Sexual transmission of HIV

The biannual international microbicides conference “Microbicides 2008” will run 24 – 27 February in New Delhi under the theme “Striving towards HIV Prevention”.

The gathering will enable knowledge-sharing between microbicide researchers, public health workers and advocacy organizations and will provide a forum for the discussion of new developments in microbicide research including basic science, clinical trials and social science issues as well as discussion on behaviour, community engagement and advocacy.

In the second of a two part series looking at microbicides, we will be exploring some of these topics.

For several years, UNAIDS has insisted that the development of an effective microbicide is a public health priority and has emphasized the importance of access and affordability. However due to a lack of significant investment, the research and development pipeline has been slow and inefficient.

UNAIDS Executive Director, Dr Peter Piot said, “ The international community, including the private sector, must continue to invest in effective HIV prevention technologies that can be used by women .”

“Ensuring access to safe and effective microbicides will be of critical importance to all our prevention efforts and to our goal of stopping and reversing the epidemic.”

The cost of saving lives

The total global funding for microbicide research and development in 2006 done by the non-commercial sectors was $217 million. The pharmaceutical sector chooses to invest into the search for new antiretroviral drugs, attracted by a potentially large return-on-investment.

If there was comparable investment into microbicide research, it is thought that a safe and effective product would be on the market much sooner than a vaccine. However, as any microbicide would have to be affordable to consumers to whom it would make most difference – women living in low- and middle-income countries – the profit margins would be low. This economic reality makes microbicide research a less attractive investment.

As a consequence virtually all microbicide research is conducted by small biotech companies funded by the public sector.

Research and development pipeline

Research and development is continuing in spite of the large funding gap. More investment will be needed to bring clinical trials to completion and lay groundwork for distribution of an effective product.

As with any new drug, candidate microbicides must pass a series of rigorous laboratory tests and then a series of human clinical trials.

A range of contraceptive and non-contraceptive microbicide products are currently in different phases of development and trial including over 30 candidates in clinical trials. More than 30 others are in pre-clinical testing. However, results to date have been disappointing.

The microbicide search had an unexpected setback in February 2007 when an advanced Phase III study of a candidate microbicide Cellulose Sulfate was stopped early because women who used the gel were suspected to have a higher risk of HIV infection compared with women in the placebo group.

Earlier this week it was announced that Carraguard, a candidate microbicide that had completed large-scale Phase III trials, was unable to prevent HIV transmission. Encouragingly the product was found to be safe for long-term vaginal use making it the first microbicide Phase III trial to be completed without safety concerns. Researchers are hopeful this is a finding which will be built on.

“The next generation of antiretroviral-based microbicide products holds much promise. We do need to develop better safety biomarkers and improve measurements of adherence and we can learn much more from trials which have not resulted in an effective product,” said UNAIDS Chief Scientific Adviser, Dr Catherine Hankins.

Timing of microbicide availability

The Global Campaign for Microbicides estimated that if one of the products in advanced clinical trials proves to be effective, a microbicide could be ready for distribution in a small number of countries by the end of 2010. However, if the current sets of products do not prove effective, the timeline will be longer.

Next steps

Next week’s Microbicide conference will be an important forum for the discussion of the challenging issues of research, financing, clinical trials and ethical considerations.

Experts will gather to hear updates on current and emerging candidate product trials and will debate a range of topics. UNAIDS Chief Scientific Adviser Dr Catherine Hankins will make presentations on the implications of the results of male circumcision trials for microbicide research and present findings from the December 2007 consultation “Making HIV trials work for women and adolescent girls”.

UNAIDS Executive Director Dr Peter Piot will address the conference closing ceremony which will be attended by politicians, policy-makers, scientists, community activists and other AIDS experts.

The London School of Hygiene and Tropical Medicine estimated by mathematical modelling that the introduction of even a 60% effective microbicide into the world’s 73 lowest-income countries which would be used by only 20% of women already in contact with health services could avert up to 2.5 million infections in three years.

With many observers confident that a successful microbicide could make a significant impact in HIV prevention around the globe, the wait is all the more frustrating, the set-backs all the more disappointing.

Ahead of next week’s biannual international microbicides conference Microbicides 2008 running 24 – 27 February in New Delhi we take an in-depth look at microbicides. In part 1 of this 2-part series we look at why they are considered significant in the response to HIV. In part 2 the challenges to the development of this biomedical prevention technology will be explored.

While the search for a HIV vaccine looks
set to continue for some years, many
believe that with similar investment a s
uccessful microbicide could be developed
much sooner.

With 2.5 million people newly infected with HIV in 2007 there is global consensus on the need for new HIV prevention technologies to complement existing strategies.

While the search for a HIV vaccine looks set to continue for some years, many believe that with similar investment a successful microbicide could be developed much sooner. An effective microbicide would offer significant protection to women who currently comprise about half of all people living with HIV worldwide.

UNAIDS works with number of microbicide networks to highlight the critical need for female-controlled prevention options.

Along with other global advocates, UNAIDS continues to emphasize the importance of a concerted effort to develop microbicides and make them accessible to the people that need them. Addressing women’s needs for HIV prevention is vital for curbing the epidemic.

Why do women need specific HIV protection?

It is an uncomfortable reality that many women across the globe do not have power over what happens to their own bodies.

Deep-seated social and cultural norms and the effects of gender inequality mean many women and girls live with violence or the threat of violence and are unable to successfully negotiate fidelity or condom use.

Women who sell sexual services are often unable to negotiate the wearing of condoms with their clients.

Even women abstained from intercourse before marriage and have only one sexual partner can be vulnerable to sexually transmitted infections from partners if that partner engages in unprotected sex with other women or men.

