Mitchell Warren,
Executive Director, AIDS Vaccine Advocacy Coalition
The focus in recent
years, in the US particularly, has been on the 'ABC' approach - time has
been wasted discussing A or B or C or others, when we should be
concentrating on tackling HIV which has been with us now for 25 years.
Two key points to
make: new prevention technologies will not come soon enough. And they are
not designed to replace existing prevention methods, but to complement
them. We must not lose sight of what we have today to prevent HIV, but
existing tools, after 25 years, are not enough and we need new prevention
technologies.
At present, several
products are in late stage efficacy trials - but these products take years
to develop. We are talking this evening about products that are in Phase
III trials, but don't forget that there are still many products coming in
to the early stages of development. The world has spent roughly $800
million in pursuit of and AIDS vaccine. Compared to the female condom,
this is a lot - but against obesity, some cancers and erectile
dysfunction, for instance, it pales in comparison.
There are around 30
candidate vaccines in the world now, mainly funded by developed countries.
A few years ago the science was taking place only in these developed
countries, but now India, Africa and Brazil are joining the US, Canada and
Europe - it is a global effort. These are exciting times for the
development of new prevention technologies - not just vaccines and
microbicides. We are looking at a seismic shift in tackling HIV in the
next five years.
Male circumcision -
trials in Kenya and Uganda are due to report in the next six months. If
those two trials support the results of the trial in South Africa last
year, it will change the way we tackle HIV. And in around eight months'
time, results of a diaphragm trial are expected. But we must be aware that
both of these trials may not be successful, and have to prepare for that
too.
Microbicide trial
results are expected in 2007 and 2008, as are results of trials looking at
behavioural intervention and suppression of the herpes simplex virus and
its effect on HIV. In 2009 another microbicide efficacy trial will be
completed, and pre-exposure prophylaxis (PREP) trial results will be
available. We need to plan in advance, in case PREP works.
A Phase IIb vaccine
trial is taking place in the US and Latin America, and in early 2007 a
parallel trial will begin in South Africa, hoping to show cell-mediated
immunity. A vaccine trial in Thailand involving 16,000 people will report
in 2010.
So what will we know
in five years' time, when these trials have reported? We will know that
research and development is global, and that it is a long and costly
process. We will know that trials can successfully be done. We will know
that new prevention technologies will work some of the time for some
people - i.e. that they will be partially effective. A combination of
partially effective products may break the back of the epidemic. The
bottom line is that no one product will replace another.
Think about AZT: now,
nobody would ask for monotherapy, but of course they did when it first
became available. The second and third generation of vaccine and
microbicide products could make things more complex. This is not meant to
dishearten people, but it is important to make clear what will happen.
Currently, new prevention technologies (NPTs) are tested against existing
prevention options. But if early versions of NPTs are successful, these
will become the products to test against, making trials more complex.
Regarding vaccines, we
are doing a better job of asking the right questions now, even if we
aren't yet able to answer them. The Global Vaccine Enterprise involves
most of the main scientific entities and, remarkably, organisations are
recognising than it is unlikely that one entity or organisation can find a
vaccine alone. The Enterprise is a work in progress, but is likely to help
ensure we are looking for a vaccine in the best way.
The AIDS Vaccine
Advocacy Coalition (AVAC) has existed for 11 years - the focus is on
advocacy. The search for an AIDS Vaccine is a greater challenge than
sending a man to the moon - in the space race, we knew where the moon was,
and roughly how to get there. It was essentially an engineering problem.
With a vaccine, we don't know where the 'moon' is yet, but we know what
AIDS is and we must make the search for a vaccine an engineering question
too.
Looking forward -
there will be more trials, more scientific breakthroughs and perhaps some
setbacks in the future, but the road is better mapped than it ever has
been.
Sheena McCormack,
Chief Investigator for the Microbicides Development Programme Phase III
clinical trial
Four key themes in
this presentation: the case for vaginal microbicides; status of research;
managing expectations; and access.
In some of the six
Microbicides Development Programme (MDP) trial sites, as many as one in
two women screen positive for HIV. In London, we simply couldn't cope if
50% of the sexually active women had HIV, in spite of the high number of
best-trained doctors in the world.
Ninety per cent of
women will want to have children, so condoms are not an option for them.
