Show me the Evidence

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Clinical Trial Sparks Male Circumcision Programs to Prevent HIV Infection

UNAIDS and WHO moved quickly after results published

In early 2011, more than 10,000 boys and men in Tanzania were circumcised in just six weeks, the result of a highly organized public health campaign. The government there is planning 2.8 million circumcisions over five years.¹ Kenya has provided voluntary male circumcision to 330,000 since 2007.² In all, more than 600,000 circumcisions³ have been performed in the countries of southern and eastern Africa.

Usually it takes years – sometimes decades – for research results to be translated into clinical practice. This particular intervention, shown to be a highly effective way of preventing the transmission of HIV, appears to be an exception. How and why was this the case? The story involves a long-term commitment from Dr. Stephen Moses, early support from the Canadian Institutes of Health Research (CIHR), decisive action from the World Health Organization (WHO) and UNAIDS, and, along the way, a tribute from Time magazine, which rated the work as the number one medical breakthrough of the year in 2007.

A University of Manitoba medical researcher who has spent much of the last 25 years in Africa, Dr. Moses was involved in some of the earliest studies to observe that African populations with higher levels of male circumcision had significantly lower levels of HIV prevalence.⁴ "It was quite exciting because at the time there weren't a lot of options for HIV prevention other than condoms," he says.

In 2001, he co-authored a review of what had become a growing body of studies that suggested a direct link existed between male circumcision and lower HIV prevalence.⁵ The link is based on the belief that because the foreskin's inner mucosa is rich in HIV target cells, removing it greatly reduces the risk of transmission of the virus from women to men.⁶ However, Dr. Moses' review concluded that clinical evidence was needed before communities and international health organizations could be encouraged to promote the practice.

"It's a surgical procedure," says Dr. Moses. "It's permanent; there are complications that occur from time to time. The prevailing opinion became: unless there was evidence from clinical trials, it wasn't going to be advocated."

He worried that conducting a large-scale clinical trial might be impossible; however, research suggested it could work. "My colleague, Robert Bailey, from the University of Illinois at Chicago, with colleagues from Kenya, conducted a study where they asked young men in the Nyanza province of Kenya, where most men traditionally are not circumcised, if they would be willing to participate in such a trial, and the vast majority said that they would. That was a bit of a surprise."

Evidence in Action: Cost-Effective Infection Prevention

According to an expert panel convened by UNAIDS, the World Health Organization and the South African Centre for Epidemiological Modelling and Analysis, one new HIV infection would be averted for every 5 to 15 men circumcised in settings where HIV prevalence exceeds 15% of the general population. Given that adult male circumcisions cost between $30 and $60, the estimated cost "per infection averted" is between $150 and $900 over 10 years. In contrast, the cost of low-priced treatment per HIV infection typically exceeds $7,000 if first-line antiretroviral treatment only is provided. Should that treatment fail and follow-up therapy be required, the estimated cost exceeds $14,000 per infection over the same 10-year time span.⁷

Dr. Moses and his colleagues wrote a CIHR grant application to support a randomized controlled trial that was approved and funded in early 2001. Later that year, the National Institutes of Health in the United States approved another grant application for the project. By early 2002, they had begun recruiting 18- to 24-year-old men from Kenya's Luo ethnic group. In late 2006, when early results indicated the participants undergoing circumcision were at a far lower risk of contracting HIV, the research team decided it would be unethical to deny the control group the procedure. "We didn't stop the study," says Dr. Moses, "but we stopped the randomization and offered to everybody in the control group the opportunity to be circumcised."

WHO and UNAIDS Act Quickly on Findings

The results of the study, published in The Lancet in February 2007, showed a 60% reduction in the risk of acquiring an HIV infection among the circumcised men.⁸ A comparable randomized controlled trial in Rakai, Uganda found similarly striking results, and a study in Orange Farm, South Africa had also produced promising findings in 2005. Time magazine hailed the news as the top medical breakthrough of 2007.

Based on the evidence, WHO and UNAIDS quickly endorsed the procedure as "a significant step forward in HIV prevention"⁹ and identified 14 countries in southern and eastern Africa for scale-up of male circumcision programs.¹⁰

"The studies by Dr. Moses and his colleagues were really critical in convincing any skeptics that circumcision is an effective intervention," says Dr. Mores Loolpapit, an Associate Director at Family Health International (FHI 360), and manager of the Male Circumcision Consortium in Kenya. "The research work offered the basis for initiating scale-up of male circumcision for HIV prevention in eastern and southern Africa."