“Microbicides will be a key tool in
empowering women, and in halting the
alarming spread of HIV infection among
women” - Director of the Global Coalition
on Women and AIDS, Kristan Schoultz.
Credit: UNAIDS/C.Gira

Due to biological differences, in unprotected heterosexual intercourse women are at least twice as likely as men to acquire HIV from an infected partner. HIV data reflects this, for example among young people (15-24 years) in sub-Saharan Africa an estimated three young women are HIV-positive for every young man.

Experts believe if women have the option of using a microbicide to protect themselves from HIV it could make all the difference to their lives.

“A man may refuse to wear a condom and his partner may be powerless to insist. Access to safe and effective microbicides will offer women more choices and help them take charge of their sexual health and their future,” said Director of the Global Coalition on Women and AIDS, Kristan Schoultz.

“Microbicides will be a key tool in empowering women, and in halting the alarming spread of HIV infection among women,” she added.

What is a microbicide?

A microbicide is a compound whose purpose is to reduce the infectivity of viruses or bacteria. The term has come to refer to a potential product which would prevent the transmission of HIV and other sexually transmitted infections (STIs) inside a woman’s vagina. A rectal microbicide would act similarly to protect men who have sex with men and women during anal intercourse.

There are different candidate microbicide products currently under research and development; many are in the form of a gel or cream to be applied to the surface of the vagina. Scientists are also exploring other ways of drug delivery such as by a vaginal ring which would be inserted into the vagina and provide controlled release of an effective microbicide.

Mechanisms of action

A successful topical microbicide – applied to the vagina surface - would probably act in a combination of ways. Scientists are researching different products which would:

1. Kill pathogens without damaging the healthy cells of the vagina
2. Strengthen the body’s natural defence system by increasing the natural acidity of vagina inactivating athogenic viruses and bacteria
3. Inhibit the virus getting into the white blood cells – the target cells of HIV
4. Inhibit viral replication by using derivatives from anti-retroviral drugs

For some women, it is important that the action of the microbicide not impair their ability to conceive a baby. Both contraceptive and non-contraceptive microbicides are currently under development, as well as rectal microbicides for heterosexual women and men who have sex with men.

No silver bullet

The biannual international microbicides
conference “Microbicides 2008” will run
24 – 27 February in New Delhi under the
theme “Striving towards HIV Prevention”.
Credit: Microbicides 2008

Some advocates believe that the successful development of a microbicide would bring significant emancipation for women who due to cultural, economic and social drivers are disempowered and unable to protect themselves from HIV.

With the stakes so high, microbicides seem like a very attractive solution. However experts are realistic about the complexity of the research task and drug efficacy and urge caution over raising unrealistic expectations.

Successful microbicides products will be partially protective. Although they may be up to 80% effective in preventing the transmission of HIV during sexual intercourse, they would need to be complimented by other prevention tools in a combination prevention strategy.

A comprehensive HIV prevention package includes, but is not limited to, delaying sexual debut, mutual fidelity, reduction of the number of sexual partners, avoidance of penetration, safer sex including correct and consistent male and female condom use, and early and effective treatment for sexually transmitted infections.

In part 2 we look at the challenges in current microbicide research and development and explore why there is a large funding gap between what is needed to bring clinical trials to completion and lay groundwork for effective distribution and what is currently available. We also look at the ethical considerations of clinical trials.

15th Conference on Retroviruses
and Opportunistic Infections took place in
Boston 4-6 February 2008. Credit: CROI

The annual Conference on Retroviruses and Opportunistic Infections (CROI) began in 1994 as a small meeting of scientists studying HIV and clinicians treating people with HIV. It is now one of the most important annual HIV gatherings and provides a forum for basic scientists, clinical investigators, and global health researchers to present, discuss, and critique their investigations into the epidemiology and biology of human retroviruses and the diseases they produce.

The 15th CROI concluded in Boston on 6 February and while announced trial results were not encouraging, many significant topics were discussed. The absence of a scientific breakthrough in HIV vaccine development underscores the need to scale-up existing prevention and treatment strategies.

HSV-2 trial - No observed reduction in risk

Disappointing results were announced from trials to see if ongoing treatment of the virus that causes herpes in humans, herpes simplex virus type 2 (HSV-2), would reduce the risk of HIV transmission. HIV-negative people with HSV-2 were asked to take medication to suppress outbreaks of herpes. However, the trial results showed no difference in rates of HIV infection between individuals who had taken the medication and those who hadn’t.

Scientific data shows a link between HSV-2 infection and susceptibility to acquiring HIV infection and there are other on-going trials exploring different aspects of this link, so researchers remain cautiously hopeful about this avenue of research.

Male circumcision

Previously-released data from the studies of male circumcision in Uganda which were stopped in December 2006 were presented by trial investigator Maria Wawer. One trial explored whether circumcising a HIV-positive man reduced the risk of HIV transmission to his HIV-negative female partner. Results showed a trend towards increased HIV transmission from men to their female partners. This trend was more notable, although still not statistically significant, when the men resumed sex before their wound had healed completely.

While this data is not new, its presentation at CROI gave an opportunity for discussion and analysis of its implications. Advocates stressed the necessity for all male circumcision programmes to directly address women’s increased vulnerability to infection by sex with a recently-circumcised, HIV-positive man.

UNAIDS Chief Scientific Adviser Dr Catherine Hankins said, “This underlines the importance of considering male circumcision as part of a comprehensive prevention package which includes couple counselling and post-surgery advice involving both partners. Couples should consider a mutual commitment to abstinence until the wound is healed completely.”

