Microbicides 2004 was a rare event for London: a global HIV scientific meeting. But this conference, attracting 800 people from 53 countries, was unusual in many other ways too. Julian Meldrum reports
 image courtesy of microbicides 2004 |
Microbicide meetings are different from any other HIV event. It’s the women: intelligent, forceful, committed women, who form a majority of delegates. Women, like veteran HIV activist Robin Gorna, adviser to the UK’s Department for International Development, and Dr Geeta Rao Gupta, president of the International Center for Research on Women in Washington, DC. Thanks to these women and others like them, every session, workshop and coffee break was infused with an infectious passion to find better methods under women’s control to stop the spread of HIV.
Even government ministers Hilary Benn and Gareth Thomas of the Department for International Development, not to mention HRH the Princess Royal, caught the bug. It helps that microbicide research is an area where UK-based scientists are pioneers. A lifetime achievement award presented by Princess Anne to microbicides pioneer Dr Alan Stone was a fitting recognition of this leadership.
There was fun to be had listening to reports by journalists who had clearly never heard the word before and who struggled with pronunciation. Repeat slowly, after me, mike - robe - iss - ide.
Positive men and women, have been involved as volunteers in safety studies. This is wise, as microbicides can have no impact unless people living with HIV are exposed to them. There could be a direct benefit if microbicides can block transmission of infections other than HIV, or of HIV to our partners. There may also be a chance of stopping re-infection with HIV, which can worsen the course of illness or hinder treatment.
 Women were out in force at the conference. Delegates at the opening reception. photo: ©astonleigh studio/microbicides 2004 |
In the short term, microbicide research requires many women in communities heavily affected by HIV to volunteer for confidential HIV counselling and testing. In the process, many are discovering, often unexpectedly, that they are HIV positive. These women need immediate support and access to services. Active community involvement throughout trials, including positive people, is vital for microbicide research to proceed without harming the communities where it takes place.
There was a very public debate about the principles that should underpin the standard of care delivered in microbicide trials, to those excluded as well as to participants. In all honesty, it didn’t feel like much of a debate. Everyone agrees; access to treatment and care must expand as fast as possible. Similarly, HIV prevention has to improve for treatment programmes to be sustainable over time, even in the wealthiest countries.
This year is the start of a new phase in the global effort to develop microbicides. No fewer than six different gels are set to enter full-scale clinical trials across a number of African countries and in India, to see if any can protect HIV negative women from HIV. With determined efforts from trial staff and thousands of volunteers, results should be available by 2007.
 Robin Gorna of DfID photo: ©astonleigh studio/microbicides 2004 |
If any product is even moderately effective, the field will receive an immense boost. The pharmaceutical industry, which until recently showed little interest in developing these products, can also be expected to invest significant amounts in the field. If they fail, there are at least 60 more potential products in the pipeline.
Public investment is increasing, with backing from the US government’s Aids research budgets and from the European Union. There is also promise of additional funding from the UK’s Department for International Development, the Bill and Melinda Gates Foundation and others concerned with global public health.
At least two serious alternatives to protect women from HIV were outlined during the conference, which could each deliver results as rapidly as the main drive to test new microbicides.
In India, local pharmaceutical companies have teamed up with the Seattle-based Program for Alternative Technologies in Health, backed by the Bill and Melinda Gates Foundation, to evaluate vaginal products already on the market as potential microbicides. They have already identified an antifungal drug, cicloproxolamine, which is active against HIV in lab tests. They now plan to test it against common infections and promote its use for vaginal hygiene.
 Dr Geeta Rao Gupta. photo: ©astonleigh studio/microbicides 2004 |
A completely different approach, described by an American researcher, Dr Preston Marx, stems from research on the influence of hormones on virus transmission. In female monkeys, progesterone makes them susceptible to HIV-type viruses, and oestrogen protects against vaginal exposure. The relevance of these studies to women has increased with recent findings that women who use Depo Provera (a long-acting form of progesterone) for contraception are at greater risk of HIV infection than equally HIV-exposed women who do not.
A vaginal cream already on the market for treating symptoms of the menopause, containing a mild natural hormone called estriol, is able to block virus transmission in female monkeys, when applied twice a week. The monkeys could still be infected when the virus was injected through their vaginal mucosa, so the protection must have been due to changes in the vagina itself. These changes also limit uptake of the hormone into the monkeys’ bodies, limiting side effects. The changes last at least two weeks after treatment stops.
It is unknown what effects this cream would have on younger women, so extended safety studies on monkeys are now under way. It might be contraceptive, suggesting it could be offered to women taking Depo Provera to see if it reverses their increased risk of HIV and other sexually transmitted infections. If the cream works well and has limited and reversible side effects, tests in other groups of women could follow quickly.
Men could have the option of penile wipes to use after sex, to reduce their exposure to a range of sexually transmitted infections. Prototypes seem to have been surprisingly acceptable when tested in Malawi and Kenya. Unfortunately, the particular chemicals used seem to have worrying effects in mice, increasing the animals’ susceptibility to viral diseases. This idea should perhaps wait until better products are available.
Many gay men and the many heterosexuals who engage in anal sex could benefit
from the development of rectal microbicides. These are a bigger challenge
than vaginal microbicides because the area to be protected, when receiving
anal
sex, is much larger and more vulnerable to the virus. This research is
not easy, but it is already producing some of the methods that will be
needed
to evaluate potential products for safety and effectiveness. Spectacular
high-tech
images in a presentation by Dr Craig Hendrix of a ‘semen surrogate’ spreading
inside a volunteer, reaching as high as his spleen, show the scale of the challenge.
Newer microbicides in the pipeline include several based on antiretroviral
drugs. In principle, these seem more likely to have the properties needed
for a rectal microbicide than current leading candidates. Some are also
well suited
to slow-release formulation in a silicone ring, which could be placed in
the vagina and left there for months at a time. Although a form of tenofovir
is
in clinical trials, most of these drugs are non-nucleoside reverse transcriptase
inhibitors (NNRTIs). In theory, these should be better as microbicides
because they are active ‘as is’ while tenofovir must enter a cell to take
its active form. The best are ‘tight-binding’ agents which
can disable the virus inside or outside a human cell, and have effects
that last
for several days.
The two most advanced NNRTI microbicides are UC-781 licensed to Biosyn Inc, and TMC-120, developed as a treatment drug by Tibotec, a Belgian company owned by US giant Johnson & Johnson. Both drugs are poorly absorbed, putting paid to them as orally dosed HIV treatments. However, in microbicides this could be an advantage, limiting the risks of side effects and drug resistance. TMC-120 is licensed, free of charge, to a not-for-profit organisation: the International Partnership for Microbicides (IPM), which has the right to test and market the product in developing countries. Johnson & Johnson would license the product back from IPM, at a price, for sales in wealthier countries. Finding positive volunteers willing to test the product to make sure that it does not generate drug-resistant virus may be an early challenge.
