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Male circumcision for HIV prevention: current evidence and implementation in sub-Saharan Africa

Richard G Wamai1*, Brian J Morris2, Stefan A Bailis3, David Sokal4, Jeffrey D Klausner5, Ross Appleton6, Nelson Sewankambo7, David A Cooper8, John Bongaarts9, Guy de Bruyn10, Alex D Wodak11 and Joya Banerjee12

Author affiliations

1 Department of African-American Studies, Northeastern University, Boston, MA, USA

2 School of Medical Sciences, University of Sydney, Australia

3 Research & Education Association on Circumcision Health Effects, Bloomington, MN, USA

4 Behavioral and Biomedical Research, Family Health International, Research Triangle Park, NC, USA

5 Department of Medicine, University of California, San Francisco Department of Public Health, USA

6 College of Professional Studies, Northeastern University, Boston, MA, USA

7 Makerere University College of Health Sciences, Kampala, Uganda

8 Kirby Institute, St Vincents Hospital and University of New South Wales Sydney, Australia

9 Population Council, One Dag Hammarskjold Plaza, New York, NY, USA

10 Perinatal HIV Research Unit, New Nurses Home, Chris Hani Baragwanath Hospital, Johannesburg, South Africa

11 Alcohol & Drug Unit, St Vincent's Hospital, Sydney, Australia

12 Global Youth Coalition on HIV/AIDS, Pretoria, South Africa

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Citation and License

Journal of the International AIDS Society 2011, 14:49  doi:10.1186/1758-2652-14-49


The electronic version of this article is the complete one and can be found online at: http://www.jiasociety.org/content/14/1/49


Received:1 March 2011
Accepted:20 October 2011
Published:20 October 2011

© 2011 Wamai et al; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Heterosexual exposure accounts for most HIV transmission in sub-Saharan Africa, and this mode, as a proportion of new infections, is escalating globally. The scientific evidence accumulated over more than 20 years shows that among the strategies advocated during this period for HIV prevention, male circumcision is one of, if not, the most efficacious epidemiologically, as well as cost-wise. Despite this, and recommendation of the procedure by global policy makers, national implementation has been slow. Additionally, some are not convinced of the protective effect of male circumcision and there are also reports, unsupported by evidence, that non-sex-related drivers play a major role in HIV transmission in sub-Saharan Africa. Here, we provide a critical evaluation of the state of the current evidence for male circumcision in reducing HIV infection in light of established transmission drivers, provide an update on programmes now in place in this region, and explain why policies based on established scientific evidence should be prioritized. We conclude that the evidence supports the need to accelerate the implementation of medical male circumcision programmes for HIV prevention in generalized heterosexual epidemics, as well as in countering the growing heterosexual transmission in countries where HIV prevalence is presently low.

Review

Implementation of male circumcision (MC) for HIV prevention in sub-Saharan Africa remains disappointingly slow despite its proven efficacy of greater than 60% based on the results of three randomized controlled trials (RCTs) conducted in the region [1-3]. These data received support from a Cochrane review [4] and confirm more than two decades of data from observational studies [5]. An as-treated meta-analysis for the 15 observational studies that adjusted for potential confounders gave a summary risk ratio indicating a protective effect of 65% that was identical to the initial findings from the three RCTs [6,7]. Another meta-analysis of the RCT data reported a relative risk reduction of 56% [8].

In a meta-analysis of 13 studies, 85% of which were from sub-Saharan Africa, a 58% protective effect was noted (53% for general populations and 69% for high-risk populations) [9]. In this report, protection was 57% for the RCTs and 61% for observational studies (cohort studies 71% and case control 46%). In addition, if MC status was ascertained by self-report, the protective effect was 45%, but if by direct genital examination in the clinic, it was 65%. These authors pointed out that the current data on MC satisfy six of the nine criteria of causality as outlined by Sir AB Hill, namely strength of association, consistency, temporality, coherence, biological plausibility and experiment [10].

With these definitive results, key international health bodies [11,12] and numerous governments of countries most affected [13,14] have formulated affirmative policies on MC for HIV prevention. There is now a consensus among most experts in the HIV/AIDS scientific community that MC, although not a "magic bullet", is a critical component in the "tool box" of HIV prevention approaches. Crucial to the effectiveness of MC policy is an understanding of how effective MC will be in HIV reduction, and as a corollary to this, the level of importance that heterosexual transmission plays in overall HIV transmission in a population.

Historically, transmission of HIV has been attributed to four main modes: sexual intercourse, transfusion, parenteral and perinatal acquisition [15]. In light of this, multiple types of intervention strategies (behavioural, structural and biomedical) have been advocated [16]. While scientists seek to provide the evidence base, public policy makers must evaluate logically where the preponderance of evidence lies, and make correct decisions based on a reasonable assessment of such evidence [17]. Urgent calls have been made by experts and advocates to accelerate HIV prevention scale up in line with the prevention principles [18,19]. However, in some instances skepticism about the evidence has led to hesitation, delays and inaction, leading to misery and, as in South Africa, needless death for hundreds of thousands from failure to expeditiously implement programmes that work [20].

In the sub-Saharan African setting, the established convention is that heterosexual transmission is the primary driver for the HIV epidemic. Recently, however, some have argued that current HIV prevention interventions are based on "insufficient information" on modes of transmission and what works [21]. We agree that there is a need to continually evaluate and update knowledge on HIV transmission and what works in prevention so as to better inform and reinforce policy making and implementation. Therefore, in reinforcing the policy imperative for MC as a proven method for prevention of heterosexual HIV transmission, we first review the state of knowledge on modes of HIV transmission in sub-Saharan Africa. We then assess the strength of current evidence for MC in protecting against HIV infection, before analyzing current MC implementation programmes in the region. Finally, we highlight some of the outstanding issues and call for an acceleration in MC implementation as an evidence-based strategy to stem the HIV/AIDS epidemic.

