Cutting HIV Transmission

Male circumcision as a potential HIV prevention strategy

By Sheri Fink, MD, PhD*

While the ultimate hope for stopping the AIDS epidemic, a vaccine, remains years away there may already be a way to effectively cut the sexual transmission of HIV—male circumcision. Scientists in eastern and southern Africa have been studying whether the surgical procedure can protect against HIV infection, and also what it would mean to promote for medical reasons a practice that has long held cultural significance.

Results from the first of three major randomized, controlled trials of circumcision were announced at the 3rd International AIDS Society Conference on HIV Pathogenesis and Treatment in Rio de Janeiro in July (see Brazil's model approach). The French National Agency for Research on AIDS and Viral Hepatitis (ANRS) sponsored the study involving over 3000 volunteers in Orange Farm, an urban area within South Africa’s Gauteng Province. The men were randomized to either receive circumcision immediately or defer the procedure for 21 months. Circumcision proved markedly protective. At the interim study evaluation three times fewer circumcised participants (18) had acquired HIV compared with control participants (51). The study’s Data Safety and Monitoring Board halted the trial and offered circumcision to members of the control group.

The results did not surprise many HIV prevention researchers since an inverse relationship between circumcision rates and HIV prevalence had been noted for years. An analysis of more than 30 observational studies—cross-sectional, case-control and cohort—suggested that circumcision might reduce the risk of HIV infection by 42%. The suggestion made sense, biologically. “The foreskin has HIV target cells which make it easy for HIV transmission and acquisition,” says Godfrey Kigozi, a co-principal investigator with the Rakai Health Sciences Program in southwestern Uganda, a body established in 1988 as the Rakai Project. “During sexual intercourse the foreskin is retracted, exposing a large surface area which is vulnerable to entry of HIV. Also, the foreskin is associated with genital ulcer disease (GUD), which makes entry of HIV into the body easy.”

Some researchers have likened circumcision for boys and men to a partially protective AIDS vaccine. “It is a procedure that a man undergoes once in their life; it would then provide some level of protection for the rest of their life,” says Maria Wawer of Johns Hopkins University in the US. “If circumcision is protective, its role in the fight against HIV could be really very dramatic.” An ongoing trial is investigating whether male circumcision can help prevent transmission of HIV from men to women. But even if there is no direct protective effect for women, if male circumcision can effectively lower transmission from women to men in a given population then eventually everyone will benefit—fewer transmitters mean that, overall, incidence rates will decline.

Kigozi and Wawer are two of the investigators leading an even larger randomized, controlled trial of male circumcision in progress in Rakai Province, Uganda, under the auspices of the Rakai Health Sciences Program. The US National Institutes of Health (NIH) sponsored the circumcision study because despite the considerable body of correlative research, the precise link between HIV infection and circumcision remained unclear. Public health experts have held back from recommending circumcision as an HIV preventive method because the observational studies had not established whether circumcised men were protected by circumcision itself or by other factors. For example, in many parts of Africa circumcised men are much more likely to be Muslim, and previous research conducted by the Rakai Program showed that Muslim men in the province tended to have fewer extra-marital partners than non-Muslim men. That raised the possibility that it was not circumcision that protected them but different sexual practices. “The only way you can really find out if circumcision protects men is to take a group of men who volunteer for a study and then randomly assign them to either get the circumcision right away or to delay the procedure” says Wawer.

Putting circumcision to the test

Rakai is a province of rolling hills, red dirt roads, and simple mud and brick dwellings. It is a community on the socio-economic rise, but many inhabitants still live off subsistence farming and do not enjoy electricity or motorized transport. They share the land with cows, corn, banana trees, and a profusion of birds. They also live close to the crossroads with Tanzania. The region was the site of considerable troop movements and unrest during Uganda’s civil war. In the 1980s Ugandan researchers including David Serwadda and Nelson Sewankambo of Uganda’s Makerere University were drawn here by reports of the mysterious illness they called “Slim Disease.” It later became known as AIDS. The researchers began studying the population and were joined by Wawer, Ron Gray, Tom Lutalo, and Fred Wabwire Mangen and others from the Ugandan Virus Research Institute (UVRI), Johns Hopkins University, and Columbia University.