UNAIDS guidelines recommend that all men undergoing male circumcision should be clearly instructed and supported to abstain from sexual intercourse until certified wound healing, which normally can take up to six weeks, to avoid increasing the risk of both acquiring and transmitting HIV.

Most importantly, individuals must understand that male circumcision does not afford complete protection against HIV infection and that it must not replace other prevention strategies such as correct and consistent use of male and female condoms, reduction in the number of sexual partners, avoidance of penetration, and treatment of sexually transmitted infections.

Vaccines

Last September there was a disappointing failure in Merck’s adenovirus- based HIV vaccine candidate. The consensus from experts at CROI was that it was important for scientists to go back to the drawing board of basic science to get a better understanding of the workings of the virus and the responses of the human immune system. There was a call for increased investment into basic scientific research and less emphasis on expensive clinical trials, although clearly both are needed.

There is a growing acceptance that the search for the elusive HIV vaccine is set to continue for some time. This underscores the need to scale-up existing prevention and treatment strategies and highlights the importance of improving people’s access to sexual health information, access to HIV testing and counselling services and to male and female condoms.

Other interesting topics under discussion at CROI included improved screening for TB, ensuring adequate representation of women in HIV trials, aging and AIDS, and paediatric and adolescent HIV care.

It’s an unfortunate reality that all too often, the people most at risk and most in need of HIV prevention, treatment and care programmes are those least likely to have access to these services. For example it is estimated that fewer than one in 20 men who have sex with men (MSM) around the world have access to HIV prevention, treatment, and care services.

In a bid to scale-up action and stop the spread of AIDS among men who have sex with men, the Foundation for AIDS Research, amFAR has launched an initiative to support grassroots MSM organizations at the International AIDS Conference in Sydney.

The initiative, in addition to directly supporting grassroots organizations, will also advocate for more research on MSM issues and fund global advocacy efforts aimed at mobilizing funding from international donors, national governments, and others. The advocacy program will also focus on launching campaigns to end the stigma, discrimination, and violence that threatens the lives of MSM and fuels the spread of AIDS.

“Empowering MSM and other marginalized groups to protect themselves from HIV is one of the world’s most urgent health priorities,” said Dr. Peter Piot, Executive Director of UNAIDS.

This initiative is important as evidence and experience show that focusing AIDS programmes and services specifically on people who are most at risk leads to encouraging progress within the response and can help reduce stigma and discrimination.

In Bangladesh for example, successful advocacy from the Banhu Social Welfare Society, including networking and participation in governmental meetings, ensured the inclusion of issues relating to men who have sex with men in the five-year National AIDS Strategic Plan.

In Indonesia, the Aksi Stop AIDS and Family Health International programme worked with the Indonesian authorities to highlight the contribution that communities of men who have sex with men can make. These communities now regularly participate in consultations on AIDS-related issues with the Ministry of Health.

In many countries, however, prevention efforts are hindered by laws that criminalize male-male sex, making work with men who have sex with men difficult and impeding their contribution to the response to the epidemic. Where social, cultural and religious attitudes make the issue politically sensitive, politicians can be reluctant to support policies and programmes that might result in public criticism from community leaders and groups.

Lack of research about men who have sex with men including their behaviours and attitudes, and criminalization and stigmatization of and legal discrimination against these men, are significant barriers to implementing effective programmes.

“A quarter century into the epidemic, MSM in many countries still do not have even the basic tools to protect themselves against HIV,” said Kevin Frost, acting CEO of amfAR. “We must have the courage to stand side by side with the grassroots organizations on the front lines of this epidemic delivering services and demanding greater action from governments. With funding and support, these organizations can transform attitudes, change policy, and mobilize funding to reverse the spread of HIV among MSM.”

On 1 December 2006, UNAIDS joined with a broad range of UN and Thai partners to organize a World AIDS Day event with a difference.

As well as hosting a packed celebration event, Thailand captured international attention with an attempt to create the world’s longest chain of condoms.

And at the end of March, confirmation arrived—at 2,715 metres long, the condom chain sets a new Guinness World Record™.

The tying of the world’s longest chain of condoms was one of the events of the “Condom Chain of Life Festival”, a unique celebration of World AIDS Day, held at Lumpini Park in Bangkok. The festival was organized by the United Nations Educational, Scientific and Cultural Organization (UNESCO) Bangkok in collaboration with the Thai Red Cross, PLAN Thailand, UNAIDS and local NGOs as part of efforts to promote the acceptance of condoms, emphasize the need for safe sex, and encourage strengthening of national policies for comprehensive treatment, care and support for people living with and affected by HIV.

UNAIDS Special Representative Senator Mechai Viravaidya, well known for his groundbreaking HIV prevention efforts in Thailand, led the tying of the chain.

Here, UNAIDS Country Coordinator for Thailand, Patrick Brenny, tells (click on link below to listen to the interview) www.unaids.org about how the World Record attempt came about and its importance to the Thai AIDS response.

Experts from across the world are gathering this week in Montreux in Switzerland to review the results of recent trials establishing that male circumcision reduces by almost 60% the risk of men to acquire HIV during vaginal sex. These results announced in December 2006 and detailed in recent publications in The Lancet sparked interest and debate in the world of HIV. Is male circumcision as significant an advance as some of its proponents have claimed?

Dr Kim Dickson, from the HIV Department of the World Health Organization is a recognized and respected figure in the field of reproductive health and HIV. She currently coordinates the joint WHO/UNAIDS working group on male circumcision and HIV prevention as well as the Inter-agency Task Team on male circumcision and HIV prevention. She has kindly agreed to tell us more about the meeting and its expected outcomes.

