A recent series of studies in Africa aimed at determining whether circumcision of adult males would reduce their risk for HIV infection has led to a flurry of debate far beyond the borders of the three study host countries: South Africa, Kenya and Uganda. Consistent with other findings internationally, the studies found that men who had been circumcised had a 60 percent (South Africa), 53 percent (Kenya), and 51 percent (Uganda) lower incidence of HIV infection compared with men who were uncircumcised.

These three studies led both the World Health Organization and United Nation’s AIDS Organization – the two largest global agencies that address HIV and AIDS internationally – to issue recommendations that men undergo circumcision to reduce their chances of infection.

The World Health Organization, however, included a caveat in its recommendation, acknowledging that because the studies looked at heterosexual men and, more specifically, female-to-male transmission, further research is needed with regard to the protective benefit of male circumcision in the case of insertive partners engaging in homosexual or hertosexual anal intercourse.

Consequently, it’s important to keep these studies in context, says University of California San Diego Associate Professor of Medicine Dr. Susan Little. “Clearly these studies give us very good data about transmission and risk reduction as it is related to reducing the risk of HIV in men who are circumcised versus those who are uncircumcised,” Little says. “All three demonstrated a 50-60 percent reduction in risk of HIV negative men acquiring HIV. In fact, these were three large trials, in different settings, and three somewhat different age groups. But there is still the issue of whether these studies apply beyond Africa, and, in particular, African heterosexual men.”

Little, like many of her colleagues, accepts without hesitation that the studies were well-conducted, randomized and produced controlled results. In fact, like many of her colleagues, she is impressed by their uniformity in demonstrating that circumcision offers significant protection versus non-circumcision.

“But it is a leap of faith to suggest those studies can be applied to the fight against HIV in the United States,” Little argues.

First and foremost, Little says, all three studies looked at transmission of HIV among heterosexual men when having penile to vaginal sex, not homosexual men or men having sex with men (MSM) where transmission occurs during penile to anal sex. In other words, the study looked at a population of men in which the vast majority of HIV infection of men results from heterosexual encounters, as opposed to a population of men in which a much higher percentage of HIV infection results from homosexual encounters. “Can we assume that these results – a 50-60 percent reduction in HIV transmission – would be replicated in the United States where the predominance [of HIV transmissions] is penile and anal sex?” Little asks. “The answer is no.”

Beyond the fact that the African studies were conducted among heterosexual men, Little points to other reasons why the studies don’t directly corollate to the Western world, and, in particular, the United States.

“There are several subtypes of HIV in African settings, whereas North America and Western Europe have subtype B,” Little argues. “These other subtypes – the ones in Africa – might behave differently.”

There are also vast differences in access to quality health care, Little argues, that may suggest the data does not apply as much to countries such as the U.S., Canada, and those in Western Europe. For example, nearly 80 percent of the U.S. male population is already circumcised, the majority at birth, while, in African nations circumcision rates can be as low as 20 percent, due in part to their large Muslim population. Such differences are red flags indicating that the African studies require further investigation before we apply their findings to the U.S.

Further, while there are a number of biological similarities between vaginal and anal sex there are many differences.

Senior public analyst at the University of California-Los Angeles’ David Geffen School of Medicine Sharif Sawires argues that one of the primary biological issues of HIV transmission when dealing with receptive heterosexual – which is mostly vaginal – and homosexual – which is mostly anal – sexual intercourse is that the surface layers of the anus are considerably thinner than the surface layers of the vagina.

Most reports suggest that 75 to 85 percent of HIV infections globally occur during sexual activity. Most new infections are thought to occur when the HIV virus binds to receptors found in antigen-presenting cells in the genital and rectal mucosa. This includes Langerhans’ cells – found in the foreskin, which has a high density of these target cells. Further, the inner surface, or “inside” of the foreskin has less karetin – a protein substance on the shaft and base of the penis that provides a natural protective barrier from certain viral infections, including HIV.

Consequently, by removing the foreskin, a primary factor in HIV transmission is eliminated. People who have a sexually transmitted infection are two to five times more likely to become infected with HIV, and circumcision is widely considered to be a factor in protecting against sexually transmitted infections such as syphilis and gonnorrhea.

For populations where HIV transmission to men is acquired through unprotected heterosexual contact with women, these are the kinds of biological considerations to take into account. However, in terms of MSMs, it is the receptive partner, not the insertive partner who is most at risk, argue HIV and public health officials in the United States, including Sawires.

