A fatal irony: Why the “circumcision solution” to the AIDS epidemic in Africa may increase transmission of HIV
A fatal irony: Why the “circumcision solution” to the AIDS epidemic in Africa may increase transmission of HIV
1. Experimental doubts
A handful of circumcision advocates have recently begun haranguing the global health community to adopt widespread foreskin-removal as a way to fight AIDS. Their recommendations follow the publication of three  randomized controlled trials (RCTs) conducted in Africa between 2005 and 2007.
These studies have generated a lot of media attention. In part this is because they claim to show that circumcision reduces HIV transmission by about 60%, a figure that (interpreted out of context) is ripe for misunderstanding, as we’ll see. Nevertheless, as one editorial  concluded: “The proven efficacy of MC [male circumcision] and its high cost-effectiveness in the face of a persistent heterosexual HIV epidemic argues overwhelmingly for its immediate and rapid adoption.”
Well, hold your horses. The “randomized controlled trials” upon which these recommendations are based are not without their flaws. Their data have been harnessed to support public health recommendations on a massive scale whose implementation, it has been argued, may have the opposite of the claimed effect, with fatal consequences. As Gregory Boyle and George Hill explain in their extensive analysis of the RCTs:
While the “gold standard” for medical trials is the randomised, double-blind, placebo-controlled trial, the African trials suffered [a number of serious problems] including problematic randomisation and selection bias, inadequate blinding, lack of placebo-control (male circumcision could not be concealed), inadequate equipoise, experimenter bias, attrition (673 drop-outs in female-to-male trials), not investigating male circumcision as a vector for HIV transmission, not investigating non-sexual HIV transmission, as well as lead-time bias, supportive bias (circumcised men received additional counselling sessions), participant expectation bias, and time-out discrepancy (restraint from sexual activity only by circumcised men).
That’s a whole laundry list of issues, so let me highlight a few of the more substantial. First, consider the “lack of placebo control.” What does that mean? Normally, when you’re trying to determine whether some medical intervention has a disease-fighting effect specific to its own (hypothesized) mechanisms—and over and above the placebo baseline—you have to have a control group. That group gets a dummy intervention, and nobody is supposed to know which participants were exposed to the actual treatment until after the results are in.
After all, if someone knows (or thinks) that they’re getting a great big helping of medicine, they might act in various ways—whether consciously or unconsciously—that have the effect of generating positive health outcomes but which have nothing to do with the intervention itself. In the case of circumcision, however, there’s no way not to know if you’ve received the “medicine”—you have to go through a surgery and then you don’t have a foreskin anymore—so this basic condition of a true clinical trial is violated in the first instance.
But that’s just the tip of the iceberg. As Boyle and Hill point out, the men who were circumcised got additional counseling about safe sex practices compared to the control group, and then they had to refrain from having sex altogether for the simple reason that their lacerated penises had to be wrapped in bandages until their wounds healed – leading to what Boyle and Hill refer to as “time-out discrepancy” in the quote above. By contrast, the non-circumcised men got to keep having sex during the full two month period during which the treatment group was in recovery mode. Then (due to a statistically significant effect having been detected) the trials were stopped early — which tends to lead to an overestimation the true effect size of the treatment. These issues may pose problems for the scientific credibility of the studies. Taken together with the other flaws, here is why:
Let us assume for a second that the circumcised men really did end up getting infected with HIV at a lower rate than the control-group men who were left intact—even though, as we will see in a moment, it would be premature to be convinced that this is so. Why might that outcome have happened?
If you answered, “Because those men knew they were in the treatment group in the first place, had less sex over the duration of the study (because they had bandaged, wounded penises for much of it), and had safer sex when they had it (because they received free condoms and special counseling from the doctors), thereby reducing their overall exposure to HIV compared to the control group” then you are on the right track.
2. Misleading results
Experimental design issues notwithstanding, it is tempting to think that the 60% figure that’s being thrown around in media reports is just too large a percentage to ignore–even if the studies had some flaws. But do you know what the “60%” statistic is actually referring to? Boyle and Hill explain:
What does the frequently cited “60% relative reduction” in HIV infections actually mean? Across all three female-to-male trials, of the 5,411 men subjected to male circumcision, 64 (1.18%) became HIV-positive. Among the 5,497 controls, 137 (2.49%) became HIV-positive, so the absolute decrease in HIV infection was only 1.31%.