Unaids.org: Dr Dickson, you coordinate the joint WHO/UNAIDS working group on male circumcision and HIV prevention. Can you tell us why WHO and UNAIDS are convening this meeting on male circumcision?

KD: When the US National Institutes of Health decided, in December 2006, to stop the two trials they were funding in Kenya and Uganda on male circumcision and HIV, it became clear that we needed to assess male circumcision as a potential public health intervention in the response to AIDS. The trials, as detailed in the results recently published in The Lancet, confirmed many previous observational studies which suggested that male circumcision significantly reduced the risk of men in acquiring HIV during vaginal sex.

It was important that the World Health Organization and the Joint United Nations Program on HIV/AIDS review the research results and consider what they mean for HIV prevention policy and programming in countries. It was decided to convene a meeting to bring around the table as many stakeholders as possible to look at and discuss many of the issues that male circumcision can raise, and, if possible, give guidance and recommendations for Member States and other stakeholders.

Unaids.org: How many participants are joining in this meeting and what do they represent?

KD: We invited the trials' investigators to present their methodology and their results. We also invited other scientists, from different disciplines such as social science, human rights and communications to ask the investigators questions which were not necessarily in the scope of their trials. We also have 16 representatives from Member States, and 11 from the civil society, including women’s health advocates and a representative from the Global Network of People Living with HIV, to present their own reading of the results and also to raise the issues that they face in their countries and in the context of their activities.

We paid special attention to invite people representing different positions. Last, but not least, we also have eight funding agencies and six implementing partners joining in the discussions. Overall, we are expecting almost 80 participants in Montreux. No need to say that we expect intense discussions that will touch upon many difficult issues.

Unaids.org: What do you expect as the outcomes of this meeting?

KD: The first and immediate outcome resides in the debate that is going to take place this week. This is the first time ever that such a wide range of stakeholders exchange views and discusses the consequences of male circumcision as an additional prevention method in the response to AIDS. At this stage, we cannot pre-empt the outcome. Maybe we will conclude the meeting with more questions than we began with- though I am hoping that at least some questions will be answered and that we will be able to make some recommendations.

The meeting will also identify what we need to do next in order to move forward. In any case, there will be a meeting report which we will make public shortly after the meeting.

Finally, I want to emphasize again and again that our objective is to examine male circumcision as an additional prevention method which should always be part of a comprehensive package which includes, among other elements, the correct and consistent use of male and female condoms, the delay in sexual debut and the reduction of sexual partners. The meeting will discuss how we can strengthen our communications so as not to undermine other prevention methods if we are to scale up male circumcision services.

If the United Nations moves forward with guidance to countries on male circumcision as a public health intervention for HIV prevention, it will be promoted as an ‘additional’ intervention to current HIV prevention packages; not as an alternative. People must understand that male circumcision does not provide complete prevention and they should be encouraged to use more than one of the prevention choices available to them.

In the final part of a special series on the issue of male circumcision and its links to the reduction of HIV acquisition, www.unaids.org discusses expected upcoming action and developments from the United Nations on male circumcision through a special interview with UNAIDS Chief Scientist, Dr Catherine Hankins

From 6-8 March 2007, public health experts from the World Health Organization, UNAIDS and other partner organizations will gather in Montreux, Switzerland, to discuss the topical and often thorny issue of male circumcision and its links to HIV prevention, and to define future United Nations guidance to countries on the policy and programming implications of recent research findings.

As the consultation approaches, UNAIDS’ Chief Scientific Adviser, Dr Catherine Hankins gives a preview of the different issues that may be raised, and an insight into considerations for potential outcomes and action for the United Nations.

Unaids.org: Dr Hankins, you’ve been involved in the issue of male circumcision and its impact on HIV for many years—how do the current findings corroborate scientists’ claims that there is a link between circumcision and reduced HIV infections?

CH: For many years, researchers and scientists have noted that parts of Sub-Saharan Africa where circumcision is common, such as countries in West Africa, have much lower levels of HIV infection, while those in southern Africa, where circumcision is rare, have the highest. Before the availability of data from these three randomised controlled trials, multiple observational studies indicated that male circumcision carried with it a reduced risk of HIV infection. The latest findings from the three trials indicate that male circumcision provides a protective benefit against HIV infection of 50% to 60%

A further trial, led by researchers at Johns Hopkins University, to assess the impact of male circumcision on the risk of HIV transmission to female partners is currently under way in Uganda, with results expected in 2008.

Unaids.org: What is the United Nations doing about this latest evidence that male circumcision reduces risk of HIV acquisition?

CH: Although these results demonstrate that male circumcision reduces the risk of men becoming infected with HIV, the United Nations agencies involved in this work absolutely underline that it does not provide complete protection against HIV infection- we need to make sure that men and women understand that circumcised men can still become infected with the virus and if HIV-positive, can infect their sexual partners.

Next week, WHO, the UNAIDS Secretariat and their partners will review the trial findings in detail at a consultation which will define specific recommendations for expanding and/or promoting male circumcision. These recommendations will need to take into account a number of key issues including the cultural and human rights considerations associated with promoting male circumcision; the risk of complications from the procedure performed in various settings; the potential of male circumcision to undermine or to work in synergy with existing protective behaviours and prevention strategies that reduce the risk of HIV infection; and the financial and human resource implications of male circumcision in different service delivery settings.

In order to support countries or institutions that decide to scale up male circumcision services, with our partners we are developing technical guidance on ethical, rights-based, clinical and programmatic approaches to male circumcision. We are also developing guidance on training, standard setting and certification procedures.

Unaids.org: What are some of the key concerns about increasing male circumcision practice that will be discussed at the consultation?