“The highest risk for MSM is not to the insertive partner, but to the receptive partner,” Sawires said in a recent article in the Canadian national GLBT newsmagazine Xtra! “MC [Male circumcision] will likely have little or no benefit in transmission rates from insertive to receptive partner, but that is only preliminary. There are a lot of investigators interested in MSM population and MC — so yes, there will likely be a lot of folks looking specifically at the MSM population.”

Kevin Thurgood is an HIV prevention specialist in Northern California.

“There are two big problems with people picking up the paper and reading about the African studies,” Thurgood says. “First, guys who are circumcised are going to think they can have unprotected sex. It’s not that a whole bunch of uncircumcised men are going to go out and get circumcised. No way. It’s that there will be a percent of the population who reads that, assumes that all the HIV infections in the U.S. are mostly uncircumcised guys, and so they can stop using condoms.”

Even more disturbing, though, Thurgood says, is the second group.

“You know, it just may sound crazy, but what I’m saying here is true: there is going to be a percent of the population who believes because they are circumcised, they can have unsafe receptive sex – not insertive, mind you, but receptive sex – and because their penis is circumcised, their body is somehow wired to not be infected.”

Thurgood stresses that, as of yet, no studies have shown that circumcision by itself does anything to prevent the spread of HIV through anal sex or drug injection.

That being said, Thurgood argues, there is still a reasonable argument for circumcision. “If you have someone who is already engaged in high risk behavior and they are uncircumcised, then, yes, going in and getting circumcised is a step in reducing your risk of transmitting HIV,” Thurgood explains. “And since harm-reduction models are really at the forefront of the fight against HIV and AIDS, I would say it is not unreasonable to put it on the list of things people could do if they continue to insist on unprotected sex.”

Beyond the fact that the African studies focused on heterosexual men, researchers in the United States suggest that the results must be viewed with regard to other factors. First, the studies were conducted in resource-poor countries, with significantly lower levels of access to healthcare and significantly higher levels of poverty. Second, there are the issues of culture and education.

“Yes, the studies clearly demonstrate a biological plausibility, but the discussion has to go beyond that,” Little argues. “In the United States, we have to consider race and ethnicity. For example, blacks and Hispanics, groups who, racially, have the lowest rates of circumcision – we have to ask ourselves, ‘Would those groups find it culturally appropriate to circumcise?’ We are also talking about discussions in Africa where the infection rate is 30 to 40 percent of the population, versus countries where the infection rate is one, two, three percent. So, it brings us back to the fact that it is just a different set of questions for the U.S. and Europe than it is for Africa.”

In fact, says San Diego-based pediatrician Dr. Brett Gerber, about 50 percent of parents he sees ever have questions about the risks versus benefits of circumcision.

“Fifty percent of the parents already have in their heads what they are going to do,” Gerber explains. “And it’s very cultural, religious.”

What does Gerber tell those other 50 percent?

“We don’t recommend for or against [circumcision],” Gerber says. “We can discuss the risks and benefits, but we remain unbiased. We leave it up to the parents.”

According to the National Hospital Discharge Survey, 65 percent of newborns in the U.S. were circumcised in 1999, and that number had remained stable for the preceding 20 years. However, the American Academy of Pediatricians shifted its position on circumcision in 1999, from “recommended” to a more neutral stance. Since 1999, 16 states have eliminated Medicaid payments for circumcision that were not deemed medically necessary.

While Gerber says he hasn’t seen a huge decrease in circumcisions since then, Little suggests that because the medical associations have moved to a more neutral stance, circumcision procedures are less likely to be covered by private insurance, and will be classified more as “elective procedures,” meaning patients are less likely to be reimbursed. The logical result is that fewer infants will be circumcised, especially those in high-risk populations.

One of the most frequently asked questions about circumcision is, “What are the potential risks or complications?”

“In infant circumcision, rates range from about .2 to 2 percent for complications,” Gerber explains. “And the complications that we’re talking about are pretty minor. They are pain, infection, swelling, and slight bleeding.”

These are all immediately treatable and pose no major risk to the child, Gerber says.

Obviously, in the regions in Africa where the studies were conducted with 30 to 40 percent of the population being HIV positive, parents may be more open to the medical benefits aspect of the discussion. In the U.S., however, where rates run significantly lower, parents are less likely to think about the long-term benefits of circumcision: cervical cancer reduction, HIV transmission reduction, urinary tract infection reduction, etc.

