Crunch Time for Microbicides

posted: 25/05/2010

Professor Robin Shattock, director of the microbicide research at at St George’s Hospital in London, warned the opening session of Microbicides 2010 Conference in Pittsburgh, USA that “we stand at a critical time point in microbicide development. There is a recognised need to prioritise and accelerate efficacy testing in clinical trials,” before funders lose interest in microbicides.
 

Since all the first attempts at non-ARV-based microbicides have failed, there are now just three possible microbicides being studied.
 

Three possible microbicides left
 

• The first is CAPRISA in South Africa, a phase 2b trial of tenofovir gel - expect results in July at the Vienna International AIDS Conference 
• VOICE, a phase 3 trial testing tenofovir gel and tenofovir and tenofovir/FTC PrEP, is recruiting now with results next year. 
• The long-awaited IPM009 trial of dapivirine in a vaginal ring and/or gel is not due to start till 2012.

Microbicides once were the best new hope for prevention, but now what is called ‘pre-exposure prophylaxis’ – giving HIV drugs to people who do not have HIV to prevent HIV infection - is pulling ahead. There are now more ‘pre-exposure prophylaxis’ trials underway or planned than the three trials we have for microbicides.
However, microbicides still look far more hopeful than attempting to make a workable HIV vaccine.
 

Microbicide possibilities
There are now 13 different compounds that might work if used in microbicides being tried out, and more than 20 studies. The compounds that might be used for microbicides range from drugs as familiar as tenofovir, to ones as exotic as nucleocaspid protein inhibitors, and broadly neutralising antibodies. These have all been shown to block HIV infection in monkeys.
 

Next steps – and some of the problems
“Biological plausibility for microbicides has never been stronger,” he said. “But how can this knowledge bridge to better human trials?”

• One problem is making sure any drug reaches the place it needs to, in the right amount, and in a state which will work. We need better ways of measuring these things in people. People are already working on solving this.

Real life practicalities

• An even bigger problem is designing microbicides that will work in the real world. Doctors and researchers usually describe this as an adherence problem – making sure people use the microbicides properly. But if the instructions are unreasonable and don’t fit with real life needs and situations, any unreasonable instructions will be ignored. We learnt that many women simply find it impossible to re-apply a microbicide, when they have sex more than once a night. We learnt this from the Carraguard trial which failed two years ago precisely because this turns out to be a real life requirement.

Professor Shattock told the conference that we need better formulations to maximise adherence. New ways of monitoring adherence would also be needed to measure how well the new microbicides work in real life. Vaginal rings, like those used for contraception, that supply a constant level of drugs, would be one way to overcome this 'adherence' problem.
 

• Microbicides which use a combination of two of three drugs also look a good prospect for investigation.

Money is the key
The challenge now, Shattock told a press conference, is not developing more possible things that might work as a microbicide – there were plenty of those – but finding the money to start trials.
 

Anti-HIV drug microbicides cheaper
You need very little of a HIV drug in a microbicide for it to work – far less than you need when treating someone with HIV. That makes using the same drugs in microbicides relatively cheap compared with the cost of treating someone after infection. A single maraviroc tablet has enough of the drug for up to 20 doses if it is used as a microbicide. “But,” he added, “Without success or even an indication of success soon it will be impossible to sustain the funding for microbicides.”
 

Nono Eland of the South African Treatment Action Campaign, speaking after Shattock, commented that “if we fail on prevention, we will lose the progress we’ve made on treatment,” because funders will be unwilling to provide ever-expanding funding for an uncontainable disease.
 

Waiting women

We seem to have reached a critical moment for the future of microbicides. Microbicides need money now if we are ever to have any that will work. Microbicides are a gender issue. Women's need for an independent form of protection must be taken seriously.
 

Women are still waiting for any type of HIV prevention that will work when men won’t use condoms or it is too risky to suggest this to men. Microbicides are one of the best hopes we have for offering HIV prevention to women.

Source
Shattock R. State of the ART for microbicides. Opening plenary, Microbicides 2010 Conference, Pittsburgh. Presentation #1. 2010.
 

 

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