CH: A number of thorny issues arise related to promoting male circumcision as a public health intervention for HIV prevention. Adult male circumcision has a higher risk of adverse effects than infant male circumcision, and should be undertaken by trained health workers in safe, adequately equipped and sanitary conditions with appropriate pre and post-surgical counselling and follow-up. There is a real need to ensure that male circumcision interventions for health benefits are differentiated from female genital mutilation which the UN opposes and is considered to have no health benefits and potentially severe consequences for women and girls.

We also have to take into account the cultural issues- within cultures and faith traditions in which male circumcision is not considered acceptable, promoting it may or may not prove challenging. Without question, we absolutely have to ensure that men and women are aware that male circumcision is not a ‘magic bullet’- it doesn’t provide total protection and it doesn’t mean people can stop taking the safe sex precautions they were already using, such as use of male or female condoms, delaying sexual debut, avoiding penetrative sex and decreasing the number of sexual partners. We must continue to promote combination prevention and ensure that male circumcision is perceived as an additional benefit but one that should be in combination with other strategies to prevent sexual transmission of HIV. We don’t want increased risk behaviour to offset the benefits.

If the United Nations moves forward with guidance to countries on male circumcision as a public health intervention for HIV prevention, it will be promoted as an ‘additional’ intervention to current HIV prevention packages; not an alternative.

Effective communication on male circumcision will be critical and will be an opportunity to reinforce messages on the need for a comprehensive approach to prevention that encourages people to use more than one of the prevention choices available to them.

Unaids.org: Would male circumcision be part of the HIV prevention response for all settings?

Countries with high HIV prevalence and low male circumcision levels may be among the first to consider the potential for male circumcision to play a role in their HIV prevention programming. Other countries may decide to provide male circumcision services to particular populations who could benefit from the additional protection that male circumcision can afford.

The UN and its partners are fully aware that male circumcision may raise cultural and religious issues – it should never be imposed and, if it is promoted, must be done in a culturally acceptable manner in settings where it is not traditionally practised.

CH: Like all types of surgery, circumcision is not without risk. Circumcision by unqualified individuals under unsanitary conditions with poorly maintained or sub-optional equipment can lead to serious, immediate and long-term complications, or even death. Where health professionals have been trained and equipped to perform safe male circumcisions, however, the rate of post-operative complications is less than 5% and the large majority of these resolve with simple, appropriate post-operative care.

Anecdotal accounts of serious complications, including penile amputation and death after male circumcision in traditional settings have been reported. It is difficult to give overall figures for adverse events in all settings, in part because well-documented studies of complication rates in low-and-middle income countries are rare.

Unaids.org: Is there a need to improve male circumcision practices?

CH: Absolutely. Action is required now to improve circumcision practices in many regions, and to ensure that health-care providers and the public have up-to-date information on the health risks and benefits of male circumcision. Many boys and men wishing to be circumcised do not have access to safe circumcision services nor to post-circumcision care if they do suffer from complications. Regardless of the HIV prevention benefits, it is now increasingly important to make existing practices safer. Where circumcision is legal, authorities need to ensure that practitioners are properly trained and licensed to do this procedure. Monitoring should also be done to ensure that procedures are performed safely and that untrained practitioners do not continue to perform unsafe circumcisions.

Unaids.org: Does male circumcision raise human rights issues?

CH: Yes, as is the case with all medical and health procedures. In line with internationally accepted ethical and human rights principles, UNAIDS and WHO are of the view that no surgical intervention should be performed on anyone if it results in adverse outcomes in terms of health or the integrity of the body, and where there is no expectation of health benefit. Nor should any surgical intervention be performed on anyone without informed consent, or the consent of the parents or guardians when a child is not capable of providing consent.

As male circumcision involves surgery and removal of a part of the body, it should only be performed under these conditions: a) participants are fully informed of the possible risks and benefits of the procedure; b) participants give their fully informed consent; and c) the procedure can be performed under fully hygienic conditions by adequately trained and well equipped practitioners with appropriate post-operative follow-up.

Unaids.org: What effect on the HIV epidemic might we expect if male circumcision were commonly practised where it currently is not?

An international group of experts have carried out a mathematical modelling exercise on the impact on HIV incidence of a programme of universal male circumcision in sub-Saharan Africa, assuming the programme worked as it had in Orange Farm, South Africa and that all men would be circumcised within 10 years. The model predicts that 5.7 million infections and 3 million deaths would be prevented over 20 years among both men and women. There are many unknowns within this model but it does predict that male circumcision would provide a significant, potential benefit, similar to a partially effective vaccine. Importantly though, the model also shows that male circumcision alone cannot eliminate the HIV epidemic in sub-Saharan Africa.

Unaids.org: Could male circumcision eliminate the risk of HIV infection?

CH: No. Male circumcision alone certainly does not prevent men from becoming infected with HIV. Nor does it prevent women from being infected with HIV by men who have been circumcised. Circumcision needs to be seen as one of the range of methods to reduce the risk of HIV—including avoidance of penetrative sex, delaying sexual debut, reduction in the number of sexual partners, and correct and consistent male or female condom use. Male circumcision reduces the risk of HIV infection during vaginal intercourse, but is unknown whether it would have an effect on other routes of sexual HIV transmission: the receptive partner in anal intercourse may not have a reduced risk due to the circumcision status of his or her partner and, if male, will not have a reduced risk due to his own circumcision status. It is also not known whether male circumcision reduces the risk of HIV infection for the insertive partner during anal intercourse. Male circumcision has no effect in the case of HIV transmission through injecting drug use.

