When findings for the largest-ever HIV/AIDS vaccine trial were released at the end of September 2009 it was heralded as an "historic day" in the search for a medicine to stop the spread of infection around the world.
The study was far from conclusive but on the back of a number of failures by big pharma in this field the results are being taken as a positive breakthrough in a previous black-hole area of medicine.
The trial of more than 16,000 volunteers in Thailand was the first trial in which infection has been prevented, according to the US Military HIV Research Program. The prime boost trial – where the first compound is given to prime the immune system to attack the virus and the second strengthens the response – was found to lower the result of infection by 31.2%.
The trial, funded by the National Institutes of Allergy and Infectious Diseases, involved giving multiple compounds to half of the HIV-negative study group.
The others – also HIV-free – were given a placebo. Each volunteer was given counselling and condoms to prevent them contracting the infection. Over the course of the trial, 51 of the 8,197 people given the vaccine contracted HIV compared with 74 of the 8,198 people given the placebo.
Although the result did not reach the vaccine effect of 50% or higher that would have triggered the trial team to apply for a licensure application, the results are being deemed significant.
AIDS Vaccine Advocacy Coalition executive director Mitchell Warren says that the trial represents the possibility to reduce the risk of HIV infection with a vaccine. "These results move us one step further along in the marathon journey of AIDS vaccine research that continues," he says.
"They also demonstrate that the scientific process is remarkable and unpredictable and underscores the need for testing strategies in human efficacy trials. There is little doubt that this finding will energise and redirect the AIDS vaccine field as all of us begin the hard work to translate this landmark result into a true public health benefit."
Few details of the trial have been released to date and experts around the world are waiting to conduct detailed analysis of what the real benefits are likely to be. The trial sponsors will present more detailed results at the AIDS Vaccine Conference on 19–22 October in Paris, France.
What is known is that the trial was a Phase III prime-boost trial of Sanofi Pasteur's live recombinant ALVAC-HIV and Global Solutions for Infectious Diseases' AIDSVAX B/E (originally developed by VaxGen). AIDSVAX was developed to generate anti-HIV antibodies and had been previously tested on its own in efficacy studies in North American and Europe, but failed to show signs of protection. In this trial, the vaccine candidate was combined with ALVAC – developed to generate cell-mediated immune responses – and is based on HIV strains B and E, which are dominant in Thailand.
A spokesperson from the International AIDS Vaccine Initiative (IAVI), that works to support in every way the development of preventive AIDS vaccines, told pharmaceutical-technology.com that the trial differs from all before as it is the only one that demonstrated an AIDS vaccine provided a benefit in humans. "This gives researchers a platform on which to improve and give positive results to validate assays and animal models," the spokesperson said.
The trial does indeed have a unique air about it. The only other still ongoing trial evaluating the efficacy of an AIDS vaccine candidate is a Phase II study called HVTN 505, despite there being some 30 other AIDS vaccine candidates worldwide in early Phase I/IIa clinical trials. HVTN 505 is evaluating the safety and effectiveness of HIV-1 DNA plasmid vaccine and HIV-1 recombinant adenoviral vector vaccine in HIV-uninfected, circumcised men.
For the community at large, however, more information is needed to assess just how important the findings are. Frost and Sullivan programme leader of pharmaceuticals and biotechnology life sciences Shabeer Hussain says that given these facts and the initial findings released the signs are positive. "For the research community it is a great success and we should appreciate their work. But we need more information about how they will follow it up," Hussain says.
Hussain says that the length of time it takes for the virus to develop raises the question as to whether some of the subjects could have contracted it before the trial began. When more detail is given, questions such as these will be answered but a series of others are likely to be raised over how the researchers will move forward with the study.
For the IAVI spokesperson the trial has confirmed that future studies should focus on giving vaccines to humans. "While pre-clinical data can provide important clues for the identification of the most promising AIDS vaccine candidates, testing of these candidates in human trials provides critical answers that cannot be addressed by preclinical studies," the spokesperson said. "This is especially true since the correlates of immunity are not known for an AIDS vaccine."
What is clear is that the news is likely to reinvigorate the pharmaceutical sector to look at finding a HIV/AIDS vaccine as a more realistic area in which to focus their efforts and money. "During the economic crisis, companies have not been investing heavily in an HIV vaccine even though it as a huge population base," Hussain says.
The study showed a significant impact in candidates in Thailand with a specific strain prevalent in that region. It is likely, therefore, that the compound combination will need to alter for different strains in varying regions. Although this is a positive step, finding a universal vaccine that, most critically, can be deployed around the world at an affordable cost is still a long way off.