Over the years the team has conducted many studies on HIV. The circumcision study is one of their latest. On a typical morning in the spring of 2005, around 40 potential study volunteers hiked or pedaled their bikes to the Rakai village of Kyawanyana. There they gathered under a blue and white striped tent and watched a video explaining the research. HIV prevalence is high in Rakai—one in eight adults—and the men were looking for ways to protect themselves. “I came here to learn how to avoid STDs,” says one.

After the video, the men were called one by one into small pup tents for individual counseling, physical exams and testing for HIV and other sexually transmitted diseases (STDs). They were urged to use condoms and practice safe sex. A day or two later, those who met the study criteria were invited to randomly select an envelope which informed them whether they would receive circumcision immediately or have to wait until the end of the two-year study period.

John Paul Wasa, a counselor, says that most men hope to receive immediate circumcision. “It might be STD/HIV prevention, it might be sexual prowess, it might be any other thing, but through the counseling process they get to know why we’d want them to remain in the arm in which they are randomized and the importance of that.” Rakai investigators know of only three cases where volunteers in the control group went elsewhere to obtain circumcisions prior to the end of the study.

The Rakai Program performs the circumcisions in a series of new, technically-advanced operating rooms in the small town of Kalicizo. Patients undergo circumcisions under local anesthesia. As of the spring of 2005 nearly 3,000 men had been circumcised, and a roughly equal number had been randomized to serve as controls. Only about 400 more surgeries remained.

Once they are enrolled, circumcised and uncircumcised men are followed closely for two years and regularly tested for HIV infection. “We are also looking at women to see whether circumcision in the male partner might reduce transmission of HIV and STDs to the woman partner” says Wawer. This latter research is part of a separate, concurrent study funded by the Bill and Melinda Gates Foundation. Rakai is the only one of the three sites to include analysis of male circumcision’s effect on HIV transmission to women.

This is just one of the reasons the Rakai Program investigators believe it is essential for their study to continue, even in light of the South African group’s finding that circumcision had a powerful protective effect against female-to-male HIV transmission. “There’s always a need to have more than one trial before you implement findings into policy,” says Kigozi.

Officials with the Joint United Nations Programme on HIV/AIDS (UNAIDS) agree. “The two other randomized controlled trials, currently ongoing in Uganda and Kenya with a combined total of nearly 8,000 participants, remain important to clarify the relationships between male circumcision and HIV,” said an agency statement. “The potential for negative or uncertain results in the other two trials cannot be ruled out at this stage.”

Challenges and suspicions

Now that at least one of the randomized controlled studies has shown that circumcision might help prevent HIV infection, public health experts are considering whether the practice should be promoted widely, and how. In Uganda some experts fear that if the demand for circumcision grows, villagers seeking to avoid the typical charge of roughly 50,000 Ugandan shillings—US$30—might turn to unqualified practitioners. If they re-use instruments between patients without proper sterilization they risk HIV infection. Every year, poorly-performed circumcisions lead to infections and disfigurement. Chief Rakai Program surgeon Dr. Stephen Watya, a consultant urologist at Makerere University’s Mulago Hospital, has treated the complications of some village circumcisers. “Recently I saw one young boy about five years with a severed glans, that’s the head of the penis being chopped off with the circumcision knife,” he says. “Occasionally that happens.”

The contrast between the Rakai Program’s state of the art operating theaters and the clinics where many African men receive circumcisions is remarkable. Just a few miles away traditional Muslim circumcisers perform their operations at a spartan clinic, the Kyotera Muslim Health Unit. A single bulb dangles from the ceiling of the circumcision room, which is nearly barren except for a bed. Each circumciser brings his own tools. “This room is small and there are no special facilities here. If you compare it with the [Kalicizo] theater, this is far below required standards,” says Sheik Badru Matovu who heads this clinic. Still, long-time circumciser Sheik Abudusamir Abudalazake Kakooza says that with education, many traditional and religious circumcisers in Uganda have modified their practices in order to decrease the risk of complications and contaminated equipment. Kakooza says his rate of complications is low. But no matter how advanced the facility, circumcision is never performed without risk: Rakai researchers report a 0.7% rate of serious complications, and about 1 in 20 patients overall experiences at least minor complications.

Even if circumcision is made relatively safe and affordable, how willing will men be to undergo the procedure? After all, circumcision is more than just surgery. It is a cultural and religious practice, it is wrapped up in tribal and personal identity, and many myths about it remain.