Unaids.org: Given all these considerations, is it likely the UN will recommending that adult men become circumcised as a way to protect themselves from HIV?

CH: This is what will be discussed at the consultation, and the partners expect to release information about the discussions and possible next steps at the end of the week’s meeting.

In any and all cases for future direction and action, the UN and its partners will certainly underline that male circumcision does not provide complete protection from HIV. It should therefore never replace other known effective preventive methods, such as delay in onset of sexual activity, abstinence from penetrative sex, correct and consistent use of condoms, and reductions in the number of sexual partners.

It’s very important that we stress that circumcised men, if HIV positive, can still infect their sexual partners if they do not use condoms during penetrative sexual intercourse.

In the second of a special three-part series on the issue of male circumcision and its links to the reduction of HIV acquisition, unaids.org considers current research findings.

It’s a subject that hits headlines, fuels discussions, sparks debate and causes some of the men in the room to wince and cross their legs. Male circumcision and its links to HIV is one of the most talked about issues within the AIDS response over the last years, with latest research findings driving potential change in the way male circumcision is practiced and implemented for the future in relation to HIV prevention.

In scientific circles, the perceived links between male circumcision and HIV infection are nothing new. For years, AIDS researchers have observed that many African tribes that circumcise boys or young men had lower HIV rates than those that do not, and that Africa's Islamic nations, where circumcision is near universal, had far fewer AIDS cases than predominantly Christian ones.

Now, trials in Kenya, Uganda and South Africa have all shown that male circumcision significantly reduces a man’s risk of acquiring HIV. The three sets of trials have shown circumcised men are up 50 to 60% less likely to acquire HIV during heterosexual intercourse.

Research findings

The first research proof came in 2005, when a study in South Africa, supported by the French agence nationale de recherches sur le sida (ANRS) and known as the 'Orange Farm Intervention Trial', was stopped early in the face of evidence that the men who had been randomly assigned to be circumcised were getting 60% fewer HIV infections than the men assigned to the control group.

In December 2006, on the recommendation of their Data and Safety Monitoring Board (DSMB), two similar studies in Uganda and Kenya were halted early by the United States National Institutes of Health (NIH) because the interim results showed a significant effect of male circumcision in preventing HIV acquisition in men.

The trial carried out in Kisumu, Kenya by researchers from the University of Nairobi, University of Illinois at Chicago, the University of Manitoba, and RTI International involving 2,784 men aged 18 to 24 showed a 53% reduction of HIV infections in circumcised men compared to uncircumcised men.

In Uganda, the trial, carried out in Rakai by researchers from Makerere University, the Uganda Virus Research Institute, Johns Hopkins University, and Columbia University New York, involved 4996 men aged 15 to 49 years old and showed that adult male circumcision reduced by 51% the risk of becoming infected with HIV.

Dr. Anthony Fauci, director of the NIH's National Institute of Allergy and Infectious Diseases, said the institute ended both trials early and offered circumcision to all men involved in them. The trials began in 2005 and were due to go until mid-2007.

The biology

Male circumcision involves the surgical removal of the foreskin, the tissue covering the head of the penis. Previous research shows that removing the foreskin is associated with a variety of health benefits including lower rates of urinary tract infections in male infants who are circumcised and reduced risk of certain inflammations and health problems associated with the foreskin.

Scientists say male circumcision probably reduces the risk of HIV infection because it removes tissue in the foreskin that is particularly vulnerable to the virus, and because the area under the foreskin is easily scratched or torn during sex. “Uncircumcised men may also be more vulnerable to sexually transmitted diseases, which in turn increase the risk of contracting HIV, because the region under the foreskin provides a moist, dark place in which germs can thrive,” said UNAIDS Chief Scientific Adviser, Dr Catherine Hankins.

No ‘magic bullet’

The results of the trials in South Africa, Uganda and Kenya indicate that in certain settings, adult male circumcision could become an important addition to an HIV prevention strategy for men. “The trials indicate that male circumcision can lower both an individual's risk of infection and hopefully the rate of HIV spread through the community," NIH’s Dr Fauci said.

But experts— including the United Nations bodies working on the issue—caution that circumcision is no cure-all. Male circumcision does not provide complete protection against HIV infection; it only lessens the chances that a man will acquire the virus.

Circumcision is "not a magic bullet, but a potentially important intervention," said Dr. Kevin M. De Cock, director of the World Health Organization’s AIDS department.

“Men and women must understand that circumcised men can still become infected with the virus and if HIV-positive, can infect their sexual partners,” said UNAIDS’ Dr Hankins

“ Male circumcision should never replace other known effective prevention methods and should always be considered as part of a comprehensive HIV 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 abstaining from penetrative sex”, she said.

Safety, sanitation and communication

To ensure safe and clean operations, male circumcision should only be performed by well-trained practitioners in sanitary settings under conditions of informed consent, confidentiality, proper counseling and safety. “If male circumcision is to be promoted, this should be done in a culturally appropriate manner and people should be provided sufficient and correct information on HIV prevention to prevent them from developing a false sense of security and engaging in risky behavior,” said Dr Hankins.

These considerations and others in relation to the AIDS response, including the fact that male circumcision has the potential to be an expensive intervention, that more research is needed to address whether male circumcision reduces risk of transmitting HIV-particularly for female partners, and the different ethical and human rights issues raised by male circumcision, will form discussions of the United Nations consultation on male circumcision that will take place in Geneva from 5 March. Here, WHO, the UNAIDS Secretariat and their partners will review the detailed trial findings and will, if deemed appropriate, then define specific policy recommendations for expanding and/or promoting male circumcision.

