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Posted: 3 Nov 2011
30 years in 30 weeks, 2007

It is not often that a scientific discovery makes a rapid and direct impact on public health, but this is exactly what happened when three trials testing the impact of male circumcision on HIV acquisition showed efficacy. Guidelines were released and quickly adopted by many countries in Africa, which started providing circumcision to men. The road to success, however, was not as straightforward as it may appear with initial observations of protective effects of circumcision being made more than a decade earlier. In his commentary Dr. Moses provides the history of circumcision as a means of protecting men from HIV infection.

Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomised controlled trial.
Lancet. 2007 Feb 24;369(9562):643-56.
Bailey RC, Moses S, Parker CB, Agot K, Maclean I, Krieger JN, Williams CF, Campbell RT, Ndinya-Achola JO.

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Commentary by Dr. Stephen Moses

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Dr. Stephen Moses
In 1989, a paper in the Lancet reported on a clinical study conducted at the central STD clinic in Nairobi, Kenya. This collaborative study, involving researchers from the Universities of Nairobi and Manitoba, described a remarkable and largely unexpected finding:  uncircumcised HIV seronegative men with a genital ulcer had an HIV seroconversion rate of over 50% over the ensuing 9 months of follow-up compared to 2.5% in circumcised men without a genital ulcer.  Over the first two decades of the HIV epidemic, the association between circumcision and HIV infection was confirmed in numerous observational epidemiological studies.  However, by the end of the 1990s, it became clear that randomized controlled trials (RCTs) would be necessary before male circumcision could be promoted as an HIV prevention measure. In the absence of positive results from RCTs, it was not possible to rule out the many factors which may have confounded the observed relationship between male circumcision and HIV infection, the most important being sexual behaviour.

Because male circumcision, or lack thereof, was thought to be an ingrained cultural practice in African societies, circumcision acceptability studies were undertaken in a number of African countries and the response from most communities was generally very positive.  In Kenya, the main concentration of uncircumcised men resides in Nyanza Province, in western Kenya.  To our surprise, men there indicated not only that they would accept circumcision, but that they would be willing to participate in a randomized trial; that is, they would agree to be circumcised if randomized to the treatment group and to remain uncircumcised for at least two years if randomized to the control group. After enlisting the support of community, political, religious and cultural leaders, funding for the trial in Kenya was obtained in April 2001 from the Canadian Institutes of Health Research (CIHR), and subsequently, from the US National Institutes of Health (NIH).  The Kenyan trial was a collaborative effort among the Universities of Nairobi, Manitoba, and Illinois at Chicago.  Two similarly designed trials, one in South Africa and one in Uganda, commenced shortly thereafter.

All three trials were stopped before their planned endpoints, because the efficacy of circumcision was clearly demonstrable by the time of stoppage.  The results of the South African trial were published in October 2005, and the Kenyan and Ugandan trials in February 2007.  The protective effects in the three trials were remarkably similar, and very close to the effect seen in earlier observational studies: the pooled protective effect from the three trials was about 56%.  Although follow-up in the main trials was only for 21-24 months, long-term follow-up of the cohorts in Kenya and Uganda (albeit no longer blinded), has shown that the protective effect persists for at least five years post-circumcision, and there is a suggestion that it may increase over time.  In addition, there were relatively few serious complications of the surgical procedure, and none that did not satisfactorily resolve.  Another major concern, risk compensation, or behavioural disinhibition, did not seem to occur in the trials.  However, as male circumcision services expand, it will be important to carefully monitor safety and risk compensation, as experiences with the general population of men who access regular health services may be very different from those observed in a clinical trial.

It has been estimated, from mathematical modelling, that male circumcision in sub-Saharan Africa could avert over 7.7 million HIV infections and 3 million AIDS deaths over the next 20 years, and that it is cost-effective, with a cost of about $181 per HIV infection averted in the context of a high HIV prevalence country like South Africa.

Following the publication of the three trials, international authorities moved quickly, and male circumcision was endorsed as an effective HIV prevention measure by UNAIDS and WHO.  All 13 of the countries in eastern and southern Africa with high prevalence of heterosexually transmitted HIV infection and large populations that do not practise male circumcision, have developed plans to scale up male circumcision services to assist in their HIV prevention efforts.  Country policies and task forces have been put into place, often with allocation of significant local resources. The initiative to expand male circumcision services has also received considerable external support from the Bill & Melinda Gates Foundation, and the United States government’s President’s Emergency Plan for AIDS Relief (PEPFAR).  Early reports suggest that the demand for male circumcision services in many of these countries is rising rapidly. Approximately half a million medical male circumcisions have been performed over the past two years in countries in eastern and southern Africa, among men who would not normally have been circumcised.  However, there is still a long way to go to reach the target of 12 million uncircumcised men in those countries. The challenge for health systems is to expand and strengthen in order to ensure the availability and accessibility of high-quality services to meet the demand. It is critical that such services be safe, and include adequate counselling to reduce the likelihood of risk compensation.

The three clinical trials were complex undertakings, requiring expertise in a variety of different disciplines, including epidemiology, medicine, microbiology and social sciences.  The success of the trials is a tribute to the strength of the collaborative groups which were assembled in each country, and the support of the funders.  Most importantly, it is a tribute to the resolve and dedication of the African communities that participated in these trials and thereby contributed to their health and well being, and to the generation of important and relevant new knowledge.  The circumcision story shows how clinical research can be rapidly translated into public health action, and can ultimately improve the health of both individuals and populations.

About the author: Dr. Stephen Moses is a Professor at the University of Manitoba, Canada

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