Women are more
vulnerable to all STIs, not just HIV, due to biological factors and to
gender inequity. Women are the face of the HIV epidemic. Even women who
are independent and socially active are often unable to challenge the
male-female imbalance. Gender equality legislation helps, but it takes
time to see change. Women also bear the burden of caring – for the sick,
the dying and for children - although it doesn't feel like this when you
meet them.
There is an urgent
need to find methods that women can initiate to protect themselves from
HIV.
Sheena was asked at
another meeting last week where microbicides could be obtained, so
explained from the outset that there isn't yet a licensed microbicide
available. They are currently under investigation, with four products in
the final stages of testing: Buffergel, Carraguard, Cellulose Sulphate and
PRO2000. Buffergel works by maintaining acidity levels in the vagina, and
the other three work by blocking the entry of HIV.
All of those four gels
are inserted with an applicator up to an hour before sex. They don't
damage human cells in laboratory experiments. Different delivery methods
are likely to become available later, but we need proof of concept that
the gels work first.
Herpes simplex virus (HSV)
is a clear co-factor of HIV. Gels that block other viruses, particularly
HSV, may reduce the likelihood of HIV infection occurring. And two
anti-HIV drugs are also in development: TMC120, being developed by IPM,
and Tenofovir. Trials for Tenofovir as a vaginal gel are currently
enrolling people. These two products could potentially be used in vaginal
rings.
We can try to estimate
biological efficacy by looking at women who reported consistent use of the
gel during a trial, and through mathematical models, but these methods are
dependent on behavioural data which we know can be unreliably reported. In
a vaccine trial, you know exactly who has been given a product, whereas a
challenge of a microbicides trial is that you have to rely on what a trial
participant tells you.
Each trial is designed
differently, but all are dependent on the rate of new infections (or
incidence) and the effectiveness of the gel. If the MDP trials achieve 40%
effectiveness, scientists would be pleased and the product could be put
forward for licensing, although whether to grant a license is the decision
of licensing authorities.
Microbicides are
expected to be partially effective - we should not dismiss partially
effective technologies, for example antiretroviral drugs (ARVs) are not a
cure, but they do make a difference to people's lives.
Benefits of
microbicides are that most women like using them, and so do their men!
Reported condom use has also increased in the trials. Women who reported
either never or inconsistently using condoms before are now reporting that
they do use them. In addition to counselling, which all women in trials
receive, taking home a trial gel could have initiated a conversation with
a partner that hadn't happened before.
Managing expectations
of women and of men in communities is very important, especially when
people are desperate for an anti-HIV product. It is important to have real
dialogue in the community, with structures that help to reach women -
especially in communities that are usually structured around men.
In 2001 when the MDP
trial started, voluntary counselling and testing (VCT) was available, but
nobody was taking it up. Trials of prevention products increase the take
up of VCT too.
Even if the
microbicide gels being tested do not eventually work, communities will
have benefited from interventions that have already taken place.
In terms of access -
we must start considering scale-up for if the product is licensed. At
present, parts of applicators are attached by hand on a production line in
Texas! But even if the current trials are successful, further testing will
be required, such as for rectal safety and safety of use by adolescents
and pregnant women. If vaginal microbicides are successful, they will open
the door to rectal microbicides and combination microbicides (that have
more than one mechanism of use) too. Hopefully big pharmaceutical
companies will get involved in this.
·
The fact there will be
a vaccine is promising, but we can't take our eye off other prevention
options. What are the implications for public policy?
·
(Requested more
information about research on circumcision, and) what will be the
availability of microbicides in developed countries?
·
In relation to
community preparedness - how much have the Department of Health prepared
communities in the UK for microbicides?
·
How will we ensure
that products get to those who need them - how will patents affect access?
And what about affordable pricing?
·
We've been waiting for
over ten years for vaccines and microbicides. Why is it taking so long,
and why do they cost so much?
·
How do researchers
ensure trials are ethical, and how do trial participants understand
exactly what they are involved in?
·
How can we balance
development of new prevention technologies with other needs, e.g. good
nutrition, and prevention of mother-to-child transmission?
·
When building trial
infrastructure, do researchers look at the social context of the area?
·
What will the impact
of Gates funding be on research? And are vaccine and microbicide
researchers working together?
·
Rectal microbicides -
is anything in development?