“Male circumcision is a complicated issue which involves sometimes difficult discussion on issues of culture, tradition, religion, ethnicity, human rights and gender. The consultation will provide an excellent arena for moving the discussion and policy forward within the United Nations,” said Dr Hankins.

Male Circumcision: context, criteria and culture (Part 1)
Male Circumcision and HIV: the here and now (Part 2)
Moving forwards: UN policy and action on male circumcision (Part 3) 

With male circumcision and its links to HIV acquisition hitting the headlines and sparking debates around the world, in the first of a special three-part series on the issue, www.unaids.org takes a closer look at the historical, traditional and increasingly social reasons behind the practice of male circumcision across the world.

Male circumcision is one of the oldest and most common surgical procedures known, traditionally undertaken as a mark of cultural identity or religious importance.

Historically, male circumcision was practised among ancient Semitic people including Egyptians and those of Jewish faith, with the earliest records depicting circumcision on Egyptian temple and wall paintings dating from around 2300 BC.

With advances in surgery in the 19th century, and increased mobility in the 20th century, the procedure was introduced into some previously non-circumcising cultures for both health-related and social reasons.

According to current estimations, approximately 30% of all males across the world— representing a total of approximately 670 million men — are circumcised. Of this number, about 68% are of Islamic faith, less than 1% of Jewish faith, and 13% are non-Muslim, non-Jewish Americans.

“With the recent findings that male circumcision significantly reduces a man’s risk of acquiring HIV the practice is receiving renewed interest as the world looks to understand what this will mean for HIV prevention,” said UNAIDS Chief Scientific Adviser, Dr Catherine Hankins. “Looking at the determinants of male circumcision, and the acceptability of male circumcision in non-circumcising societies give a better picture of how to take the latest research findings forward.”

Religious practice

In the Jewish religion, male infants are traditionally circumcised on their eighth day of life, providing there is no medical contraindication. The justification, in the Jewish holy book the Torah, is that a covenant was made between Abraham and God, the outward sign of which is circumcision for all Jewish males. The Torah states: “ This is my covenant, which ye shall keep, between me and you and thy seed after thee: every male among you shall be circumcised " (Genesis 17:10). Male circumcision continues to be almost universally practiced among Jewish people.

Islam is the largest religious group to practice male circumcision. As an Abrahamic faith, Islamic people practice circumcision as a confirmation of their relationship with God, and the practice is also known as ‘tahera’, meaning purification. With the global spread of Islam from the 7th century AD, male circumcision was widely adopted among previously non-circumcising peoples. There is no clearly prescribed age for circumcision in Islam, although the prophet Muhammad recommended it be carried out at an early age and reportedly circumcised his sons on the seventh day after birth. Many Muslims perform the rite on this day, although a Muslim may be circumcised at any age between birth and puberty.

The Coptic Christians in Egypt and the Ethiopian Orthodox Christians— two of the oldest surviving forms of Christianity— retain many of the features of early Christianity, including male circumcision. Circumcision is not prescribed in other forms of Christianity. In the New Testament, St. Paul wrote: "in Christ Jesus neither circumcision nor uncircumcision count for anything" (Galatians 5:6) and a Papal Bull issued in 1442 by the Roman Catholic Church stated that male circumcision was unnecessary: “Therefore it strictly orders all who glory in the name of Christian, not to practise circumcision either before or after baptism, since whether or not they place their hope in it, it cannot possibly be observed without loss of eternal salvation,” it stated. Focus group discussions on male circumcision in sub-Saharan Africa found no clear consensus on compatibility of male circumcision with Christian beliefs. Some Christian churches in South Africa oppose the practice, viewing it as a pagan ritual, while others, including the Nomiya church in Kenya, require circumcision for membership and participants in focus group discussions in Zambia and Malawi mentioned similar beliefs that Christians should practice circumcision since Jesus was circumcised and the Bible teaches the practice.

Circumcision has been practiced for non-religious reasons for many thousands of years in sub-Saharan Africa, and in many ethnic groups around the world, including aboriginal Australasians, the Aztecs and Mayans in the Americas, inhabitants of the Philippines and Eastern Indonesia and of various Pacific Islands, including Fiji and the Polynesian islands.

In the majority of these cultures, circumcision is an integral part of a rite-of-passage to manhood, although originally it may have been a test of bravery and endurance. “Circumcision is also associated with factors such as masculinity, social cohesion with boys of the same age who become circumcised at the same time, self-identity and spirituality,” Dr Hankins explained.

The ethnographer Arnold Van Gennep in his 1909 work ‘The Rites of Passage’ , describes various initiation rites which are present in many circumcision rituals. These include a three stage process: separation from normal society; a period during which the neophyte undergoes transformation; and finally reintegration into society in a new social role.

“A psychological explanation for this process is that ambiguity in social roles creates tension, and a symbolic reclassification is necessary as individuals approach the transition from being defined as a child to being defined as an adult. This is supported by the fact that many rituals attach specific meaning to circumcision which justify its purpose within this context,” said Dr Hankins. For example, certain ethnic groups including the Dogon and Dowayo of West Africa, and the Xhosa of South Africa view the foreskin as the feminine element of the penis, the removal of which (along with passing certain tests) makes a man of the child.

Tradition plays a major part for many ethnic groups. Among ethnic groups of Bendel State in southern Nigeria, 43% of men stated that their motivation for circumcision was to maintain their tradition. In some settings where circumcision is the norm, there is discrimination against non-circumcised men. For the Lunda and Luvale tribes in Zambia, or the Bagisu in Uganda, it is unacceptable to remain uncircumcised, to the extent that forced circumcisions of older boys are not uncommon. Among the Xhosa in South Africa, men who have not been circumcised can suffer extreme forms of punishment, including bullying and beatings.

