GLOBAL: Straight Talk with Dr Zeda Rosenberg, CEO of the International Partnership for Microbicides
Dr Zeda Rosenberg, CEO of the International Partnership for
Johannesburg, 12 August 2010 (IRIN) - There were cheers and some tears at the International AIDS Conference in Vienna in July when delegates heard the news that a clinical trial
in South Africa, had found a vaginal gel containing the antiretroviral drug, tenofovir, was 39 percent effective at reducing women's risk of contracting HIV during sex.
"There were tears from many people – tears of happiness that finally there is something we can work towards - and a lot of tears of sadness for all of the women whose lives have been lost waiting for a microbicide," Dr Zeda Rosenberg recalled at a recent meeting in Johannesburg, South Africa, hosted by the International Partnership for Microbicides (IPM
), a non-profit organization.
IPM is involved in coordinating and funding the long process of developing effective microbicides - products that women can apply vaginally to protect themselves against HIV - and making sure they reach the women in developing countries who most need them. Rosenberg, who has been working in the field of HIV prevention research for more than two decades and is CEO of IPM, talked to IRIN/PlusNews after the meeting.
What do you think is the likelihood that women will use a microbicide any more consistently than men use condoms?
Part of the issue with condoms is that although they're highly effective, many people put a large value on skin-to-skin contact and ... in long-term relationships it just seems that condoms aren't used as often because it's a trust issue, an issue of intimacy; and also, if everyone uses a condom all the time, women can't get pregnant.
So there really does need to be a method that women can use where they and their partners don't feel it reduces intimacy, allows for conception, and is culturally acceptable.
I think microbicides need to be marketed with the message: 'Condoms should be used', because you don't want a less effective microbicide replacing highly effective condoms. At some point there will be all of these partially effective methods that, when used together, will be highly effective.
Adherence was a challenge in the [South African] trial - those women who reported greater adherence had greater efficacy. [The investigators] also saw a drop-off in product use over the course of the study, which means you need something that's sustainable in the long term.
What level of efficacy would you need before you could take a product to a regulatory authority and start seeking approval?
It just has to be statistically significant - there's no magic number. That really has to do with the regulatory authority's decision on risk benefit. So, if you have a product that's incredibly safe, and there's very little risk, and it has low efficacy, from a regulatory perspective they may find that that is fine.
But ... it depends where the drug is going to be used. Because there isn't a high level of HIV incidence in women in the US, they may say, 'We want to see higher efficacy.'
I think there may be arguments when you have an incidence of infection [rate of new HIV infections in a year] in parts of KwaZulu-Natal [the South African province where the trial was run] of 10 percent, that a 40 percent effective product is good enough. That is going to have to be decided by the department of health ... in consultation with civil society groups and regulatory authorities.
Do you think microbicides have a better chance of gaining traction than the female condom?
The female condom doesn't allow skin-to-skin contact, it does not allow pregnancy, there are concerns about its bulkiness sometimes. Again, I don't think it's going to be either or – there will be some women for whom the female condom should be their product of choice [if] that works for them, and then there will need to be other products. I never see this as a trade-off.
Is this product going to be affordable for women in developing countries, and if not, who is going to subsidize it?
Knowing the resource constraints in many of these areas, even something that's considered very inexpensive will still need to be subsidized. It would be important that donors get prepared very quickly to be able to support widespread access to these products.
The tenofovir gel - the applicators are about US$0.50 cents, maybe even less, because none of these prices have been determined on a mass marketing scale ... the plastic applicator actually costs more than the drug, [which] is very inexpensive.
... are anywhere between $4 and $6, and that's something you would use for a month. Clearly, anything that extends the duration of use will end up being much cheaper over the long haul.
What about the [drug-]resistance issue? What if a woman who doesn't know she's HIV positive uses an ARV-based microbicide?
No one knows; those studies have not been done because no one would want to do that kind of a study unless you know the product was highly effective and it was worth that risk.
In the course of the trial [by the Centre for the AIDS Programme of Research in South Africa (CAPRISA)] ... none of the women who became infected acquired a resistant strain of the virus. So, at least in the context of monthly testing, it was safe. What we don't know is what would happen out in the real world if testing was less frequent - and those studies are going to have to be done.
Do you think there is a more ethical way of conducting microbicide trials, which doesn't rely on the fact that a certain percentage of participants will become infected?
I think the trials are done very well in terms of the informed-consent process, making sure that they're as at low a risk of infection as possible, with good condom counselling, and treatment of sexually transmitted diseases.
It's incumbent upon the trial sponsors to make sure the women have as low a risk of infection as possible, even though the only way to know if something works is to see whether or not it reduces infection. Ethically that's an obligation, and everyone takes it very seriously; in fact, it becomes heart-breaking when women are diagnosed [HIV positive] during a trial.
When a product is licensed for use, then the discussion will be about comparing [a candidate microbicide] to an active control [a product with proven efficacy] because then there will be no placebo control; it means the trials [will have to] get bigger.
How much longer will women have to wait before they get to use an effective microbicide?
Everything depends on the Medicines Control Council (South Africa's regulatory body) and other regulatory bodies, and what they want to see. In general, there would need to be a confirmatory study.
There is a study that's already in the field [the Vaginal and Oral Interventions to Control the Epidemic (VOICE
) trial]. That ends in 2013 and it takes a little while for regulatory approval, say, a year. So ... if everything goes well, you could be looking at four to five years, and that assumes confirmation.