What we know about the drivers of HIV infection in sub-Saharan Africa

According to the latest Joint United Nations Programme on HIV/AIDS (UNAIDS) epidemic update report, of the 33.3 million people living with HIV/AIDS worldwide at the end of 2009, 92.5% were adults [22]. About half were women and 67.6% live in sub-Saharan Africa, where women comprise about 60% of cases [22]. Of total infections globally, 2.5 million (approximately 7.5% of the total) were in children (aged younger than 15 years), of whom 92% live in sub-Saharan Africa where they comprise 10% of all cases [22]. Although some children younger than 15 are sexually active, the prevalence estimates show that 92.5% of cases globally and 90% in sub-Saharan Africa are in the adult population [22].

While this in itself does not necessarily show association with sexual activity, the preponderance of infection in adults can only be explained by adult-specific factors not affecting children. HIV distribution by sex and across age groups are clearly consistent with sexual behaviour as the main mode of transmission, as shown by the significant and sudden increase in HIV in those older than 15 years [22,23].

Consistent evidence for a major role of sexual intercourse in transmission of HIV has been provided by numerous modelling studies [24-28] and ecological observations, published by the World Health Organization (WHO) and UNAIDS in their annual report [22], as well as in national estimates [29]. These data are collected according to global norms [30,31] whose methods are continually refined [32-35].

The effect of sexual transmission likely lie in context-specific factors confounding host and agent alike. These include stage of the disease, associated viral load, other biological factors [24,36-40], as well as the socio-economic and policy context [20,41]. Credible research shows that the key initial drivers of the sexual transmission were a synergistic relationship between promiscuous practices, coupled with individual-level biological factors, namely sexually transmitted infections (STIs) (in particular, genital ulcer disease, syphilis and HSV-2) and lack of MC [40-44]. These factors also help explain the differences in rate of spread across the continent [42,45].

Among these, the role of multiple and concurrent partnerships (unstructured casual sex and polygyny) is well documented in many sub-Saharan Africa countries [46-51]. This is demonstrated, for example, in one of the most detailed studies, involving 179 focus groups and 116 in-depth interviews with diverse groups of people (male/female, young/old, urban/rural) in typical day-to-day settings in 10 countries of southern Africa that have high generalized HIV epidemics [52]. Modelling and network theory reveal dynamics of exposure [53,54]. Nevertheless, there is conflicting evidence on the extent to which multiple and concurrent partnerships drives the epidemic, as shown in recent assessments of the existing literature by Lurie and Rosenthal [55] and Sawers and Stillwaggon [56], as well as a debate hosted on 27 October 2010 by the United States Agency for International Development (USAID) and the World Bank among opposing sides [57].

While heterosexual behaviour plays a leading role in HIV transmission in sub-Saharan Africa, it is fair to ask what proportion of infections is from non-sexual drivers. These include: unsafe injections in medical and non-medical settings [58,59], injecting drug use and blood transfusion [60-62], mother to child transmission [22,61,63,64], men who have sex with men (MSM) [65,66] and cultural practices [67,68], such as unsafe traditional MC and female genital cutting [69-72]. While some argue that these play a significant role in sub-Saharan Africa [21,68,73,74], such evidence is largely circumstantial [62,75] and the level of such exposures are altogether too low to fuel a generalized epidemic [75-77]. One crucial illustration of this comes from a modelling approach in use since 2003 [61], namely the Modes of Transmission (MoT) approach. Developed by the UNAIDS Reference Group to help country-level policy makers respond to the epidemic and prioritize interventions, the MoT approach provides a robust means for estimating patterns of adult HIV transmission through different routes [61].

To date, MoT analyses have been conducted in Kenya [61], Lesotho [78], Swaziland [79], Uganda [80] and Zambia [81]. They show that sexual behaviour accounts for 94.1%, 97.0%, 94.0%, 99.6% and 99.8% of new infections, in each respective country, with the categories of multiple partnerships and partners of multiple partnerships contributing more than half of all cases in Lesotho and Zambia (Table 1). On the other hand, the population of MSM in sub-Saharan Africa is not known, partly due to laws prohibiting this behaviour in most countries, although HIV prevalence in MSM is, however, high [65]. A systematic review estimated that the MSM route makes an approximately 15.7% contribution to HIV prevalence in sub-Saharan Africa [82]. In one MSM cohort, in Mombasa, Kenya, HIV prevalence was 43% in men reporting exclusive MSM relations compared with 12% in men reporting sex with both men and women [83].

Table 1. Incident HIV infections by modes of transmission in five sub-Saharan Africa countries

In contrast, in Kenyan, Ugandan and Zambian studies, infections arising from blood transfusion were insignificant (Table 1). Furthermore, a review of Demographic and Health Surveys data from 10 countries indicated that although having had a blood transfusion increases risk of HIV infection among women (but not men) in Cameroon and Uganda, blood transfusions are rare [62]. While non-sexual routes are relatively minor, they merit continued monitoring [21,74,84]. Nonetheless, at present, evidence-based means of reducing heterosexual transmission should be prioritized [85]. One of these is male circumcision.

Efficacy of male circumcision for HIV prevention: an update on the evidence

As one of the oldest surgical procedures known to humankind and the most widely practiced surgery worldwide, male circumcision has served religious, socio-cultural and health purposes [69,86-88]. Since the suggestion in the 1980s that MC might prevent HIV infection [89-91], numerous ecological, case-control and cohort studies, reviews, systematic reviews and meta-analyses have established that MC significantly reduces the risk of heterosexual HIV infection [6-9,69,92-94]. The meta-analysis by Weiss et al of 27 observational studies to the late 1990s showed a reduced risk in 21 studies [7]. In 15 studies that adjusted for confounding factors, adjusted relative risk reduction was 0.42 (95% CI 0.34-0.54) [7]. A Cochrane systematic review in 2005 assessing the quality of 37 studies of MC and HIV noted that while the different methodologies showed varying results, the protective effect of MC was supported consistently [93].

