Adult male circumcision reduces risk for HIV

Two clinical trials of adult male circumcision have been halted after an interim review of data showed medically performed circumcision significantly lowers a man's risk of acquiring HIV through heterosexual intercourse.

Interim data from one trial in Kisumu, Kenya, of 2,784 HIV-negative men showed a 53% reduction of HIV acquisition in circumcised men compared to uncircumcised men, while a trial of 4,996 HIV-negative men in Rakai, Uganda, reflected a 48% drop in HIV acquisition in circumcised men. Both trials were funded by the National Institute of Allergy and Infectious Diseases (NIAID); the Kenyan trial also was supported by the Canadian Institute of Health Research.

The results from the two trials support similar findings from the earlier South Africa Orange Farm Intervention Trial, conducted near Johannesburg, South Africa. The Orange Farm trial demonstrated at least a 60% reduction in HIV infection among circumcised men.1

"We now have confirmation — from large, carefully controlled, randomized clinical trials — showing definitively that medically performed circumcision can significantly lower the risk of adult males contracting HIV through heterosexual intercourse," says Anthony Fauci, MD, NIAID director. "While the initial benefit will be fewer HIV infections in men, ultimately adult male circumcision could lead to fewer infections in women in those areas of the world where HIV is spread primarily through heterosexual intercourse."

At press time, the American Academy of Pediatrics had not changed its neutral stance on the procedure.

Both of the NIAID-funded trials enrolled adult, HIV-negative heterosexual men, who were randomized to circumcision performed by trained medical professionals in a clinic setting or no circumcision. All men were counseled in HIV prevention and risk reduction techniques.

Both trials originally were designed to continue follow-up until mid-2007; however, at a regularly scheduled review in December 2006, panel member reviewers concluded that the interim data demonstrated that medically performed circumcision is safe and effective in reducing HIV acquisition. The reviewers recommended the two studies be halted early, and all men who were enrolled be offered circumcision.

Two common circumcision procedures were used in the two trials. Researchers in the Kenyan trial performed circumcision using the foreskin clamp method, and stitches to control bleeding and improve wound closure. Scientists in the Ugandan trial used the sleeve method of circumcision and relied on cauterization of the blood vessels to control bleeding and stitches to close the wound.

While the current trials' results demonstrate the impact of male circumcision on male acquisition of HIV, the method does not provide complete protection against HIV infection, say international public health officials.

Circumcised men still can become infected with the virus and, if HIV-positive, can infect their sexual partners, according to a statement issued by the World Health Organization, the United Nations Population Fund, the United Nations Children's Fund, the World Bank, and the UNAIDS Secretariat.2

"Male circumcision should never replace other known effective prevention methods and should always be considered as part of a comprehensive prevention package, which includes correct and consistent use of male or female condoms, reduction in the number of sexual partners, delaying the onset of sexual relations, and HIV testing and counseling," officials note.

How does male circumcision reduce a man's risk of HIV infection? Medical experts point to a number of potential mechanisms:

  • The foreskin's inner mucosal surface has more immune cells vulnerable to HIV infection than the external surface.
  • The foreskin acts as a physical barrier that can trap HIV next to the mucosal surface of the penis. In this moist environment, the virus also can survive longer, potentially increasing the risk of infection.
  • Small tears in the foreskin that may occur during intercourse can promote entry of the virus. The penile shaft and glans develop more epithelial keratinization following circumcision, making the penis less susceptible to viral invasion.3

While the findings from the African studies offer hope in fighting HIV on the international front, they may have less impact on the U.S. epidemic, say public health officials. Most men have been circumcised in the United States; also, most infections among men in the United States are in men who have sex with men, in which case the benefit of circumcision is not presently known. The Centers for Disease Control and Prevention is undertaking additional research and consultation to evaluate the potential value, risks, and feasibility of circumcision as an HIV prevention intervention in the United States.

Robert Hatcher, MD, MPH, professor of gynecology and obstetrics at Emory University School of Medicine in Atlanta, says, "My concern is that the important protective effect of male circumcision will be interpreted to mean, 'We don't need to use condoms.' Murphy's law tells us this is exactly what will happen, and all of us in reproductive health must be aware of this unfortunate response."

Does male circumcision extend its protective effect to women? Researchers at Johns Hopkins University in Baltimore currently have an ongoing trial to answer that question, says Ronald Gray, MBBS, MSc, the William G. Robertson professor of reproductive epidemiology at the university's Bloomberg School of Public Health; Gray led the investigative team responsible for the Uganda trial. The study involving women will not be finished until 2008, says Gray.

References

  1. Auvert B, Puren A, Taljaard D, et al. Impact of male circumcision on the female-to-male transmission of HIV. Presented at the International AIDS Society Conference on HIV Pathogenesis and Treatment. Rio de Janeiro; July 2005. Abstract TuOa0402.
  2. World Health Organization, United Nations Population Fund, United Nations Children's Fund, World Bank, UNAIDS Secretariat. Statement on Kenyan and Ugandan trial findings regarding male circumcision and HIV. Press release. Dec. 6, 2006. Accessed at: www.who.int.
  3. National Institute of Allergy and Infectious Diseases (NIAID). Questions and Answers. NIAID-Sponsored Adult Male Circumcision Trials in Kenya and Uganda. Media release. Dec. 13, 2006.