That’s right: 60% is the relative reduction in infection rates, comparing two very small percentages: a bit of arithmetic that generates a big-seeming number, yet one which–without also reporting the absolute risk reduction alongside–arguably misrepresents the results of the study. The absolute decrease in HIV infection between the treatment and control groups in these experiments was just 1.31%, which is likely to have no appreciable effect at the demographic level.
3. Questionable public health recommendations
So far we have been discussing problems with the experiments themselves—what’s called “internal validity” in technical terms. I really want you to read the Boyle and Hill paper here, because they go into painstaking detail about each of a long parade of flaws I can’t hope to cover in one blog post. But let’s switch gears now and talk about the flip-side of things, or what’s called “external validity” – that is, problems with taking what you’ve (supposedly) found in a (relatively) controlled setting like an experiment and applying it to the chaotic mess that is the real world.
Lawrence Green and his colleagues published an important article on just this topic as it relates to “the circumcision solution” in the American Journal of Preventative Medicine. “Effectiveness in real-world settings,” they sensibly point out, “rarely achieves the efficacy levels found in controlled trials, making predictions of subsequent cost-effectiveness and population-health benefits less reliable.”
Some major issues with trying to roll-out circumcision in particular include the fact that the RCT participants—who were not representative of the general population to begin with—had (1) continuous counseling and yearlong medical care, as well as (2) frequent monitoring for infection, and (3) surgeries performed in highly sanitary conditions by trained, Western doctors. All of which would be difficult to replicate at a larger scale in the parts of the world suffering from the worst of the AIDS epidemic. So what should we conclude? Green et al. get it right: “Before circumcising millions of men in regions with high prevalences of HIV infection, it is important to consider alternatives. A comparison of male circumcision to condom use concluded that supplying free condoms is 95 times more cost effective.”
Not only more cost effective, of course but also more effective—period—in slowing the spread of HIV. Condoms are cheap, easy to distribute, do not require the surgical removal of healthy genital tissue, and—yes—are much more effective at preventing infections. Compare. Condoms: 80% minimum reduction in HIV infection, for both males and females . Circumcision: 60% relative risk reduction (and 1.3% absolute reduction), of female-to-male transmission only, according to the most optimistic presentation of data from three contested studies. Of course, one could reasonably argue that men with a high risk HIV infection could use both strategies to boost their protection–wearing condoms and getting circumcised–but the threat of behavioral disinhibition makes this argument a bit more tricky than it appears at first. I explain why in the following section.
4. This is serious business
The most troubling part about all of this is not just that the science behind “the circumcision solution” is being promoted with so little caution or debate, but that the actual implementation of these recommendations may very well lead to more HIV infections, not less. The big idea here is “risk compensation” – the subject of an interesting paper by Robert Van Howe and Michelle Storms.
Risk compensation occurs when people believe they have been provided additional protection (wearing safety belts) [such that] they will engage in higher risk behavior (driving faster). As a consequence of the increase in higher risk behavior, the number of targeted events (traffic fatalities) either remains unchanged or [actually] increases.
Risk compensation will accompany the circumcision solution in Africa. Circumcision has been promoted as a natural condom, and African men have reported having undergone circumcision in order not to have to continually use condoms. Such a message has been adopted by public health researchers. A recent South African study assessing determinants of demand for circumcision listed “It means that men don’t have [to] use a condom” as a circumcision advantage in the materials they presented to the men they surveyed. [Yet] if circumcision results in lower condom use, the number of HIV infections will increase. [Citations can be found in the original paper.]
In Uganda, as Boyle and Hill uncovered, the Kampala Monitor reported men as saying, “I have heard that if you get circumcised, you cannot catch HIV/AIDS. I don’t have to use a condom.” Commenting on this problem, a Brazilian Health Ministry official stated: “[T]he WHO [World Health Organization] and UN HIV/AIDS program … gives a message of false protection because men might think that being circumcised means that they can have sex without condoms without any risk, which is untrue.”
Van Howe and Storms spell this all out:
How rational is it to tell men that they must be circumcised to prevent HIV, but after circumcision they still need to use a condom to be protected from sexually transmitted HIV? Condoms provide near complete protection, so why would additional protection be needed? It is not hard to see that circumcision is either inadequate (otherwise there would be no need for the continued use of condoms) or redundant (as condoms provide nearly complete protection).