In 2005 and 2007, the efficacy of MC in HIV prevention was verified beyond reasonable doubt by results from three large RCTs, the gold standard of epidemiological research, these being conducted in South Africa, Kenya and Uganda [1-3]. Acceptance by the international health community quickly followed [11-14]. In 2009, the Cochrane committee concluded that MC for HIV prevention was supported and no further trials were required [4]. More recently, a systematic review of 37 late-phase RCTs of various HIV prevention interventions found MC to have a stronger efficacy in preventing HIV infection than vaccines, microbicides and treatment of STIs [95]. An important development in MC documentation has been the initiation by UNAIDS, WHO and others of an online resource centre [96].

Research on acceptability of MC at the population level in sub-Saharan Africa countries in 14 studies in nine countries showed varied results, but was generally high among men and women [97,98]. Continued assessment of impacts, challenges and opportunities [99,100] support the urgency of accelerating the implementation of MC for HIV prevention [101,102]. In 2010, the US-based Center for Global Health Policy called for "aggressive scale up" of MC based on the evidence for its ability to prevent HIV infection [103]. The quality of the evidence supporting MC is "conclusive" [7], making MC a sound recommendation for public health [104]. Such evidence calls for skepticism to be dismissed [17].

Biological mechanism of male circumcision in mediating HIV infection

Several suggestions have been made to explain the vulnerability of the foreskin to HIV infection. The inner epithelium of the foreskin is mucosal, has been found to lack protective keratin and to contain Langerhans cells and T cells that express the HIV receptor, CD4 [87,105-109]. In an early study, HIV was taken up readily by the inner, but not the outer foreskin epithelium in explant culture [106]. Nearly a decade later, Ganor and colleagues developed two new excellent models of the foreskin epithelium: an improved explant model and a 3D immuno-competent in vitro model [108]. Their human adult ex vivo foreskin explant model showed that Langerhans cells and dermal T cells in the less-keratinized inner foreskin have a significantly higher density than in the outer foreskin. When the foreskin was exposed to mononuclear cells highly infected with HIV, but not free HIV, virions were found in the epidermis of the inner foreskin within one hour, demonstrating that Langerhans cells can efficiently transfer HIV to T cells [108].

In another review, Ganor and Bomsel suggested that the main pathway for HIV entry was driven by molecular signals, such as chemokines [109]. Findings of no difference [110] in, or greater [111], keratin thickness of the outer versus the inner foreskin or in susceptibility to HIV [112] have been dismissed as products of postmortem changes and technical artifacts [109]. Foreskin aspects relevant to HIV infection include the skin surface area, the microbiologic environment, HIV-1-susceptible cells and tissue structure, although more research is needed to determine the relative contribution of each [113].

Besides the ease of infection by inner epithelial cells to HIV, HIV is suspected of infecting the body via tears in the fragile inner surface of the foreskin and frenulum, which are also susceptible to infection by other STIs [43,87,105]. STIs hamper the ability of langerin in Langerhans cells to protect against HIV [107]. Thus the vulnerability of the foreskin to HIV infection lends biological support to the extensive epidemiological evidence for the protection MC confers against HIV infection in men during heterosexual intercourse.

The relationship between MC and HIV: evidence and issues from population-based surveys

The highly acclaimed RCTs [1-3] would not have taken place had there not been extensive observational evidence in place already attesting to the ability of MC to prevent HIV transmission. Nevertheless, RCTs have been overvalued in medical studies and, by themselves, they yield insufficient evidence for policy and must be supplemented by observational evidence [5]. Population-based surveys, in particular, the Demographic and Health Survey (DHS) and the AIDS Indicator Survey, have been cited frequently because of the insights they provide into the patterning of HIV and MC in sub-Saharan Africa [49,51,94,114,115].

Some have, however, disputed the association of HIV prevalence and MC levels in such surveys. For example, Gisselquist et al refer to DHS data showing higher prevalence of HIV in circumcised men in seven of 13 sub-Saharan Africa countries [21]. In contrast, the ecological analysis of 118 developing countries by Drain and colleagues showed that high MC prevalence was strongly correlated with low HIV prevalence, independent of religion [94].

Furthermore, a recent cross-sectional analysis of DHS data for 18 countries across sub-Saharan Africa from 2003 to 2008 involving 70,554 males aged 15 to 59 years confirmed that being uncircumcised was significantly associated with risk of HIV infection (OR 4.12; 95% CI: 3.85-4.42) and that risk increases with number of lifetime partners [115]. In light of the probable conflict in interpretation, Wamai et al [116] have warned that DHS data must be used with caution because of their widely acknowledged inherent methodological problems, which Gersovitz asserts need to be overcome in order to improve reliability [117].

DHS data are, moreover, often bidirectional, indicating contrasting and context-specific effects. In Tanzania, for example, circumcision in men is higher in the upper quintiles of education and wealth, and such men have more sex partners [118]. So, not surprisingly, HIV prevalence in Tanzania, and numerous other countries across sub-Saharan Africa, is higher in people with higher education and income [119,120]. Furthermore, this relationship is not necessarily linear and can change over time [41]. The higher risky behaviour of such men, such as being more likely to have concurrent partners than uncircumcised men, would explain why, in certain settings, they have a high HIV prevalence despite being circumcised. This was pointed out in a recent analysis of surveys in 21 countries in sub-Saharan Africa [49].