Circumcision as a social statement

Social reasons behind male circumcision are becoming ever more common. “The desire to conform is an important motivation for circumcision in places where the majority of boys are circumcised,” said Dr Hankins.

A survey in Denver, US where circumcision occurs shortly after birth, found that parents, especially fathers, of newborn boys cited social reasons as the main determinant for choosing circumcision (e.g. not wanting the son to ‘look different’ from the father).

In the Philippines, where circumcision is almost universal and typically occurs at age 10-14, a survey of boys found two-thirds of those surveyed choosing to be circumcised simply ‘to avoid being uncircumcised’, and 41% stating that it was ‘part of the tradition’. Social concerns were also the primary reason for circumcision in South Korea with 61% of respondents in one study believing they would be ridiculed by their peer group unless they were circumcised.

The desire to ‘belong’ is also likely to be the main factor behind the high rate of adult male circumcisions among immigrants to Israel from non-circumcising countries (predominantly the former Soviet Union).

In a number of countries, socio-economic factors also influence circumcision prevalence, especially in countries with more recent uptake of the practice such as English-speaking industrialised countries. When male circumcision was first practised in the United Kingdom in the late 19th and early 20th century, it was most prevalent among the upper classes. In the US, a review of 4.7 million newborn male circumcisions nationwide between 1988 and 2000 also found a significant association with private insurance and higher socioeconomic status.

Perceived health and sexual benefits

In more recent times, perceptions of improved hygiene and lower risk of infections through male circumcision have driven the spread of circumcision practices in the industrialised world.

In a study of US newborns in 1983, mothers cited hygiene as the most important determinant of choosing to circumcise their sons, and in Ghana, male circumcision is seen as cleansing the boy after birth. Improved hygiene was also cited by 23% of 110 boys circumcised in the Philippines and in South Korea, the principal reasons given for circumcision were ‘to improve penile hygiene’ (71% and 78% respectively) and to prevent conditions such as penile cancer, sexually transmitted diseases and HIV. In Nyanza Province, Kenya, 96% of uncircumcised men and 97% of women irrespective of their preference for male circumcision stated their opinion that it was easier for circumcised men to maintain cleanliness.

Perceived improvement of sexual attraction and performance can also motivate circumcision. In a survey of boys in the Philippines, 11% stated that a determinant of becoming circumcised was that women like to have sexual intercourse with a circumcised man, and 18% of men in the study in South Korea stated that circumcision could enhance sexual pleasure. In Nyanza Province, Kenya, 55% of uncircumcised men believed that women enjoyed sex more with circumcised men. Similarly, the majority of women believe that women enjoyed sex more with circumcised men, even though it is likely that most women in Nyanza have never experienced sexual relations with a circumcised man. In northwest Tanzania, younger men associated circumcision with enhanced sexual pleasure for both men and women, and in Westonaria district, South Africa, about half of men said that women preferred circumcised partners.

Expected increase in demand

Global estimates in 2006 suggest that about 30% of males — representing a total of approximately 670 million men — are circumcised.

With latest research findings suggesting that circumcised men have a significantly lower risk of becoming infected with HIV, demand for safe, affordable, male circumcision is expected to increase rapidly.

“Since male circumcision is now shown to be effective in reducing the risk of HIV acquisition, care must be taken to ensure that men and women understand that the procedure does not provide complete protection against HIV infection,” said Dr Hankins, underlining that these issues will be discussed at the “ Male Circumcision and HIV Prevention Research - Policy and Programme Implications” International Consultation to be held in Montreux from 6-8 March 2007. “Male circumcision must be considered as just one element of a comprehensive HIV prevention package that includes the correct and consistent use of male or female condoms, reductions in the number of sexual partners, delaying the onset of sexual relations and abstaining from penetrative sex. Just as combination treatment is the best strategy to treat HIV, combination prevention is the best strategy to avoid acquiring or transmitting HIV”, she added.

“Action is also required to improve the safety of circumcision practices in many countries and to ensure that health care providers and the public have up-to-date information on the health risks and benefits of male circumcision,” she said.

Links:

Read Part 2 - Male Circumcision and HIV: the here and now
Read Part 3 - Moving forward: UN policy and action on male circumcision

Male circumcision is one of the world’s oldest surgical practices; carvings depicting circumcisions have been found in ancient Egyptian temples dating as far back as 2300 BC.

In recent months, the issue of male circumcision and its links to the transmission of HIV has hit the headlines and sparked debates across the world. Trials in Kenya, Uganda and South Africa have now all shown that male circumcision significantly reduces a man’s risk of acquiring HIV.

As UNAIDS, the World Health Organization and other partners prepare to look at how to take these findings forward, in terms of UN guidance to countries on policy and programming, at a consultation to be held in Geneva from 5-8 March 2007, www.unaids.org takes an in-depth look at the issue of male circumcision in a special three-part series. Where did male circumcision originate, who practices it and why? These questions and others relating to the history and determinants of male circumcision will be considered in part one of the series – ‘Male Circumcision: context, criteria and culture’, published on Monday 26 February. On Wednesday 28 February, part two –‘Male circumcision and HIV: The here and now’ will summarize current research findings on male circumcision and HIV acquisition. Part three, to be published on Friday 2 March will discuss future action and developments from the United Nations and feature a special interview with UNAIDS Chief Scientific Adviser, Dr Catherine Hankins.

Male Circumcision: context, criteria and culture (Part 1)
Male Circumcision and HIV: the here and now (Part 2)
Moving forwards: UN policy and action on male circumcision (Part 3)