Tuesday, October 14, 2008

Cutting through the news

Understanding recent reports on male circumcision

October 14, 2008

Dear Advocates,

The past two weeks have brought a flurry of news stories and scientific publications about male circumcision for HIV prevention. The latest wave of coverage and information includes more on what's known--and what remains unknown--about the relationship between circumcision status and risk of HIV infection in gay men and other men who have sex with men (MSM). Additional news coverage included country-level reporting from sub-Saharan Africa. This Advocates' Network update explores what the new data mean, and underscores some of the key advocacy messages and challenges around male circumcision for HIV prevention.

In the October 8, 2008 issue of the Journal of the American Medical Association (JAMA), the CDC's Greg Millett and co-authors published a meta-analysis of 15 quantitative studies that gathered data on the association between male circumcision and rates of HIV infection and sexually transmitted infections among gay men and other MSM. Meta-analysis is the term used for a statistical review of a wide range of studies conducted on a given topic. Researchers collect existing studies and quantitatively aggregate the data--which means that the data are combined and analyzed together. A meta-analysis is used to get an overall picture of the conclusions that can be drawn from many different studies.

One of the reasons that Millett and his colleagues looked at the existing literature on gay men and other MSM and male circumcision is because of outstanding questions about whether circumcision confers any protection during anal sex. There have been randomized controlled trials looking at male circumcision during vaginal sex, and these have shown a significant reduction in men's risk of acquiring HIV. Randomized controlled trials are considered the "gold standard" of scientific study in that, when well-designed and -conducted, they can generate clear and relatively conclusive answers. There have been no randomized controlled trials of male circumcision and HIV risk in the context of homosexual or heterosexual anal sex.

As Millett and his co-authors reported, the meta-analysis of 15 studies did not find evidence that circumcision significantly reduced men's risk of acquiring HIV during penile-anal homosexual sex. However, looking across the studies, the authors did find that the odds of being HIV-positive were 14 percent lower in men who were circumcised compared to men who were not circumcised.

This gap was not statistically significant, meaning that the data don't support a firm conclusion about circumcision lowering HIV risk in gay men and other MSM. This is the conclusion that was picked up and quoted most frequently in the media coverage that followed. But it is important to note that this is not the only message from the meta-analysis, and that this conclusion does not settle the question of whether male circumcision can play a role in reducing the risk of HIV infection in gay men and other MSM.

The meta-analysis yielded some other intriguing findings as well. For example, the authors looked at the results from studies before and after the introduction of highly-active antiretroviral therapy (HAART). In the pre-HAART era, men who were circumcised were significantly less likely to have HIV compared to men who were not. Once HAART was introduced, this gap disappeared. It's not clear why this might be, and while the authors suggest that it might be due to changes in risk behavior post-HAART, it's not possible to confirm that theory based on these data.

The authors also looked at the methodological quality of the studies reviewed in the meta-analysis using various criteria. In the subset of studies with the highest methodological quality, male circumcision was associated with protection from HIV infection, although here, too, the effect was not statistically significant. Based on this and other elements of evidence from the meta-analysis, the authors conclude by stating that there are still valid questions about benefit of male circumcision as a risk reduction tool for gay men and other MSM, and that a further study is warranted.

Sten Vermund and Han-Zhu Qian of Vanderbilt University in a JAMA editorial that accompanied the study, take up the questions that Millet and colleagues raised about how best to gather additional evidence on male circumcision for HIV prevention in gay men and other MSM. There are significant methodological challenges to undertaking a randomized clinical trial in gay men and other MSM. Both JAMA pieces argue that such a trial would need to recruit men practicing primarily insertive sex, since circumcision status wouldn't affect risk in men practicing primarily receptive sex.

The authors suggest additional elements of a research agenda to learn more about circumcision and anal sex between men. Millett and colleagues suggest studies that gather information about how many gay men and other men who have sex with men practice insertive or receptive sex, or are "versatile," and how these behaviors and/or identities relate to race, ethnicity, age, geography, culture or other factors. That such basic information does not currently exist for the vast majority of communities of gay men and other men who have sex with men is a reminder of the gaps in research funding and priorities for MSM around the world.

The authors also suggested studies of HIV risk behaviors in uncircumcised and circumcised men that explore how these behaviors relate to HIV status. Also recommended is research comparing the relative effectiveness of HIV prevention strategies, such as behavioral interventions, with mathematical models of male circumcision and HIV infection among gay men and other MSM. Lastly, research is needed to determine the differences in viral shedding that exist in the vagina compared to the anus, and how potential differences in viral load in either opening may affect transmission.

Want to learn more? All advocates are invited to join the discussion "Fact Check: Taking a Cut for HIV Prevention--Would Scale Up of Male Circumcision Reduce HIV Incidence in the US?" The CDC's Greg Millett will present, and CHAMP will host the call, Wednesday, October 15, 3:30-5:30 EST, Dial in: 866-740-1260, pass code 4272302#.

The relationship between male circumcision and HIV risk in MSM will almost certainly receive increased attention as discussions of the proposed HVTN 505 vaccine trial proceed. Negotiations about whether and how the US NIH's Vaccine Research Center's DNA-Ad5 prime-boost strategy will go forward are in early stages, and the protocol is still being drafted. However, we already know that the study will be restricted to circumcised MSM with no previous exposure to the adenovirus, because there was no increased susceptibility to HIV in this group in the predecessor STEP vaccine study. (For background on the STEP study visit www.avac.org/step.htm).

