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,
AVAC