Since DHS data involve self-reported surveys, multiple factors have to be considered when examining the relationship between MC and HIV prevalence. These include risky sexual behaviour, time of MC, whether circumcision was complete, partial or performed at all, marital status, education, wealth and patterns of residence (urban vs. rural). As an example, a study in Uganda by Gray et al of a large cohort of HIV-negative men found that MC significantly reduced HIV acquisition (unadjusted RR = 0.61; 95% CI = 0.37-0.97), but the protective effect was lower for post-pubertal circumcision (i.e., after 12 years of age); in Muslims, it was further confounded by cultural and behavioural factors [92]. In another example, a cross-sectional study in Kenya, Lesotho and Tanzania found that while the protective effect of MC in adolescents was only "probable", in adults, the association of MC with lower HIV infection was unequivocal, indicating a protective effect in males who were more likely to be sexually active [121].

There is a further point to note from ecological observation. Molecular clock analyses indicate that HIV has existed for about 70 years and may have originated in or near Cameroon (HIV-1), Guinea-Bissau (HIV-2) and the Congo [122,123]. Yet none of these countries, where most men are circumcised [69], have had adult prevalence rates as high as those observed in eastern and southern Africa [22,39]. Hence, it could be reasonably concluded that structural features of wealth and poverty patterning behaviour [41], reported practice of multiple and concurrent partnerships [49,52], couple discordancy [124], prevalence of other STIs [40,42,44] and geographic variations in MC [69,94] have synergized to provide the "perfect storm" for the HIV epidemic in sub-Saharan African countries with low MC prevalence [43,91].

Male circumcision for HIV prevention: saving lives and costs - the policy imperative

Unlike other HIV prevention strategies, MC is a one-time procedure conferring potentially lifelong protective benefits, so making it a highly cost-effective, life-saving intervention, as revealed by several studies subsequent to the RCTs [99,125-130]. For example, a study by the UNAIDS/WHO/SACEMA Expert Group on Modeling the Impact and Cost of Male Circumcision for HIV Prevention found that one HIV infection would be averted for every 15 circumcisions at a cost of US$150 to US$900 over a 10-year time horizon [130]. The population-level impact of MC in reducing HIV incidence at significant cost-savings is potentially enormous, as shown in an early modelling study [104].

The Male Circumcision: Decision Makers' Program Planning Tool (DMPPT), developed recently by USAID's Health Policy Initiative in collaboration with UNAIDS, has estimated the cost and impact of scaling up MC services [131]. Using this model, an analysis of 14 priority countries in eastern and southern Africa found that scaling up MC services to cover 80% of all adult men and newborn boys would, over the period 2009-2015, avert more than 4 million new adult HIV infections at a cost of US$2.5 billion [132]. This would yield total net saving on cost of antiretroviral therapy (ART) of US$20.2 billion over the same period [132].

In the DMPPT model, annual costs for implementation were projected to increase in the early scale-up phase due to increased demand, peaking in 2012 and declining thereafter, to level off at around $100 million by 2015. Even countries with moderate HIV prevalence, such as Rwanda, could reap significant savings in costs relative to lifetime HIV treatment [133]. Furthermore, the cost-effectiveness of MC, even in non- or low-generalized HIV settings, increases when the procedure is performed in newborns [134,135].

Despite being targeted at sexually active men, MC provides important direct and indirect benefits to women and children. For example, it was estimated that in high-prevalence areas in Kenya and Zimbabwe, "circumcision confers a 46% reduction in the rate of male-to-female HIV transmission", with the effect of the intervention "doubling the number of infections averted among women" [136]. On the other hand, a RCT in Uganda of sero-discordant couples in which the man was HIV-positive was discontinued for futility after 21.7% of women in the intervention group and 13.4% in the control group became infected [137]. This difference was not, however, statistically significant, and many men disobeyed instructions by resuming sexual intercourse before healing was complete [137]. More recent findings from a prospective multinational study in a similar sero-discordant population showed "no increased risk and potentially decreased risk" of infection due to MC to the female partners [138].

Since women in sub-Saharan Africa show high acceptability of MC as part of comprehensive strategies for HIV prevention, they can play an important role in the adoption and implementation of MC by changing male norms and in promoting infant MC [97,98,139]. By lowering infection in men and thence women, MC will reduce overall infection rate and lower the number of children being infected by their mother. Infant MC is, moreover, simpler, more convenient, entails lower risk and provides considerable savings in cost when compared with circumcision at a later age, including the cost of treatment over the lifetime for HIV-infected people [132-135,140,141]. As an example, one study in the USA indicated a 16% reduction in lifetime risk of HIV infection in all males when circumcision is done in infancy [134].

The cost savings from circumcision of boys early in life is considerably greater than this because they enter the sexually active period of their life with a reduced risk of various STIs [87,142-146]. In the Ugandan RCT of MC and HIV, MC was associated with a 25% reduction in prevalence in herpes simplex virus type 2 (HSV-2), 35% lower human papillomavirus (HPV) [147] and significantly reduced ulceration, trichomonas and bacterial vaginosis [148]. In the South African MC trial, low-risk HPV prevalence was 8.5% in the intervention arm compared with 15.8% in the control arm [149]. The strong protective mechanism by which MC prevents STIs in men likely involves both cellular and anatomical factors [105,147].

That MC affords protection against HIV and multiple STIs in heterosexual men and their female sexual partners, and thereby their children, is not in doubt. On the other hand, the effect of MC in preventing HIV in MSM is less certain. In a South African study, HIV in MSM was 80% lower if they were circumcised [150]. A meta-analysis of studies from countries worldwide showed 29% protection only for MSM who adopt primarily the insertive role [151]. This was 73% in a Cochrane analysis [152]. Not included was a recent study of MSM in the high-prevalence setting of Andhra Pradesh, India, where 18.6% of MSM were HIV positive [153]. Although HIV was 70% lower in circumcised receptive-only MSM, this was probably a result of homophily. Further research in sub-Saharan Africa that takes into account social and sexual networks in MSM is needed [152,153].

