Not wanting to be always the purveyor of bad news, I was looking forward to today’s results from the Pro2000 microbicide studies. After hopeful results in an earlier trial, I’d convinced myself the gel would prevent HIV. But it doesn’t.
It’s very depressing news from a huge, well designed and well managed study of over 9,000 women across four countries. I’m fond of saying that if you torture the statistics enough they will confess to anything (as we saw in the recent vaccine trial in northern Thailand.) But however badly you twist the arms of this study, they’re not going to scream success. For the record:
* If you exclude the women who got pregnant or stayed in the trial more than the planned period of one year, there were 130 new infections among those who used the microbicide gel, and 123 in those who used the identical-feeling placebo. Calculated as new infections per 100 woman-years of exposure, that’s 4.5 for the gel and 4.3 for the placebo, making the microbicide 5% more risky. The statisticians are 95% sure that the true effect of the microbicide is somewhere between decreasing risk by18 % or increasing it by 34 %. In other words, we can’t make any claims at all that the product works.
* If you don’t exclude people who got pregnant and look at everyone in the trial for as long as they were enrolled, you get 145 new infections with the microbicide versus 143 without: 4.6 new infections per 100 years of exposure in both. No difference. None. The true effect using this analysis is somewhere between reducing the risk of HIV infection by 21% and increasing it by 26%.
* The researchers also looked at whether women who used the gel consistently were less likely to get infected than those who didn’t. They weren’t.
It is hard to measure consistent use of microbicides in these studies, but researchers compared three sources of information: what all participants reported during study visits, whether all participants brought back used applicators, and what a sub-sample of women recorded in their detailed sex diaries. All point in the same direction: around 90% of women used the gel most of the time. That in itself might be counted a triumph compared to some earlier studies. It means that if we could find something that actually works, women would be quite likely to want to use it. All eyes will now be on the CAPRISA study which is testing a vaginal gel that has antiretorvirals embedded in it.
For my own part, I’m feeling somewhat sheepish as well as disappointed. When the results of an earlier, smaller trial of Pro2000 microbicide showed that it reduced infection by 30%, I was dismissive, bordering on rude, about the tyranny of the statisticians who said the results were “not significant”, and that we needed more research before acting.
I remain impatient with scientists who want to delay any action until we have perfect data. In the field of public health we are often obliged to do the best we can with what we have; as long as policy-makers are prepared to change their approach as the data improve we can save valuable time and lives. But in this case, the caution was well placed. Mea culpa.
Once again, it is worth drawing attention to the most basic fact in this research: 30 years into the epidemic, in a population that had safe sex counselling up the wazoo as well as universal access to condoms and other services such as STI treatment, more than four in 100 women are still getting infected with HIV. Pro2000 may not work, but just urging people to use condoms doesn’t, either. We need to keep looking for something that does.