·
There's still a need
to increase the use of existing prevention methods, e.g. female condoms -
is there any way of linking this to the introduction of microbicides?
·
What about the social
science side of trials?
Responses to the
questions above included the following:
The biggest thing
we've seen in 2006 is the licensing of a cervical cancer vaccine. If in
the next five years we can answer some of the questions raised in relation
to the HPV vaccine (e.g. delivery to young people, patents, availability
and access), it will change the dynamic for how microbicides and vaccines
will be delivered. Cannot say exactly how long it will take for new
prevention technologies to be developed, but if we don't get NPTs, it will
become increasingly expensive to tackle HIV.
It is a travesty that
we know how to prevent mother to child transmission and infection of
injecting drug users, and we are not doing enough. But it does not mean
that because we are failing at those, we should not develop future
technologies. We need to pressurise governments to act.
We need to scale up
existing intervention, and also develop new ones. The international
community needs to think through future financing mechanisms - political
commitment is needed for the long-term.
In terms of mother to
child transmission, many women rarely or never have contact with health
care and many are afraid of HIV tests. As was mentioned earlier, voluntary
counselling and testing services have been available in many areas but
they are not always taken up. In terms of microbicides being available in
Europe - women are already reporting that they like them, so they could
potentially be marketed here as sexual pleasure products, for instance.
It will be important
to get a license for microbicides from the US Food and Drug
Administration, as this will help mobilise US funding to get microbicides
and other technologies to those who need them.
In terms of access -
thinking about distribution on the ground is important, and this needs to
be done at an early stage. Issues of scaling up will come to all aspects
of HIV prevention eventually, whether mother to child transmission, or
microbicides, or other products. Unless we invest in research and
development for the long term, we will never effectively tackle HIV.
Science has to keep up with genetic mutation for many drugs - the world
needs better malaria drugs, for instance, and we're already seeing the
emergence of extreme drug resistant tuberculosis. We must all do better.
Funding - it costs
money to do trials properly. If we want to provide trial participants with
existing prevention technologies, and counselling, and access to
treatment, money is needed. Effective trials cannot be done cheaply.
Circumcision - the
trial in South Africa suggested that in areas where circumcision is
practised as a ritual tradition, rates of HIV seemed to be lower. Data
from the current trials in Kenya and Uganda are expected in 2007. It is
important to note that people thinking that 'I'm circumcised, therefore I
must be HIV negative' could be a dangerous development, and that we will
also need an army of trained health workers to carry out the circumcision
procedure.
Ethics of trials -
trials are carried out in developing countries under the same 'Good
Clinical Practice' standards as in Europe or the USA. But we have to be
aware of educational demographics - for instance, illiteracy can be up to
40% in some microbicide trial sites. So visual aids and taped information
helps with informed consent. Events are held on raising awareness,
answering questions, and preparation is done on the social science side
beforehand to ascertain how women access health care in that particular
area, etc. The trial conductors really do know their community, and ensure
that participants understand three key points: that condoms can protect
you from contracting HIV; the gel being used in the trial doesn't
necessarily protect against HIV; and if you become pregnant you must stop
using the gel. Under UK law there is no legal obligation to look at the
ethics of a trial that is taking place outside the UK, but the
Microbicides Development Programme have presented their trial to ethics
boards in the UK.
It is quite
commonplace for vaccine and microbicide researchers to work together. IAVI
and IPM, for instance, are collaborating, as are others.
Informed consent is an
ongoing process, not simply a case of signing a form at the start of a
trial. Prevention tools always need to be put in a social context - IPM
for instance is looking at sexual practices and gel preferences. The
social science agenda develops alongside the trials, and we want to
understand the use of microbicides alongside other prevention products.
Working from an early stage with communities, civil society and
governments is crucial.
In terms of Gates
funding - it is important that this is additional money - it can't mean
that no-one else, such as governments or pharmaceutical companies, funds
the development of new prevention technologies.
Closing remarks by
Deborah Jack, National AIDS Trust Chief Executive
Overall, the
intelligent and challenging questions sum up some of the key challenges we
are facing in developing new prevention technologies. We recognise that
the time-scales are long, but there is no excuse not to do social research
and think at an early stage about how to get these products to
communities. Investment now in new prevention technologies is vital for
developing countries, and for the future for people in Europe and the UK
too.
ALL-PARTY
PARLIAMENTARY 