With the current strong evidence that MC protects against HIV and several common STIs, questions that are important for policy consideration have arisen. These include adverse effects, acceptability, risk compensation, reduced efficacy due to early return to sex after MC, disinhibition, long-term consequences and external validity, as well as ethical issues. These have been addressed in numerous publications [11,12,87,97,98,116,154-156], none of which regard these considerations as representing a basis for rejecting MC as part of HIV prevention strategies. For example, the arguments of external validity raised by Green et al [157] ignore long-standing evidence from observational studies [5] and have been strongly refuted as unfounded [158]. In other examples, studies on disinhibition [159] and risk compensation [155,160] showed no increase in risky sexual behaviour [160] or early resumption of sex [155].

Follow-up data of the Kenya RCT [2] indicated an ongoing increase in the protective effect of MC against HIV infections at 42 months [161] and 54 months [162]. By five years, the protective effect reached 73% in the Ugandan trial [163]. These results suggest that the positive effect of MC will continue [158]. However, implementation of national MC programmes triggered by the RCT findings did not begin until 2008 [7], starting in Kenya [164], and thus the long-term population impact remains to be observed in those particular areas. In light of that, it is imperative to continue monitoring sexual behaviour after circumcision for continued assessment of long-term positive impact.

Current state of practice in MC interventions in sub-Saharan Africa

Following the recommendation by global health agencies that MC be adopted as one of the critical tools for HIV prevention in high-prevalence generalized heterosexual epidemics [11,12], WHO and UNAIDS developed operational guidelines for scaling up MC services [165]. Programmatic development has, however, been slow, in large part as a consequence of suboptimal funding.

In 2008, researchers argued that the international community was not committing enough resources to MC commensurate with the available evidence on what works [166]. These authors noted that the 5% allocated for MC, from an overall budget of $3.2 billion that UNAIDS had estimated was needed to achieve universal coverage for HIV programmes by 2010, fell far short of the estimated need and demand for MC, especially given its demonstrated efficacy relative to other interventions. Table 2 summarizes the current state of MC intervention policy strategies, projected cost savings and infections averted, as well as MC provision to date in the 14 priority African countries. It can be seen that programmatic development of MC to date is ongoing in all countries, but differs markedly in extent [13,101,167].

Table 2. Design and implementation of MC services for HIV prevention in 14 priority countries in east and southern Africa, 2011

Implementation in Kenya, the first country to commence, was spearheaded by a national task force on MC in 2008 [14]. Other countries have, or are in the process of developing similar policies, implementation guidelines and strategies. Some, like Kenya and Lesotho, have developed formal MC policies, while others, such as Botswana and Rwanda, have incorporated MC into existing HIV prevention policies. Translating science into policy is often challenging [168], and we acknowledge that development of documents and programmes through consultative and collaborative processes involving stakeholders in the health ministries, HIV/AIDS agencies, non-governmental organizations, academia and donor partners, as was the case in Kenya, can be time consuming.

It is nevertheless of concern that the numbers circumcised across the various countries three years after policy recommendations are very low relative to targets (Table 2). The latest WHO/UNAIDS report indicates cumulative circumcision figures up to 2010 since scale-up started in 2008 at 555,202, i.e., 2.7% of the 20.8 million target [167]. That 74% (410,904) of these occurred in 2010 alone indicates that the momentum is rising, but needs to accelerate still. As the DMPPT modelling indicates, to achieve the projected outcomes, the 14 countries will need to reach 12 million circumcisions at peak period in 2012 [132]. Accordingly, five countries (Malawi, South Africa, Tanzania, Uganda and Zimbabwe) would require at least one million circumcisions each in 2012 [132].

In most of these countries, MC prevalence varies by region and it is logical that, in the scale-up phase, programmes for MC deliberately target low MC localities, such as is occurring in Ethiopia, Kenya and Namibia. However, many of the current programmes are confined to small or pilot settings. Data available for Lesotho are pre-scale up [169]; for Zimbabwe, they are from several clinical sites [167,170]; and for South Africa, they have scaled-up from Orange Farm [171], where the RCT in that country was conducted, to over 140 sites [167]. In Gambella, Ethiopia, services are currently provided in one hospital and seven health centres (personal communication, Hannah Gibson, Country Director Jhpiego, Ethiopia).

With a growing demand for MC services and the potential cost and life savings, it is imperative that scale up be rapidly accelerated [103]. At the current rate of service provision, 12 million MCs by 2012 across the 14 countries are highly unlikely to be met, so putting in jeopardy many lives and failing to achieve the desired cost savings.

In Kenya, just 232,200 MCs have been completed [167], the largest number of any country. A speeded-up rapid-results initiative intervention during a 30-day period in 2009 conducted by 95 teams, each of four persons, at a range of 9.6-22.8 circumcisions per team per day, achieved 36,000 circumcisions (Robert Bailey, personal communication). A similar intervention conducted over five weeks during November-December 2010 achieved 51,000 circumcisions (Robert Bailey, personal communication). At these rates, Kenya would need several similar rapid-results initiatives to reach the national goal of one million circumcisions by 2013 [172]. Nevertheless, Kenya's programme is a model for other African countries and, if adopted, could advance the 2012 goal.

Many challenges stand in the way of implementing MC programmes. These include cost, need for training of health personnel, other health system barriers, the politics surrounding policy development, funding and changing socio-cultural perceptions and beliefs about MC [13,94,101,164,166,172,173]. In Gambella, Ethiopia, the regional hospital reportedly cannot meet even a small demand of 10 circumcisions per week due to staff shortages and lack of training [173].

