March 2007

The National Institutes of Health announced late last year that it was halting two clinical trials in eastern Africa because an interim review revealed that safe male circumcision significantly reduced acquisition of HIV through heterosexual intercourse.
The trial in Kisumu, Kenya, showed a 53 percent reduction of HIV in circumcised men participating relative to uncircumcised men, while a trial in Rakai, Uganda, showed a reduction of 48 percent in circumcised men.

The news follows on the heels of a famous 2005 trial in South Africa that was also stopped early in the face of evidence that men who were circumcised were showing 60 percent fewer infections.

The findings have brought much buzz to the world of health care, which has spent many years looking for the “silver bullet” to end the global HIV/AIDS epidemic. But doctors are careful to warn that circumcision does not replace the need for men to wear condoms or limit risky behavior.

BOTUSA’s Associate Director for Science Dr. Doug Fleming has answered a few questions about the trials and their implications in places like Botswana.

What’s the real message from the preliminary results of these trials? Are we really telling men that if they are circumcised, their chances of getting infected by HIV are reduced by at least 50 percent?

Fleming: Yes. The results of the three trials were very clear and consistent. But we need to emphasize that the reduction in risk from circumcision depends on men maintaining safe sexual behaviors. HIV prevention from circumcision and from other means such a safer sex (using condoms, faithfulness, etc.) need to go together.

Can you explain how circumcision works? How does it help reduce chances of contracting HIV?

Fleming: The foreskin is very vulnerable to HIV infection. The inside of the foreskin is moist and delicate, and can experience small cuts where HIV can enter in to the body. The skin of the foreskin is also rich in cells that HIV can infect. So we would expect that removing the foreskin would reduce how vulnerable a man is to HIV, and how often he might transmit HIV to a partner. Further, once the foreskin is removed the tip of the penis dries and it becomes more difficult for HIV to enter in.

During circumcision, the foreskin is removed. In a doctor's office or health facility, the foreskin is carefully removed through a variety of specific methods, all of them with analgesia (to reduce pain) and with sterile conditions (to avoid infection). It is very important to avoid pain and infection.

Circumcision is not a new practice. So why are we only now learning about this tremendous benefit as a prevention tool?

Fleming: It has been suspected for a long time that circumcision protects against HIV. One of the earliest signs was that groups of people with high prevalence of male circumcision (like the Gikuyu in Kenya) had much lower prevalence of HIV infection. But no one could be sure if there might be other factors that could explain the low prevalence of HIV among circumcised men. Only a randomized controlled trial can answer this kind of question.

The decision to use male circumcision as a way to prevent HIV is a big one, since circumcision has potentially large benefits, but also has potential side effects. Only a randomized controlled trial can tell us with enough certainty what the balance is between benefits and risk.

Why were these trials stopped early?

Fleming: Running a trial is of great benefit for the nation when the trial can answer a question that we all need to know. Once that question is answered with certainty, then continuing the trial is of little further benefit. In fact, once the trial organizers in these recent trials knew that male circumcision worked, it was clear that circumcision should be offered to those men in the "control" group, that is, those men who had not been circumcised. This way, the men in the "control group" could receive the same benefit. Making sure that these men could receive circumcision was written into the procedures of the trial from the very beginning.

Do we need to conduct a similar trial in Botswana to determine if circumcision would have the same results here?

Fleming: No. In fact, it would likely be considered wrong and unethical to study people who have not received a procedure that we already know would help them.

Knowing these results, do you think the international community has a moral obligation to support the up-scaling of circumcision in African countries where HIV infection rate is high?

Fleming: Each country decides what is best for the health of the nation. It is wonderful to know that male circumcision is such a powerful resource for prevention, but the benefits and risks must be weighed carefully. Many other means of prevention are available and are important.

I am sure that many countries around the world will be examining the evidence for prevention with male circumcision, evaluating the side effects that were observed in the trials, and defining where male circumcision will fit in the nation's overall prevention program. Furthermore, they will need to look at the feasibility for each country. What are the operational implications, such as costs, who will do it and what policy changes will need to take affect?

Fleming: Personally, I do hope that those countries that choose to make male circumcision a part of their prevention program will receive support from the international community.

Would the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) support efforts to upscale circumcision?

Fleming: Shortly after the trial results were announced, Ambassador Mark Dybul issued a statement, part of which says:

"PEPFAR is awaiting normative guidance from international organizations or other normative bodies, and thereafter will support implementation of safe medical male circumcision for HIV/AIDS prevention based on requests from host governments and in keeping with their national policies and guidelines. It is important that male circumcision be safely provided and that it be integrated into, and not substituted for, a comprehensive HIV/AIDS prevention program."

No country has adopted a public health policy on circumcision, though several African countries are in consultations over how to do so. What are the risks in making circumcision part of a government’s policy?

Fleming: The risks of circumcision itself are the immediate side effects (pain and infection). Fortunately, these seem to be relatively low risks if the procedure is done carefully in a health facility, with proper equipment and well trained personnel.

Perhaps the biggest risk is that circumcised men might consider themselves to be fully protected from HIV. They might then engage in riskier activities, which might partly cancel the benefit of male circumcision. It is for this reason that Ambassador Dybul emphasized that "prevention efforts must reinforce the ABC approach – abstain, be faithful and correct and consistent use of condoms, and must be linked to voluntary counseling and testing and screening and treatment of sexually transmitted infections."