’s ability to prevent HIV infection, as well as its ability to reduce the amount of HIV in the blood of those who became infected during the trial. The study did not show a statistically significant result in reducing the viral load in the HIV-infected volunteers.

After initial development at Genentech, the AIDSVAX technology was transferred to VaxGen Inc., which completed two Phase III trials of AIDSVAX alone in high risk populations in Thailand, North America and Europe in 2003. Both trials did not show a statistically significant reduction in HIV infection overall. GSID obtained certain intellectual property and manufacturing rights related to AIDSVAX in 2008.

Thai Trial Summary

The trial included non-infected volunteers between 18 and 30 years of age who were at average risk of HIV infection. Approximately 40% of the volunteers were women. Volunteers who acquired HIV infection during the trial were given free access to HIV care and treatment, including highly active antiretroviral therapy (HAART), according to the guidelines of the Thai Ministry of Public Health.

The study was made possible by an international collaboration involving numerous partners from the Thai and U.S. governments, private-sector companies and non-profit organizations.

“This study is encouraging not only for the outcome but for the extraordinary cooperation among the numerous entities that joined in this effort,” Francis said. “We look forward to continuing our collaboration with our partners in Thailand, the U.S. government and the private sector to advance this product. I also want to offer my personal gratitude to the more than 16,000 Thai volunteers who stepped forward to participate in this study and stayed with it for six years. They are the real heroes today.”

Source
Global Solutions for Infectious Diseases

A U.S.-backed vaccine experiment in Thailand has for the first time demonstrated a “small but measurable” benefit in preventing HIV infection, the Washington Post reports (Brown, Washington Post, 9/24). Col. Jerome Kim, a physician involved with the trial who is manager of the army’s HIV vaccine program, said that although the reduction in transmission was small, it is statistically significant and means the vaccine was 31.2% effective (McNeil, New York Times, 9/25). According to the Post, the “chief usefulness” of the vaccine is “likely to be what it can teach virologists about what is happening in the immune system when a person is even somewhat protected from HIV.” The vaccine is not expected to be licensed or produced in large amounts, and it is unlikely that countries would consider it effective enough to be used as a public health measure to reduce the spread of HIV. Nonetheless, the findings are considered a milestone, as they mark the first positive results of an HIV vaccine after two decades of experiments (Washington Post, 9/24).

The vaccine combines Sanofi-Pasteur’s ALVAC canary pox vaccine and AIDSVAX, a failed HIV vaccine made by VaxGen, which is owned by the not-for-profit Global Solutions for Infectious Diseases (Fox, Reuters, 9/24). The six-year study involved 16,000 Thai men and women and was run by the U.S. Army, NIH and Thailand’s Ministry of Public Health. According to the Post, about 40% of the participants were women, and many were employed in shipping and manufacturing enterprises along the Thai coast. A few were injection drug users and men who have sex with men — two groups considered at high risk for HIV transmission. Researchers randomly assigned participants to receive the vaccine or a placebo. Participants were counseled on methods of HIV prevention and advised to use condoms (Washington Post, 9/24).

The participants received six immunizations over six months, two with AIDSVAX and four with ALVAC (Reuters, 9/24). Fifty-one of the 8,197 vaccinated people became infected with HIV in the three years after the shots, compared with 74 of the 8,198 people who received placebos (Washington Post, 9/24). Further details of the study, which cost $105 million, will be presented at a vaccine conference in Paris in October (Marchione, AP/San Francisco Chronicle, 9/24).

Researchers said the vaccine, known as RV 144, “protected too few people to be declared an unqualified success,” and they were also “puzzled” by the trial’s results because the vaccine did not change the amount of HIV in a person’s blood compared with someone who received a placebo, the New York Times reports. A vaccine that offers partial protection typically lowers the viral load. However, this did not occur in the trial, which suggests that the vaccine does not produce neutralizing antibodies — which attack virus cells — like most vaccines, according to Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, which paid for most of the trial. He said the vaccine may produce “binding antibodies,” which attach themselves to and empower effector cells, a type of white blood cell attacking the virus (McNeil, New York Times, 9/25).

Fauci said, “Conceptually, we know a vaccine is possible,” adding, “Whether the vaccine is going to look anything like this one, I don’t know. But at least we know it can be done” (Washington Post, 9/24). Mitchell Warren, executive director of AVAC, the AIDS Vaccine Advocacy Coalition, said that the results of the study are “hugely exciting and, frankly, unexpected,” adding that although RV 144 “is not the vaccine that ends the epidemic,” it is “a fabulous new step that takes us in a new direction” (New York Times, 9/25).

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