Currently, the most informative assessment of MC programmes comes from Kenya [164]. This report reveals that of 81 government health facilities surveyed in Nyanza (the target location of MC services), none had the capacity to implement the full package of voluntary circumcision outlined in the national guidelines [14]. Challenges included lack of a theatre, MC kits and supplies, medical personnel to perform the procedure, and data monitoring tools. Due to this, most of the reported 230,000 circumcisions were done by partner organizations largely in high-demand settings using mobile teams [164]. The Kenya programme offers many lessons for other countries.

Health provider training and service models being developed will need to be tailored around specific existing health systems and services infrastructure, HIV epidemiological profiles and determinants, as well as MC prevalence and demand. Reaching the estimated 100,000 men that need to be circumcised in Gambella, Ethiopia, for example, will require a massive increase in trained personnel to conduct the surgical procedure [173]. Since MC programmes are targeting healthy men, high standards for surgical staff training and post-operative care are essential. This includes strictly following established national and international guidelines for sterile surgical practice [11,12,14,144,165].

To increase the number of health personnel who can perform safe circumcisions, novel service models should be adopted. The rapid-results initiative pursued in Kenya is based on intensive mobilization of resources (human, equipment and financial) in high-demand settings through community approaches [164]. Models for Optimizing the Volume and Efficiency of MC Services ("MOVE") is an additional approach for meeting demand. Currently practiced in South Africa, it is focused on increasing the efficiency of staff and time by considering alternate surgical methods and modifying facilities for efficient use [174]. Consideration should also be given to promoting task shifting for nurses and clinical officers as per WHO guidelines [175]. Already in practice in Kenya [164] and Zambia [167], it is a component of proposals in several other countries, such as Namibia, Lesotho [13].

In some of the scale-up countries, traditional circumcisers, already used widely [72], can play a role in meeting demand [176], but only if they receive adequate certification for acceptable standards of surgical MC. On the other hand, as exemplified by the high (90%) preference among men and women for medical MC in a traditionally circumcising community from northern Tanzania, more efforts should be made to provide this medical service in a culturally appropriate fashion, so encouraging uptake [177].

Preliminary data are also becoming available on devices that could facilitate quicker and safer adult circumcision [178]. These include the Shang Ring [179] (which produced good results for safety and acceptability in a field test in Kenya [180]), circumcision template [181], the recently acclaimed PrePex system [182], and the Tara KLamp [183], for which further assessment is needed [178] after adverse effects were initially reported [184]. In an important development, WHO has provided a framework for clinical evaluation of devices for adult MC [185], in addition to those already recommended for infant MC [144].

Where do we go from here?

While welcoming continued debate about what drives HIV in high-prevalence populations and what works in HIV prevention programmes, we echo the call made by experts and advocates four years ago [186] and more recently [103], including a political declaration of the United Nations [187], urging an acceleration in implementation of proven approaches, such as MC. There are multiple reasons for reiterating this call. First, while the incidence of HIV is now declining in many countries in sub-Saharan Africa, nearly 70% of new HIV infections globally remain in this region [22]. The rate of new infections therefore needs to decelerate much faster there if the crisis is to be stemmed. Towards that end, policy makers, researchers and practitioners should direct energy towards viable, practical and efficacious solutions in an accelerated campaign.

Second, MC could stem epidemics of HIV elsewhere than Africa. Based on current UNAIDS data, the main mode of infection globally (heterosexual transmission) is growing, as reflected in the increasing proportion of new HIV infections reported in women, for example, to 35% in 2009 from 21% in 1990 in Asia [22]. Although in the USA, UK, Russia, Canada, Australia and the Asian region, major exposure categories are MSM and injecting drug users, higher incident HIV trends in women and heterosexual contacts [22,188] should ring alarm bells [143,156,189]. Such recent trends are likely to be exacerbated by uneven and declining MC levels, especially in such countries as the USA and Australia, which traditionally, until the mid-1970s and early 1980s, had MC rates of more than 90% [190,191]. In Australia, it is heartening that infant MC is again rising [156].

In such settings as the USA, MC services are particularly crucial, especially in African-Americans [189], who comprise a disproportionately high number of persons living with HIV [192,193] and in whom perinatal infection per 100,000 infants is 12.3 compared with just 0.5 in white infants [194]. Furthermore, African-Americans have the highest heterosexual HIV rates [195], but national data show that they also have rates of MC lower than whites [190]. Therefore, given the current epidemiological trends, interventions need to focus on established patterns of transmission for which the population-level impact in reducing HIV infections will be high now and in the future.

Third, current evidence from RCTs shows that in comparison to a protective effect of 46% for prophylaxis [196], 39% for microbicides [197] and 31.2% for a vaccine [198], at the moment, MC, with a 60% or higher efficacy [4], is the most effective biomedical HIV prevention strategy in heterosexual men. Furthermore, MC will help reduce HIV in women [136] and children [140,141,143], as well as help lower risks for STIs [146-148] that exacerbate HIV risk [199,200].

As part of the internationally recognized priority interventions for stemming HIV [201], and given the current state of implementation, massive catch-up strategies for adult MC seem to be the better investment in the short term. Importantly, mainstreaming of neonatal MC as part of a long-term strategy is both logical and clearly more cost effective [133,134,140,143,156], and will help systematize MC practice and services provision in the primary healthcare system for future generations. Furthermore, the much-needed scale up in sub-Saharan Africa will require significant additional funds, reorientation of expenditure allocation, and better, more rational use of the already existing largesse [132,164,166].

Last, continued research that addresses other issues concerning MC will be valuable, in addition to those already underway in various countries [13]. In particular, careful research is needed to:

1. Regularly update the impact of MC on the HIV epidemic in the targeted areas by monitoring behavioural changes following MC.

