Vaccine research needs to cover all bases
To address the urgency of the HIV crisis, says Mauro Schechter, vaccine researchers must pursue clinical trials as well as basic science, testing vaccines for both prevention and therapy.
Global vaccine strategy
HIV vaccine researchers really have to learn to crawl and walk at the same time. We need to understand more about the basic science of HIV/AIDS to produce a vaccine, but we do not have the luxury of time. Because HIV/AIDS is a global emergency and a complex problem we have to try unorthodox solutions.
We could argue endlessly about which of the different strategies currently underway in HIV vaccine research will work or not, but no one knows for sure. The difficulty is in how to move forward quickly with multiple approaches, knowing that we cannot wait for the results of one trial before starting the next. The results of 'trial A' might show that 'trial B' is nonsensical, but we will know that only with the benefit of hindsight.
For example, controversy has arisen over the current phase 3 HIV vaccine trial in Thailand. It would do more harm than good to halt an ongoing trial when many reasonable and knowledgeable people think it might work. My guess is that it probably will not, but that is just a guess. Only the future will tell.
There are groups such as the Global Vaccine Enterprise, with which I have been peripherally involved, who are trying to coordinate initiatives to ensure minimal overlap and repetition. But as well as coordination, there needs to be healthy competition, because researchers are only human, and like to compete.
In Brazil, where around 660,000 people are living with the disease, people have a sense that HIV/AIDS is an important health problem and that a vaccine is needed. These are the positive effects of the country's national HIV/AIDS treatment and awareness programmes. Although the availability of free treatment makes some people more complacent about taking risks it does not hamper enthusiasm for vaccine development.
We created a vaccine trial site in Rio de Janeiro in 1994 as part of what is now the HIV Vaccine Trials Network (HVTN). Our vaccine research site deals with men who have sex with men and high-risk heterosexual young men and women. The incidence rates in these groups are stable, and offer the potential for conducting large trials. We have just finished one trial, and have an ongoing phase 1 safety study using a Merck adenovirus-based (i.e. DNA-based) vaccine. We are about to start another HVTN phase 1 trial of two different vectors (viruses that carry the HIV virus in the form of a vaccine), fowlpox and vaccinia, aimed at triggering the cellular arm of the immune system.
At my research site we try, as far as possible, to do both preventive and treatment research. If we do only preventive research, we may be seen as neglecting the infected community, and vice versa. Doing both is crucial for progress in fighting HIV/AIDS. This is why research into therapeutic vaccines is needed – even though its prospects are debatable from a scientific perspective.
HVTN is now planning to move into phase 2b trials, which test whether the drug is likely to be effective in treating HIV/AIDS. We will probably be joining one of these in late 2005 or early 2006. Overall, the trials will involve 3,000 participants in several sites, with several hundred of these in Brazil.
Drive for personnel
The main factor limiting research in most developing countries is personnel. At our research centre we have developed a system that has enabled us to grow steadily over the last few years. We now have a team large enough to follow several hundred people. But to conduct a phase 3 trial (testing whether or not a drug is effective and safe) involving several hundred or a thousand volunteers we would need to recruit more trained staff.
One of our biggest challenges is identifying young individuals who want to do research. Because Brazil has no real tradition of research, people do not know or think about it. When clinicians are at medical school they all think about practising — in the emergency room, in private practice, or like a doctor they have seen on television.
Research is not part of our culture, and there's only a small market for it. To tackle this we have established a close relationship with various schools at the Federal University of Rio de Janeiro and we're trying to recruit fresh nurses, pharmacists and physicians from them.
Other countries in South America are now getting more involved in HIV vaccine research and through the HVTN network we are helping establish new research sites in San Paulo, Brazil, and Jamaica. Regardless of differences between countries, many of the problems involved in doing research are surprisingly similar. Experiences really can be shared, which saves time and effort, particularly in recruiting and retaining volunteers.
Looking ahead to the Rio conference
I am particularly interested in one session at the International AIDS Society conference in Rio (24–27 July): a forum on generics and brand-named drugs, which has broad implications not only for treatment but also for vaccines.
The issue of intellectual property rights is a major area of contention — they can be used either to inhibit or motivate development. Creating incentives for development is a trick that so far, on a small scale, the International AIDS Vaccine Initiative (IAVI) has mastered quite well by funding vaccine development on the condition that resulting vaccines would be made available in the developing world at a 'reasonable price'.
But on a larger scale, the world has to reconcile the need for financial rewards — which motivate companies to make new products — with the rights of people to be treated with whatever drugs and vaccines exist.
Interview by Julie Clayton
Mauro Schechter is professor of infectious diseases and head of the AIDS Research Laboratory at the Federal University of Rio de Janeiro, Brazil. His work on HIV/AIDS includes overseeing clinical trials for the HIV Vaccines Trials Network. He is also an advisor to the International AIDS Vaccine Initiative (IAVI), and co-chair of the forthcoming International AIDS Society meeting on HIV Pathogenesis and Treatment in Rio de Janeiro, 24-27 July 2005.
Read more about HIV/AIDS vaccines in SciDev's HIV/AIDS vaccines spotlight.