Evidence in Action: A New Weapon in the Fight Against HIV/AIDS

Since the international initiative began, Kenya alone has provided 330,000 medical male circumcisions since 2007, followed by South Africa at 141,000, Zambia at 81,000, Tanzania at 42,000, and Zimbabwe at 21,000, according to UNAIDS.

The impact has been significant. Along with major campaigns in Kenya, Swaziland, which has the highest HIV prevalence rate in the world at 26% of adults aged 15 to 49 years, has launched a plan to provide voluntary medical male circumcision to 152,800 men. Since the international initiative began, over 141,000 medical male circumcisions have been performed in South Africa, 81,000 in Zambia, 42,000 in Tanzania, and 21,000 in Zimbabwe, according to UNAIDS.¹¹

"Rapid scale-up will not only reduce the risk of HIV infection in men more quickly but women will benefit faster too as the chance of meeting a sexual partner who has HIV infection will be less," says Dr. Catherine Hankins, Chief Scientific Adviser to UNAIDS.

For Dr. Moses, who continues to work in Kenya but is now primarily involved in HIV prevention programs and research in India, the translation of the research work into policies and actions has been gratifying. "Definitely. There is a lot more to do but I think that male circumcision services are scaling up quickly, and programs are picking up steam. I'm pretty optimistic." 

CIHR Was First to Fund the Randomized Controlled Trial

"It was really important that CIHR got things going. Of the three trials that eventually were done in Africa – the other ones were in Uganda and South Africa – our Kenyan one was the first one to be supported, and CIHR was the first funder," says Dr. Moses.

1. UN welcomes data showing male circumcision can help prevent HIV in men, UN News Centre, July 21, 2011.
2. Email correspondence with Dr. Mores Loolpapit, manager of the Male Circumcision Consortium in Kenya.
3. Total number based on figures supplied by UNAIDS and the Male Circumcision Consortium of Kenya.
4. Geographical patterns of male circumcision practices in Africa: association with HIV seroprevalence. International Journal of Epidemiology 19, 3 (1990): 693–697.
5. Male circumcision and HIV prevention: current knowledge and future research directions, The Lancet Infectious Diseases 1 (November 2001): 223–231.
6. The Future Direction of Male Circumcision in HIV Prevention, Conference Proceedings, Nov. 29–30, 2007, Los Angeles, U.S. Published July 2008.
7. Male Circumcision for HIV Prevention in High HIV Prevalence Settings: What Can Mathematical Modelling Contribute to Informed Decision Making? PLoS Medicine 6, 9 (2009): e1000109. doi:10.1371/journal.pmed.1000109.
8. Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomised controlled trial. The Lancet 369 (Feb. 24, 2007): 643–656. Excerpt from paper: "The as-treated analysis – which adjusted for individuals who did not adhere to the randomisation assignment – estimated the RR [risk ratio] of circumcision to be 0.45 (95% CI 0.27–0.76). Excluding the four participants who were confirmed as being HIV positive at baseline, the RR of circumcision was 0.40 (0.23–0.68), which is equivalent to a 60% (32–77) protective effect of circumcision against HIV acquisition … For planning purposes, the 60% protective effect probably represents the more accurate estimate of the treatment effect, since it compares truly circumcised HIV-negative men to truly uncircumcised HIV-negative men post-randomisation."
9. WHO and UNAIDS announce recommendations from expert meeting on male circumcision for HIV prevention, Press Release, March 28, 2007.
10. Towards Universal Access, Scaling up priority HIV/AIDS interventions in the health sector, WHO, UNAIDS, UNICEF Progress Report 2010, 3.2.1 male circumcision. Note: Originally Botswana, Kenya, Lesotho, Malawi, Mozambique, Namibia, Rwanda, South Africa, Swaziland, United Republic of Tanzania, Uganda, Zambia and Zimbabwe were identified for scale-up. Ethiopia was added as a target country.
11. Global Report: UNAIDS Report on the Global AIDS Epidemic 2010.