2. Compare different surgical approaches, including the use of different low-risk devices for adult MC to further improve on this procedure, and the cost effectiveness of service models, such as the rapid-results initiative, task shifting and "MOVE" for accelerating delivery.

3. Explore novel hypotheses relevant to prevention messaging, for example, does MC make condom use easier and/or more pleasurable?

4. Evaluate how to best integrate MC messages into existing communications and prevention programmes.

5. Develop strategies to improve the safety of traditional MC practices and norms so that these can be incorporated into regular scale-up programmes without increasing overall risk in order to speed up MC programmes.

6. Examine the effect of MC scale up on the health services and health system resources (human and infrastructural), as well as integration of the practice in the formal healthcare system.

7. Establish the definitive biologic mechanism by which MC protects against HIV infection through the penis.

8. Assess the role of MC as a potential platform for promoting men's health, including participation by women in order to encourage couple sexual and reproductive health.

9. Evaluate the integration of routine newborn MC in maternal-child health programmes.

Conclusions

Public health campaigns aimed at stemming the spread of HIV/AIDS should address all known transmission routes as specific epidemiological, resources and contextual factors demand. We support the continued promotion of the use of all effective methods. The effect of doing so will be cumulative. We realize that MC definitively disrupts the major mode of HIV transmission in sub-Saharan Africa. We also realize that historical, cultural and political controversies surrounding MC [86,88] may provoke passionate debates. However, as Collins argues, it is imperative that values underpinning scientific thought form the centre of public policy interventions [17].

Given the present body of evidence, and contingent on certain pre-conditions (e.g., that MC is conducted by a qualified practitioner, under acceptable conditions of hygiene, in the absence of contra-indications), at this point in time, it is clear that medical MC in infancy, childhood or adulthood produces far greater good than harm. We urge policy makers to more urgently facilitate implementation of MC as a public health measure to stem the growing heterosexual transmission of HIV worldwide and, in sub-Saharan Africa, to more quickly reduce future epidemics. Not only is MC highly efficacious against HIV acquisition, but it also confers multiple other health benefits, thus making it quite rightly a "surgical vaccine" for the 21st century [1,87,103,116,154].

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

RGW and BJM conceptualized the manuscript. RGW drafted and developed the manuscript. BJM did extensive reviews of subsequent drafts. RA was involved in editing and formatting the manuscript in various stages. SAB, DS, JDK, NS, DAC, JB, GB and ADW were involved in the early iteration of the manuscript and reviewed and made substantive contributions to the drafts. DS provided crucial data on male circumcision implementation. JBE read and provided insightful comments in the final revisions. All authors have contributed substantively in critically revising the content of the manuscript. All authors have read and approved the manuscript.

References

  1. Auvert B, Taljaard D, Lagarde E, Sobngwi-Tambekou J, Sitta R, Puren A: Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: The ANRS 1265 Trial.

    PLoS Med 2005, 2:1112-1122. OpenURL

  2. Bailey RC, Moses S, Parker CB, Agot K, Maclean I, Krieger JN, Williams CF, Campbell RT, Ndinya-Achola JO: Male circumcision for HIV prevention in young men in Kisumu, Kenya: A randomised controlled trial.

    Lancet 2007, 369:643-646. PubMed Abstract | Publisher Full Text OpenURL

  3. Gray RH, Kigozi G, Serwadda D, Makumbi F, Watya S, Nalugoda F, Kiwanuka N, Moulton LH, Chaudhary MA, Chen MZ, Sewankambo NK, Wabwire-Mangen F, Bacon MC, Williams CF, Opendi P, Reynolds SJ, Laeyendecker O, Quinn TC, Wawer MJ: Male circumcision for HIV prevention in men in Rakai, Uganda: A randomised trial.

    Lancet 2007, 369:657-666. PubMed Abstract | Publisher Full Text OpenURL

  4. Siegfried N, Muller M, Volmink J, Deeks JJ, Egger M, Low N, Weiss H, Walker S, Williamson P: Male circumcision for prevention of heterosexual acquisition of HIV in men (Review).

    Cochrane Database of Syst Rev 2009, 2:CD003362. OpenURL

  5. Lie RK, Miller FG: What counts as reliable evidence for public health policy: the case of circumcision for preventing HIV infection.

    BMC Med Res Methodol 2011, 11:34. PubMed Abstract | BioMed Central Full Text | PubMed Central Full Text OpenURL

  6. Weiss HA, Halperin D, Bailey RC, Hayes RJ, Schmid G, Hankins CA: Male circumcision for HIV prevention: from evidence to action?

    AIDS 2008, 22:567-574. PubMed Abstract | Publisher Full Text OpenURL

  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, 14:2361-2370. PubMed Abstract | Publisher Full Text OpenURL

  8. Mills E, Cooper C, Anema A, Guyatt A: Male circumcision for the prevention of heterosexually acquired HIV infection: a meta-analysis of randomized trials involving 11,050 men.

    HIV Med 2008, 9:332-335. PubMed Abstract | Publisher Full Text OpenURL

  9. Byakika-Tusiime J: Circumcision and HIV infection: assessment of causality.

    AIDS Behav 2008, 12:835-841. PubMed Abstract | Publisher Full Text OpenURL

  10. Hill BA: The environment and disease: Association or causation?

    Proc Royal Soc Med 1965, 58:295-300. OpenURL

  11. UNAIDS: [http://data.unaids.org/pub/Report/2008/JC1552_Circumcision_en.pdf] webcite

    Safe, Voluntary, Informed Male Circumcision and Comprehensive HIV Prevention Programming Guidance for decision-makers on human rights, ethical and legal considerations. OpenURL

  12. WHO/UNAIDS: [http://data.unaids.org/pub/Report/2007/mc_recommendations_en.pdf] webcite

    New Data on Male Circumcision and HIV Prevention: Policy and Program Implications. OpenURL

  13. WHO/UNAIDS: [http://www.who.int/hiv/pub/malecircumcision/MC_country_progress_June2010.pdf] webcite

    Progress in male circumcision scale-up: country implementation and research update. OpenURL

  14. Ministry of Health, National AIDS and STD Control Program: National Guidance for Voluntary Male Circumcision in Kenya. Nairobi; 2008. OpenURL

  15. Centers for Disease Control and Prevention: [http://www.cdc.gov/hiv/resources/qa/transmission.htm] webcite

    HIV Transmission. OpenURL

  16. Rotheram-Borus MJ, Swendeman D, Chovnick G: The past, present, and future of HIV prevention: integrating behavioral, biomedical, and structural intervention strategies for the next generation of HIV prevention.