According to the Centers for Disease Control and Prevention (CDC), a recent study of adult circumcision in adults in South Africa showed complication rates of 3.8 percent, listing the same minor complications as Gerber outlined, with one added complication, “problems with appearance,” which occurred in .6 percent of the population. There were no deaths or problems with urination reported.

There are some cases in which adult circumcision is necessary. These cases, Gerber says, are typically for men whose foreskin is too tight or have some other discomfort caused by the foreskin as the body matures.

Based on the data in the recent studies, will the medical community reverse its decision and recommend circumcision for those born in the U.S.?

The CDC states: “Male circumcision may also have a role for the prevention of HIV transmission in the United States. With the results of three clinical trials showing that male circumcision decreases the risk for HIV infection, CDC is undertaking additional research and consultation to evaluate the potential value, risks, and feasibility of circumcision as an HIV prevention intervention in the U.S. As CDC proceeds with the development of public health recommendations in the U.S., individual men may wish to consider circumcision as an additional HIV prevention measure, but must recognize that circumcision 1) does carry risks and costs that must be considered in addition to potential benefits 2) has only proven effective in reducing the risk of infection through insertive vaginal sex, and 3) confers only partial protection and should be considered only in conjunction with other proven prevention measures (abstinence, mutual monogamy, reducing number of sex partners, and correct and consistent condom use).”

The last point – that circumcision in no way is intended to take place of using condoms and other safer sex methods, cannot be over emphasized.

“People who think because they are circumcised that they won’t become positive are absolutely wrong,” says UCSD Owen Clinic’s Dr. Daniel Lee.

Studies in the United States estimate that approximately 80 percent of men with HIV are circumcised, consistent with the general population of male circumcision rates.

The three African studies specifically studied those individuals who had circumcisions as adults, as opposed to having the procedure at birth.

For Lee, the recent buzz around the African studies is cause for some concern in the gay community.

“I agree that the studies provide valuable information, and they are interesting, especially for people in Africa,” Lee says. “But ultimately, in the U.S., HIV transmission comes down to risky behavior. Will people see this report and think, ‘Hey, I’m circumcised, so I won’t get HIV? Yes. Will there be those who think, falsely, they are protected? Yes. I think that, ultimately, [HIV transmission in the U.S.] is more about behavior of using condoms and other things that may offer better prevention in terms of HIV infection. Circumcision in no way reduces your potential risk to zero.”

As for whether the same results would be found in the U.S., or, at the very least, lead to a significant reduction in HIV, both Lee and Little are cautious.

“I’m not sure that this is necessarily a great strategy for here in the U.S. because there are so many differences between the populations of the African studies and those in the U.S.,” Lee argues. “Ultimately, people are going to have to make their own choice, which is something that in the U.S., with the level of access to education and health care that most Americans have – that alone makes me concerned.”

Little agrees.

“We need studies here in the U.S. to answer that question,” Little argues, “We have had some smaller studies in populations of MSM that do demonstrate the same trends, but they are not the kind of elegant studies done in Africa. They’re good studies, but what we lack are prospective, randomized studies, and that’s the gold standard of studies.”

While there have been some studies in the U.S. regarding circumcision and HIV transmission, they lack the statistical reliability of the African studies, which had thousands of participants, thus making the data more reliable. Both smaller studies in the U.S. – one published in May 2005 in the Journal of Acquired Immune Deficiency Syndrome, and the other more than a decade earlier in the 1993 Annual Internal Medicine Report – have shown that uncircumcised men were twice as likely to be at risk for HIV seroconversion. According to the CDC, in both studies “the results were statistically significant and controlled statistically for other possible risk factors.” A third study, though, of heterosexual men in an urban sexually transmitted disease (STD) clinic showed uncircumcised men had a 3.5 times higher risk of HIV infection than men who were circumcised. The sampling was, however, too small to qualify the association as statistically significant.

In other words, the U.S. needs a study to determine whether circumcision in MSM populations – those who make up a much higher percentage of HIV transmissions – does, in fact, lower the risk for the insertive partner for HIV.

UCSD’s Little currently is involved in a study at UCSD, funded by the National Institute of Health, on newly infected gay men and their partners. The study is attempting to address issues that both increase and decrease the risk of HIV transmission. Circumcision is one of the variables being studied.

“The study is looking to identify those things that are most highly associated with transmission or protection, such as increased viral loads, illicit substances, etc., and yes, circumcision is among those being studied,” Little said.

The study, being conducted at UCSD’s Antiviral Research Center (AVRC) is actively seeking participants. Prospective participants should contact the screening coordinator at AVRC by calling 619-543-8080 and asking for the coordinator of the early test program.