Back in the Ugandan village of Kyawanyana last spring, a group of men gathered for their post-operative check-ups. They say they’ve endured the disapproval of their fellow villagers. “Most people in our villages, our village men, tell us that you just want to stop us from having more children, as a form of family planning,” says one. Another agrees. His friends told him “these people just bring out the program so that they can castrate you.” A third shares a similar story. “People tell us in the villages there that we're just wasting our time. That AIDS, all the same, whether we get circumcised or not, AIDS is going to kill us. So all in all they tell us ‘you're just wasting your time, you'll just be like us, you'll still be wiped out!’”

Father Joseph Kato, a Catholic priest with the Matale parish in Rakai Province has been privy to another concern among his parishioners: that circumcision might turn them into Muslims. “ They came with that kind of fear. And I told them this has a medicinal purpose, preventing against HIV, rather than being something conversional. ” Other men express worries that their penis size will be reduced, or that they won’t be able to resume intercourse. In the US some anti-male-circumcision activists argue that circumcision reduces sexual sensation in men and that this could lead to even lower rates of condom use.

Still, the Rakai researchers say that men have been remarkably willing to undergo circumcision, even before knowing whether it was protective. “One of our secondary endpoints was to find out whether circumcision could be acceptable in these communities,” says Kigozi. “I think we have shown that circumcision can be acceptable, given the compliance we are seeing, given the overwhelming numbers that are coming to us to participate in this.” The South African team also studied the acceptability of circumcision and found that 70% of uncircumcised men expressed a willingness to undergo the procedure if it would reduce the risk of contracting HIV infection. Other acceptability research has yielded similar results, including a large Harvard AIDS Institute study in Botswana in which over 80% of uncircumcised men said they would undergo circumcision if it was performed safely and affordably.

False sense of security?

The scientists have another concern, though. Might circumcision change the men's sexual behavior? Perhaps they would feel immune from HIV and engage in more risky, unprotected sex, increasing their likelihood of acquiring—and passing—HIV infection. These questions are identical to those that would be raised by the development of a partially protective AIDS vaccine.

Jennifer Wagman heads up behavioral research at the Rakai Program. She is looking at how men perceive circumcision and whether circumcised men engage in practices that might put them at risk for HIV. One of those potential practices is known as “sexual cleansing.” “After they’re circumcised they have to go out and have sex with as many women as they can who are not necessarily their wives or main sexual partners,” says Wagman. “We don’t know if it’s happening, so we want to find out.”

Public health experts will have to take practices like this into consideration in any widespread effort to introduce circumcision. After the South African results were released, UNAIDS released a statement calling it “premature to recommend male circumcision services as part of HIV prevention programmes.”

Karusa Kiragu is a behavior change scientist with the Population Council in Nairobi, Kenya. “As a public health measure, it would have to be very carefully introduced into the communities with very, very strong education and would require a very significant paradigm shift,” she says. “The paradigm of the past was that upon circumcision in many communities, the boys then go on to become sexually active. From a public health point of view the paradigm would be that yes, you’re circumcised but no, it doesn’t mean that you now have permission to go and have sex. So, disentangling that for communities may be difficult.”

Difficult, yes, but possible, says Rakai Program principal investigator Fred Nalugoda. If circumcision is confirmed to be effective, he says, governments and other agencies should make an effort to provide the surgery to as many men as possible. “It would be unethical, once you learn something’s protective, to then withhold it from the people. I think what has to be combined with the provision is the intensive health education and counseling—telling people exactly what they have to do to counter their perception that maybe because it’s protective then they can do whatever they want with themselves.”

So far, the men in the Rakai Program study are not reporting higher risk behavior. The potential that circumcision might provide a whole new approach to stemming the tide of HIV has many scientists feeling hopeful, including Wawer. “We have all been looking for additional tools to use against this epidemic for the last 20 years. And it has been very disappointing how difficult it has been to come up with new tools.” An estimated 5 million people worldwide contracted HIV last year alone, and even a partial reduction in HIV risk could save thousands, perhaps millions, of lives.

*Sheri Fink, MD, PhD, is a freelance writer whose work has appeared in such publications as the New York Timesand Discover Magazine, and the author of War Hospital: A True Story of Surgery and Survival.