The argument that men don’t want to use condoms needs to be addressed with more attractive condom options and further education: [they need to be told] that sex without a condom and without a foreskin is potentially fatal, while sex with a condom and a foreskin is safe. No nuance is needed. Offering less effective alternatives can only lead to higher rates of infection.
Rather than wasting resources on circumcision, which is less effective, more expensive, and more invasive, focusing on iatrogenic sources and secondary prevention should be the priority, since it provides the most impact for the resources expended.
That is my conclusion as well. In this article I have focused on just the science behind—and claimed public health benefits of—“the circumcision solution” and shown how contentious they are. I’ve completely ignored the attendant ethical issues, though I discuss these elsewhere.
The studies we’ve looked at, claiming to show a benefit of circumcision in reducing female-to-male heterosexual transmission of HIV, are a lot less bulletproof than their proponents make out; and any real-world roll-out of their procedures would be very difficult to achieve safely and effectively. One possible outcome is that HIV infections would actually increase—both through the circumcision surgeries themselves performed in unsanitary conditions, and through the mechanism of risk compensation and other complicating factors of real life. The “circumcision solution” is no solution at all. It is a misdirection of resources and may be a threat to public health.
NOTE: UPDATE AS OF MARCH 4, 2014: Please note that the paper by Boyle and Hill, of which this post was meant to be a reader-friendly summary, has been critiqued by Wamai, Morris, and Waskett et al., in a paper published subsequently in the same journal. I encourage readers to take a look at the critique published by these authors, so that they can evaluate the arguments going back and forth between opponents and proponents of (adult) male circumcision. I would note that both Morris and Waskett (the second and third authors of the critique) have been recently criticized (here and here) for misrepresenting the scientific literature on circumcision (which is a similar claim they raise against Boyle and Hill) so this is a contentious area indeed. Please also see this critique of my post by Nathan Geffen, to whom I am most grateful for drawing my attention to various counter-arguments that have been raised against the contentions of Boyle & Hill. If readers are aware of any cogent replies to these counter-arguments that I should take note of, please do let me know.
WORKS REFERENCED (RECOMMENDED READING):
Boyle, G. J. and Hill, G. (2011). Sub-Saharan African randomised clinical trials into male circumcision and HIV transmission: Methodological, ethical and legal concerns. Journal of Law and Medicine. Available as a PDF here.
Green et al. (2010). Male circumcision and HIV prevention: Insufficient evidence and neglected external validity. American Journal of Preventative Medicine. Available as a PDF here.
Van Howe, R. S. and Storms, M. (2011). How the circumcision solution in Africa will increase HIV infections. Journal of Public Health in Africa. Available as a PDF here.
Darby, R. and Van Howe, R. (2011). Not a surgical vaccine: There is no case for boosting infant male circumcision to combat heterosexual transmission of HIV in Australia. Australian and New Zealand Journal of Public Health. Available here.
Green, L., McAllister, R., Peterson, K., and Travis, J. (2008). Male circumcision is not the HIV “vaccine” we have been waiting for. Future Medicine. Available as a PDF here. A short, readable editorial.
I also recommend Zabus, Chantal (Ed.) (2008). Fearful symmetries: Essays and testimonies around excision and circumcision. Available from Amazon.com here.
 Auvert B, Taljaard D, Lagarde E et al, “Randomized, Controlled Intervention Trial of Male Circumcision for Reduction of HIV Infection Risk: The ANRS 1265 Trial” (2005) 2(11) PLoS Med e298; Bailey RC, Moses S, Parker CB et al, “Male Circumcision for HIV Prevention in Young Men in Kisumu, Kenya: A Randomised Controlled Trial” (2007) 369(9562) Lancet 643; Gray RH, Kigozi G, Serwadda D et al, “Male Circumcision for HIV Prevention in Men in Rakai, Uganda: A Randomised Trial” (2007) 369(9562) Lancet 657.
 Halperin DT, Wamai RG, Weiss HA, et al. Male circumcision is an effıcacious, lasting and cost-effective strategy for combating HIV in high-prevalence heterosexual epidemics: the time has come to stop debating the basic science. Future HIV Ther 2008;2(5):399 – 405.
 Weller SC and Davis-Beaty K, “Condom Effectiveness in Reducing Heterosexual HIV Transmission” (2002) 1 Cochrane Database of Systematic Reviews Art No CD003255.