Bangkok Post - Monday, July 8, 2002
Anjira Assavandona

The trial, set tentatively to begin before the end of the year, will involve 16,000 volunteers not infected with HIV.

This would be the 11th vaccine trial since 1991, when the first national plan for HIV/Aids vaccine development came into being.

There are more than 30 candidate vaccines being tested worldwide, most still at the first or second phase. The trial planned for Thailand will be the first to reach anywhere near its expected scale.

The trial is a collaboration between the Ministry of Public Health, the US Military HIV Research Programme, Mahidol University, the army's Medical Department, the Henry Jackson Foundation, Aventis Pasteur, VaxGen and the US National Institute of Allergy and Infectious Diseases. Funding is to be provided equally by the Thai and US governments.

Dr Supachai Rerk-ngarm, the man in charge of the project, said last week the trial would use the random, double blind, placebo-controlled method, and was expected to take more than five years. It seeks to determine the effectiveness of a prime-boost combination using ALVAC-HIV (vCP1521), a canary pox vaccine developed by Aventis Pasteur, as the prime, followed by a boost of the AIDSVAX-B/E vaccine made by VaxGen.

The two vaccines have been tested with thousands of people globally and have recorded promising results in Phase I safety and Phase II safety and immunogenicity trials.

ALVAC-HIV is a live recombinant canary pox vector that does not cause illness in humans. The vaccine is designed to work against a primary sub-type E isolate, which is specific to the HIV clade prevalent in Thailand. The canary pox will stimulate cellular immunity by activating Cytotoxic T lymphocytes, which recognise and kill cells infected with HIV.

AIDSVAX B/E is a sub-unit vaccine candidate that stimulates humoral immunity, producing antibodies. These antibodies are designed to attach to the protein on the virus surface that HIV uses to fuse through and infect healthy cells. If the antibodies can prevent the virus from attaching to healthy cells, it is believed they can prevent infection.

AIDSVAX B/E also targets the strains of HIV prevalent in Thailand and neighbouring countries, and it, too, cannot cause infection because it is made of genetically engineered proteins.

The ultimate hope for this trial is that both arms of the immune system _ cellular and humoral _ are stimulated, resulting in protection against infected cells and a freely circulating virus.

According to Dr Supachai, agencies within the Thai government and the US Military HIV Research Programme have collaborated for more than a decade to build the infrastructure to support a large-scale efficacy trial.

Dr Deborah Birx, director of the US Military HIV Research Programme, has described the Phase III trial as a milestone in the long journey towards an Aids vaccine.

``The Thai approach is a model for the world, which is evident in the fact that our programme is bringing the same capabilities and approaches to Africa,'' Dr Birx said.

The trial protocol calls for 16,000 volunteers not infected with HIV from eight districts of Chon Buri and Rayong provinces. They must be aged 20-30 years. Half the trial participants will receive four doses of ALVAC-HIV _ the first, then again after one, three and six months _ as the prime along with doses of AIDSVAX B/E after three and six months as the boost. The other half will receive placebo injections on all four vaccination visits.

The trial is still pending final approval here and the US. Here, the Technical Sub-committee on Aids Vaccines under the National Aids Commission and the Public Health Ministry will meet soon for a final review of the trial.

The trial is expected to begin towards the end of this year and the enrolment of volunteers a further 12 months. All volunteers will receive extensive counselling on HIV risk avoidance. The immunisation phase will take six months, with follow-ups over the following three years.

The volunteers will have their blood tested every six months after vaccination to determine whether they have become infected with HIV.

The trial is expected to conclude in 2007, with final analysis in 2008. There will be one interim analysis, after approximately three years. An international data safety monitoring board will oversee the trial and conduct quarterly safety reviews.

Dr Vallop Thaineau, director-general of the Communicable Diseases Control Department, said Thailand, like many developing countries, needed an HIV vaccine urgently to supplement its intervention measures.

Although the HIV infection rate fell to 29,000 last year from 143,000 in 1991, this is still too high and there are indications the virus is now spreading through the adolescent population. Prevention efforts, including advice on condom use, the distribution of clean needles, peer counselling and the provision of anti-retroviral treatments to reduce mother-to-child transmission, have only slowed the spread of the virus, not stopped it. Development of a vaccine is seen as the most powerful and cost-effective intervention.

As a co-partner in this project, Thailand will have priority in receiving the vaccine if it proves successful.

Dr Vallop said the trial would be carried out to the highest international scientific and ethical standards. He said transparency would be emphasised at all times, and there were plans to include non-governmental organisations and the community at every step.

``We want this to be a true partnership between the medical community, the NGOs, the community and the government, as well as our international collaborators,'' he said.

The aim is for the community to better understand HIV/Aids, preventive measures and all aspects of vaccine development, especially their rights as volunteers.

A process of informed consent will apply to ensure participants understand all the details, such as why the research is being done, what the researchers want to accomplish, what will be done during the course of the trial, what risks are involved, what benefits can be expected from the trial, what other interventions are available, and the participants' right to leave the trial at any time.

Dr Supachai said Thailand, as a co-developer of the vaccine, would probably be able to make the vaccine available to its citizens at a cheap price.

Dr Vallop said a viable vaccine approach was the key to Thailand's long commitment to developing ways to stem HIV/Aids .

The announcement of this advanced trial in Barcelona is of enormous significance, he said. It would bring Thailand to world attention in the fight against Aids, and would improve its credibility as the host of the next International HIV Conference set for Bangkok in 2004.

There is more work to be done and more challenges yet to overcome before that next summit. But a start could be made through strong political support, the dedication of scientists from both the private and public sectors and community involvement in moving the country forward along the road to better dealing with HIV/Aids.
020708
BP020706

Always watch for outdated information. This article first appeared in 2002. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 2002. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .