STD Quarterly

Male circumcision and HIV prevention: Method can dramatically reduce risk, study says

More research to assess method as risk prevention tool will be completed in ’07

No doubt you have scanned news reports of a recent study of male circumcision, used as an HIV prevention intervention, which resulted in dramatic reduction in HIV incidence among circumcised men.1 But does the news translate into an immediate change in public health policy?

The trial, which looked at men ages 18-24 in the Gauteng province in South Africa, is the first randomized control trial to demonstrate a strong protective effect of safe male circumcision on HIV acquisition by males, says Bertran Auvert, MD, PhD, professor of public health at the University Versailles Saint-Quentin in Paris.

Auvert and his research team presented the findings at the recent International AIDS Society conference in Rio de Janeiro, Brazil.

Researchers randomly assigned the men, all heterosexual males living in a high HIV prevalence area, to undergo circumcision or wait 20 months for the procedure. Previous acceptability studies had shown that men in the area would consider circumcision if it would reduce the risk of HIV. The randomized trial, which began in 2002, was halted early after initial results indicated that the intervention prevented six to seven out of 10 potential HIV infections.1

While the results of the study are being met with interest, more work will be needed to confirm its results, say officials with the Joint United Nations Programme on HIV/AIDS (UNAIDS).

"Although the trial shows promising protective effects of adult male circumcision in reducing HIV acquisition, UNAIDS emphasizes that more research is needed to confirm the reproducibility of the findings of this trial and whether or not the results have more general application," noted the organization in a statement issued after the conference presentation. "In particular, the findings from two ongoing trials in Uganda and Kenya, funded by the U.S. National Institutes of Health, will be important to clarify the relationship between male circumcision and HIV in differing social and cultural contexts."2

What role might circumcision play in the prevention of HIV acquisition? Scientists propose that the inner surface of the foreskin, which contains Langerhans cells, may provide a potential source of initial cell contact for HIV infection.3 The foreskin also may offer an environment for survival of bacterial and viral matter, since it is susceptible to tears, scratches, and abrasions.4

The idea that male circumcision may lower the risk of HIV acquisition is not new; such a hypothesis was raised early in the AIDS crisis.5 Scientists have noted the highest rates of HIV infection in Africa have occurred in regions of the continent where the predominant tribal or religious cultures do not practice circumcision. Adult HIV infection rates above 30% are found in Zimbabwe, Botswana, Swaziland, and eastern South Africa, where circumcision is not practiced, while HIV infection rates remain below 5% in West Africa and other parts of the continent where circumcision is commonplace.6

Scientists have continued to examine circumcision’s role in a number of observational studies. A meta-analysis published in 2000 of 27 such studies concludes that the practice is associated with a significantly reduced risk of HIV infection among men in sub-Saharan Africa, particularly those at high risk of HIV.7

International researchers projected new directions for further research at a February 2000 meeting organized by the Horizons Project of the New York City-based Population Council. They called for not only research on the mechanisms and expected effect of male circumcision on HIV infection and the possible existence of serious confounders, but they also called for studies on the practicality, feasibility, acceptability, and cost-effectiveness of male circumcision as an HIV intervention.8

Look for more results

Scientists are moving forward with two other randomized control trials, both designed to assess whether circumcision of adult males protects against HIV. One such study is under way in Kisumu, Kenya, led by Robert Bailey, PhD, MPH, professor of epidemiology and biostatistics at the University of Illinois at Chicago; the other, centered in Rakai, Uganda, is headed by Ronald Gray, MD, MSc, professor of reproductive epidemiology at Johns Hopkins University in Baltimore. The National Institute of Allergy and Infectious Diseases is providing funding for both trials.

The Kenya research, conducted in an area where less than 10% of adult men are circumcised, is being designed to assess the effectiveness of male circumcision in reducing HIV incidence. Uncircumcised men ages 18-24 years old will be offered voluntary HIV counseling and testing. HIV-negative men will be asked to enroll in the study. Consenting men will be assigned randomly to the treatment (circumcised) arm or the control (uncircumcised) arm of the study. Follow-up visits will be scheduled every six months for two years. Uncircumcised men will be offered circumcision at the end of follow-up. Enrollment of the 2,700 men is under way, and the trial is expected to be completed in 2007.

In the Uganda trial, enrollment of 5,000 HIV-negative men has been completed, Gray reports. The study’s review board will decide on when an interim analysis might be done. One was planned for mid-2006, Gray states. The final study will be completed in mid-2007.

What is the next step?

If research confirms that male circumcision is an effective intervention in reducing HIV risk, men should not assume that they will be protected from acquiring the virus through circumcision alone, UNAIDS officials state. If effective, the method should be presented as part of a comprehensive prevention package, which includes correct and consistent condom use, behavior change, and voluntary counseling and testing, according to UNAIDS.

Africa has the highest HIV/AIDS infection rates in the world, with more than 25 million people infected. News of the South African trial may increase demand for male circumcision services, note UNAIDS officials.

"Although UNAIDS believes that it is premature to recommend male circumcision services as part of HIV prevention programs, there is heightened interest from governments and the general public in male circumcision in a number of African countries," state UNAIDS officials. "Governments should take steps now to ensure that male circumcision is conducted by trained practitioners in safe and equipped settings in order to reduce the rate of postoperative complications."

References

  1. Auvert B, Puren A, Taljaard D, et al. Impact of male circumcision on the female-to-male transmission of HIV. Abstract TuOa0402. Presented at the International AIDS Society Conference on HIV Pathogenesis and Treatment. Rio de Janeiro; July 2005.
  2. Joint United Nations Programme on HIV/AIDS. UNAIDS statement on South African trial findings regarding male circumcision and HIV. July 26, 2005. Accessed at: www.who.int.
  3. Soto-Ramirez LE, Renjifo B, McLane MF, et al. HIV-1 Langerhans’ cell tropism associated with heterosexual transmission of HIV. Science 1996; 271:1,291-1,293.
  4. Cameron DW, Simonsen JN, D’Costa LJ, et al. Female to male transmission of human immunodeficiency virus Type 1: Risk factors for seroconversion in men. Lancet 1989; 2:403-407.
  5. Fink AJ. A possible explanation for heterosexual male infection with AIDS. N Engl J Med 1986; 315:1,167.
  6. Russell S. Circumcision may offer Africa AIDS hope. San Francisco Chronicle, July 6, 2005: A2.
  7. Weiss HA, Quigley MA, Hayes RJ. Male circumcision and risk of HIV infection in sub-Saharan Africa: A systematic review and meta-analysis. AIDS 2000; 14:2,361-2,370.
  8. Van Dam J, Anastasi M. Male Circumcision and HIV Prevention: Directions For Future Research. Washington, DC: Horizons Project, Population Council; 2000.