Protecting infants from AIDS
Interview with Professor Luc Montagnier, President of the World Foundation for Aids Research and Prevention
The HIV/AIDS virus was first identified in 1983–1984 by Professor Luc Montagnier of the Institut Pasteur (France) and Professor Robert Gallo of the National Institute of Health in Bethesda (USA).
Two main factors explain why the transmission rate of AIDS to African babies is so high. Firstly, there is the general problem of the Third World’s lack of access to medication, on account of the cost and the quasi-total absence of testing for AIDS. The problem is especially acute in Sub-Saharan Africa. As a result, very few African women infected with the AIDS virus receive any treatment at all during their pregnancy. Nor do their newborn babies.
The second factor concerns the efficacity of treatment. The reason we waited until 2002 to begin developing a pediatric vaccine is because therapeutic treatments reducing mother–child transmission already existed, so there didn’t seem to be a problem. Just before delivery, Nevirapine is administered to the mother. This treatment is relatively straightforward and may be administered over a short period. It reduces from 25% to only 3-5% the infection rate in newborns. But there is still no treatment which is 100% effective. Recently, we realized that breastfeeding reinfects the infant and that the infection rate after a year is the same as if the child had received no treatment at all.
And most African babies are breastfed…
Yes, because, thanks to the mother’s antibodies, breastfeeding offers protection from the diseases which so often kill babies in Africa. Diarrhoea, for instance, causes an enormous number of infant deaths. The problem is that mothers’ milk can contain the AIDS virus in a form we still don’t understand very well.
Our project for a pediatric vaccine targets infants infected by breastfeeding. The vaccine must be able to protect the child for the first two years of life, until it is weaned.
Infants in some West African countries are currently being vaccinated against the tuberculosis bacillus. The BCG is a living, pasturized vaccine made up of an attenuated tuberculosis bacillus. It doesn’t offer complete protection from tuberculosis but it does erect a barrier against the most serious effects. It also has a very stimulating effect on the immune system. We take advantage of this immunity to add HIV proteins – we are still choosing the most appropriate molecules – to create a pediatric vaccine against AIDS.
At what stage is your research?
We have conducted trials on mice and are presently testing the vaccine on macaques to see if we can obtain a good cellular immunity. The next step will be to begin phase 1 clinical trials on adult volunteers a year or two from now, before testing the vaccine on infants in a second phase.
These trials will be conducted on 10–20 volunteer adults from countries in the North and in Africa. This is important not only because there are variations of the AIDS virus but also because genetic variability means that different populations react in different ways to the virus. Since we are going to be using the vaccine in Côte d’Ivoire, Burkina Faso and Cameroon to begin with, the researchers working with us from these three countries have had to identify the differences in the genetic response of their respective populations.
So you are working directly with African researchers?
It is even central to the project. Our Foundation’s approach is to create centres in Africa which associate AIDS prevention, treatment and research. Each centre treats patients and, in parallel, participates actively in clinical research, including that on a pediatric vaccine. By grouping prevention, treatment and research under the same roof, the idea is to combine scientific and educational activities to ensure that both the population and the trainers are well-informed. Hence our plans to equip each centre with a multimedia training room. Each centre trains civil servants, including administrators, police and teachers, specialists and other groups. As for the researchers and doctors working in these centres, all have received, or will receive, advanced training on AIDS in either Paris, Baltimore or Rome.
The first centre was set up by the Foundation in Abidjan, Côte d’Ivoire, in 1996. We are now equipping a second centre in Ouagadougou and the Cameroon government is building a third centre in Yaoundé to serve the sub-region – as long as US$2 million can be found to equip it. Professor Gallo’s team is setting up similar centres in Nigeria and other English-speaking countries of Africa.
The Abidjan centre is headed by Dr Henri Chenal, a surgeon who was himself infected with the AIDS virus while operating. The centre has been approved by UNAIDS for the distribution of tritherapies but is financed solely by our Foundation and the Government of Côte d’Ivoire. An estimated 12% of the population is infected with the AIDS virus. Half of the declared AIDS cases in Abidjan – about 1500 people – come to the centre regularly to receive a bi- or tritherapy. Only those who can afford to pay are expected to do so. But the majority of those infected, those who have not yet fallen sick, don’t wish to know their state of health and choose to hide their illness from their entourage, out of fear of rejection or of losing their job. Unfortunately, even those who do come to the centre have often waited too long; they are already very sick with tuberculosis or other diseases and in need of hospitalizing. The problem is, there are not enough beds.
