Sunday, February 26, 2012
The highly unscientific but quite triumphalist term 'game-changer' appears frequently in the HIV literature. It has appeared in articles about pre-exposure prophylaxis (PrEP) after the iPrEx trial, and also in relation to three mass male circumcision trials. PrEP was said to reduce risk by 44% and circumcision by between 50 and 60%.
However, both of these figures were for relative risk. The respective figures for absolute risk were 2.3% and 1.3%. The term 'show-stopper' might be more appropriate than game-changer. The result of the trial of Tenofovir vaginal gel, also referred to as a game-changer, was said to be 51% effective; but little mention was made of the absolute risk reduction, which was about 5%. (See Joseph Sonnabend's very readable blog on relative and absolute risk.)
Why does this matter? Well, suppose the trial was between a group of people who were given a placebo, forming a control group, and a group of people who were given a herbal dose from the Old Man of Loliondo (look it up if you haven't heard), the second group being the intervention group. The difference between being given a placebo and given one out of many available herbal concoctions should be quite small. HIV incidence in both groups should be roughly the same. But suppose it was lower among those in the intervention group, and that 2 people became infected, compared to 4 in the control group. The absolute risk reduction would be so low that you might decide to spend your 24 Euro Cents for the herbal concoction on something else (though certainly not circumcision, PrEP or vaginal gel, which are at least hundreds of times more expensive).
I apologise to the Old Man and his acolytes, but he can take comfort in the fact that his concoction might easily reduce HIV infection risk as much as circumcision, PrEP or vaginal gel do. Indeed, it might even exceed their rather puny results, who knows? The relative risk reduction in the above example would be 50%. And if people were told that, they might think the Old Man is worth a visit. But they would be wrong. Even if the absolute risk reduction were a lot higher, people would be better advised to use condoms, much as they are when it comes to circumcision, PrEP and vaginal gel.
There have been numerous articles about how happy men and women are with circumcision programs, many of which have already been running for three or four years and claim to have operated on several million men to date. But there is also a recent article in a Zimbabwean paper questioning circumcision, even referring to it as a 'dangerous distraction'. In fact, the article uses the absolute risk reduction figure, so it's not surprising they question the wisdom of circumcising millions of men. It's just disappointing that more articles don't use this figure, or both figures, and question the exuberant press releases a bit more closely.
Apparently it was estimated that 750,000 HIV infections could be averted if 80% of adult males were circumcised. But this figure now seems difficult to support, especially as incidence is already dropping in some groups in Zimbabwe and in many other sub-Saharan African countries and has been for quite a few years. Gregory J. Boyle and Gregory Hill have specifically pointed out how the superficially impressive 60% relative risk reduction needs to be compared to the 1.3% absolute risk reduction. Hopefully, people will use these figures to make up their own minds before being railroaded into being circumcised or into persuading their partner or relatives to be circumcised. They also raise the rather embarassing fact that in quite a number of African countries, HIV rates are higher among circumcised people than uncircumcised people.
It's great that these questions are being asked, in an academic paper and in a newspaper. But none of the serious objections to circumcision, PrEP or vaginal gel are new to those carrying out research in these areas. There appears to be a cabal of HIV 'experts' who are doing everything they can to persuade people of the effectiveness of various public health interventions by selectively publishing favorable data and suppressing or giving far less attention to less favorable data.
[For more about non-sexual risks for HIV transmission, see the Don't Get Stuck With HIV site and blog.]