The ongoing open questions about male circumcision among MSM should not confuse the potential utility of male circumcision for reducing heterosexual men's risk of HIV infection during vaginal sex. This is the argument that was made in a letter to the editor, "Male circumcision is an efficacious, lasting and cost-effective strategy for combating HIV in high-prevalence AIDS epidemics," authored by numerous leading international HIV experts, and published in Future Medicine, September 2008.

The article is an attempt to debunk a prior paper, "Male circumcision is not the 'vaccine' we have been waiting for!" previously appearing in the same journal. In sum, the advocates for male circumcision as HIV prevention state that "there is overwhelming scientific evidence of the efficacy of male circumcision for HIV prevention. Given the urgent need to confront the AIDS epidemic in some parts of Africa...several ethical analyses have concluded that it is unethical not to offer heterosexual men at risk of exposure to HIV infection access to safe, voluntary circumcision services."

In addition to these recent journal articles, there have also been a number of media articles about scaling-up male circumcision programs in South Africa and Uganda, amongst other countries.

With many questions to address, there are also some core advocacy messages that remain essential:

  • Male circumcision has the potential to be a powerful tool for reducing men's risk of HIV infection during vaginal sex.
  • The potential benefits of male circumcision for HIV prevention will be optimized in programs that include male circumcision as one component of an overall prevention strategy that also includes behavior change messages, couples counseling where possible, HIV testing and counseling services, provision of male and female condoms, and clear counseling messages about the risk involved in resuming sex before six weeks after surgery. (Early resumption of sex before wound healing puts HIV-negative men and the women partners of HIV-positive men at higher risk of infection during the immediate post-surgery period.)
  • Rollout of male circumcision programs must address the broader implications for women including its impact on men's willingness to use condoms, numbers of partners, and shared sexual decision-making. Additional issues include how rollout of male circumcision will affect spending allocations for women-focused HIV prevention, and stigma and blame directed at HIV-positive women. (For more information about male circumcision and women, click here)
  • Further research is indeed warranted to evaluate the effect of circumcision on HIV incidence in MSM, because this population continues to be disproportionately over-represented in new HIV infection rates.
  • For more information on medical male circumcision in heterosexual men, click here.

As always, we invite you to contribute to this ongoing discussion. Please share your comments, questions and suggestions for moving this work forward by emailing us at avac@avac.org.

Best regards,


1 comment:

Hugh Young said...

There's big gap in the studies of circumcision and HIV transmission. What effect does the insertive partner's circumcision status have on the risk to the receptive partner? Nobody seems to be looking at this, whether the receptive partner is male or female, yet it seems highly likely that 1) the intertive partner's hardened (keratinised) glans is more likely to create exactly the kind of micro-tears in the receptive partner's rectum (or vagina) that facilitate the transmission of HIV to that partner, and 2) there is ample anecdotal evidence (and it is clearly visible by comparing US vs European porn) that circumcised men thrust more violently (because they are missing some 10,000 fine-touch sensitive nerves) in order to achieve their goal.

The "numerous leading international AIDS experts" (Halperin et al.) who answer Green's paper "Male circumcision is not the 'vaccine' we have been waiting for" include all the same researchers who first made a noise about the wonders of circumcision, carried out the studies, multiplied their results by the population of Africa to “prove” that “millions could be saved”, did other studies to show it has no effect on sex* or behaviour, run clinics to circumcise Africans, and now run to the media to say how good circumcision is.

* That study found virtually all the men enjoyed almost perfect sex, circumcised or not. How very different from the rest of us, and every other study. The women weren't asked.

Their rebuttal falls short of convincing. For example, one of its references for "ethics" is a grab-bag article (by a well-known circumcision enthusiast) of reasons to circumcise for any and all reasons, including zipper injury and "bathroom splatter", that does not contain the word "ethics", and dismisses "human rights" with scornful quotation marks.

Halperin et al. fail to answer Green's objection that the dropouts in the three Random Controlled Trials outnumbered the known HIV seroconversions by several times, by begging the question that they were a random sample of participants, when clearly, finding you were circumcised and HIV+ would be more likely to disillusion you with the trial than other outcomes.

Daniel Halperin is on record as thinking his descent from a ritual circumcisor meant “maybe in some small way I’m ‘destined’ to help pass along [circumcision] to people in [other] parts of the world … .” (Cover Story: The Case for Circumcision. By Gordy Slack. The East Bay Express Online. May 19-24, 2000.) Whatever else that it, it’s not science.

New studies by different researchers with different protocols would be more convincing.

There are several unaddressed risks to male circumcision, even when voluntary (and the enthusiasts are happy to do it to the nonconsenting): it does nothing to protect women, though it can disempower them against refusing unprotected sex; it may give men a false sense of security; desensitisation may make them less willing to use condoms; risks of the surgery itself, including HIV transmission from dirty instruments; risk of increased HIV transmisssion if the men resume sex before their wound has properly healed. The experimenters seem happy to neglect these risks, even declaring it is "safe" to circumcise HIV+ men, though this will do nothing to protect anyone.

For some reason, the idea of circumcision makes people lose their critical faculties. There has been far too little criticism of the lemming-like rush to circumcise, instead of using means that are known to work.

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