Côte d’Ivoire has a population of 16 million. That means nearly 2 million people are infected with the AIDS virus, yet you say there are only 3,000 declared cases in Abidjan?
It’s far from exceptional. Merely an estimated 1% of AIDS victims in Africa know they are infected. And even those who do take the AIDS test these days and discover they are seropositive are told to wait until they are ill to come for treatment. We want to incite people to follow treatment from the outset. But first, clinical trials need to be conducted to design treatments which are less toxic than a tritherapy for people who still have a reactive immunity system. In passing, I should explain that, if a tritherapy is administered over a long period and, above all, not on a daily basis, this can allow the virus to mutate and develop resistance to treatment. Hence the current approach of administering a tritherapy solely to patients who are already heavily infected with AIDS; we are talking about a category which represents approximately 10% of the 30 million Africans infected with the virus.
To limit the spread of the epidemic, our vaccine could also be administered to adults for therapeutic purposes via our own centres. By adding an immuno-stimulating treatment, it would be possible to reduce the dose or even halt the tritherapy altogether. That would slow down the infection’s progression and make it harder for people to pass on the virus to their sexual partners.
Are any other public or private research projects working with African researchers?
African researchers are collaborating on many projects but not, to my knowledge, on any project to develop a pediatric vaccine.
Earlier, you explained that the lack of access to medication was a major problem for the developing world. What is being done to lower the cost of medication for poor countries ?
There is already a significant difference in the price of medicines in rich and poor countries. The social security system in Western countries pays a high price for medicines so that these can be sold at lower prices to poor countries. There are also some international initiatives like the World Fund created in 2002 by the G8 and the United Nations. This Fund will make it possible to lower prices even further.
The pharmaceutical companies have also made a big effort to improve their image. Bilateral agreements have brought the cost of a tritherapy down from US$10,000 to US$300. Moreover, an agreement signed at the World Trade Organization last September will allow countries like India and Brazil to produce copies of the products manufactured by major pharmaceutical groups and to sell cheaper generic medicines for diseases such as AIDS, malaria and tuberculosis in the developing world.
If you succeed in your endeavour, do you plan to patent the pediatric vaccine and, if so, under what conditions?
The World Foundation for AIDS Research and Prevention is an NGO. As such, it is a non-profit organization. Our current project is pre-clinical and concerns solely the feasibility of a pediatric vaccine. Since UNESCO cannot engage its responsibility in the area of clinical trials, the clinical part will probably be placed under the auspices of WHO rather than under the auspices of UNESCO.
The universities involved in the project, namely those of Tor Vergata in Rome and of Maryland in Baltimore, do have policies for intellectual property protection policies, as do all universities – not to mention own Foundation for that matter – but up until now we have never envisaged this aspect. Once we move on to clinical trials on people, we may think about protecting the vaccine. Its development will either be undertaken in tandem with a pharmaceutical company or within the framework of a public project.
If we receive public support, the vaccine won’t cost patients anything. If, on the other hand, we need to enter into partnership with a pharmaceutical company for the vaccine’s manufacture, that will of course entail putting a price on the vaccine. Yet, for Africa, the cost of the treatment will need to be extremely low. At UNESCO’s General Conference last October, all countries were asked to support the project.
What level of investment will you need to complete the trials on infants?
At this stage, we need to be able to equip the centres in Burkina Faso, Cameroon and elsewhere with specialized facilities. It will take a minimum of US$6 million to complete the second clinical phase, that of trials on infants.
Generally speaking, why, when the AIDS virus was first discovered 20 years ago, is it proving so difficult to develop a vaccine to fight it?
There are several reasons. One is the variability of certain parts of the virus which enable it to dodge the body’s immune response. There is also the lack of animal models and the difficulty in testing the vaccine’s efficacity on an exposed human population – even though we are certain of its innocuousness.
In fact, it is possible to surmount these difficulties – and this is what we are attempting to do at the Foundation – by modifying the virus’s surface protein using biotechnology, in order to expose the virus’s least variable regions to the body’s immune response, and by testing the candidate vaccine first as a complementary therapy. The immune system of a patient who has already been treated with a tritherapy is sufficiently restored to respond well to the vaccine. Whether or not the vaccine works will be determined by whether or not the virus begins to multiply once more after we stop the tritherapy. If the virus doesn’t begin multiplying again, we will know we have a good candidate for a preventive vaccine.
Is the project well under way?
We would be able to progress faster with more substantial financial means.
Interview by Susan Schneegans