    Annu Rev Clin Psychol 2009, 5:143-167. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  17. Collins H: We cannot live by skepticism alone.

    Nature 2009, 458:30-31. PubMed Abstract | Publisher Full Text OpenURL

  18. Global HIV Prevention Working Group: [http:/ / www.malecircumcision.org/ advocacy/ documents/ PWG_HIV_prevention_report_web.pdf] webcite

    Bringing HIV prevention to scale: an urgent global priority. OpenURL

  19. UNAIDS: [http:/ / www.unaids.org/ en/ media/ unaids/ contentassets/ dataimport/ publications/ irc-pub06/ jc1165-intensif_hiv-newstyle_en.pdf] webcite

    Intensifying HIV prevention: a UNAIDS policy position paper. OpenURL

  20. Chigwedere P, Seage GR, Gruskin S, Lee TH, Essex M: Estimating the lost benefits of antiretroviral drug use in South Africa.

    J Acquir Immune Defic Syndr 2008, 49(4):410-415. PubMed Abstract | Publisher Full Text OpenURL

  21. Gisselquist D, Potterat JJ, St Lawrence JS, Hogan M, Arora NK, Correa M, Dinsmore WW, Mehta G, Millogo J, Muth SQ, Okinyi M, Ounga T: How to contain generalized HIV epidemics? A plea for better evidence to displace speculation.

    Int J STD AIDS 2009, 20:443-446. PubMed Abstract | Publisher Full Text OpenURL

  22. UNAIDS: [http:/ / www.unaids.org/ en/ media/ unaids/ contentassets/ documents/ unaidspublication/ 2010/ 20101123_globalreport_en[1].pdf] webcite

    Report on the Global AIDS Epidemic. OpenURL

  23. Wellings K, Collumbien M, Slaymaker E, Singh S, Hodges Z, Patel D, Bajos N: Sexual behavior in context: A global perspective.

    Lancet 2006, 368:1706-1728. PubMed Abstract | Publisher Full Text OpenURL

  24. Baggaley RF, Fraser C: Modelling sexual transmission of HIV: testing the assumptions, validating the predictions.

    Curr Opin HIV AIDS 2010, 5:269-276. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  25. Hethcote HW, Van Ark JW: [http://biotech.law.lsu.edu/cphl/Models/aids/] webcite

    Modeling HIV transistor and AIDS in the United States. OpenURL

  26. Miller WC: Role of acute and early HIV infection in the sexual transmission of HIV.

    Current Opinion in HIV & AIDS 2010, 5:277-282. PubMed Abstract | Publisher Full Text OpenURL

  27. Robinson NJ, Mulder DW, Auvert B, Hayes RJ: Modelling the impact of alternative HIV intervention strategies in rural Uganda.

    AIDS 1995, 9:1263-1270. PubMed Abstract | Publisher Full Text OpenURL

  28. Leclerc PM, Matthews AP, Garenne ML: Fitting the HIV epidemic in Zambia: a two-sex micro-simulation model.

    PLoS One 2009, 4:e5439. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  29. UNAIDS: [http:/ / www.unaids.org/ en/ dataanalysis/ monitoringcountryprogress/ 2010progressreportssubmittedbycount ries/ ] webcite

    2010 progress reports submitted by countries. OpenURL

  30. WHO/UNAIDS: [http://www.who.int/hiv/pub/surveillance/en/cds_edc_2000_5.pdf] webcite

    Guidelines for second generation HIV surveillance: the next decade. OpenURL

  31. Centers for Disease Control and Prevention: Guidelines for National Human Immunodeficiency Virus Case Surveillance, Including Monitoring for Human Immunodeficiency Virus Infection and Acquired Immunodeficiency Syndrome. [http://www.cdc.gov/mmwr/preview/mmwrhtml/rr4813a1.htm] webcite

    MMWR 1999, 48(RR13):1-28. PubMed Abstract OpenURL

  32. Brown T, Bao L, Raftery AE, Solomon JA, Baggaley RF, Stover J, Gerland P: Modelling HIV epidemics in the antiretroviral era: the UNAIDS Estimation and Projection package 2009.

    STI Supplement 2010, 86(Suppl 2):ii3e10. OpenURL

  33. Stover J, Johnson P, Hallett T, Marston M, Becquet R, Timaeus IM: The Spectrum projection package: improvements in estimating incidence by age and sex, mother-to-child transmission, HIV progression in children and double orphans.

    Sex Transm Infect 2010, 86(Suppl 2):ii16e21. OpenURL

  34. Ghys P, Garnett GP: The 2009 HIV and AIDS estimates and projections: methods, tools and analyses.

    Sex Transm Infect 2010, 86:ii1-ii2. Publisher Full Text OpenURL

  35. UNAIDS Reference Group on Estimates, Modeling and Projections [http://www.epidem.org/] webcite

  36. Varghese B, Maher JE, Peterman TA, Branson BM, Stekette RW: Reducing the risk of sexual HIV transmission: quantifying the per-act risk for HIV on the basis of choice of partner, sex act, and condom use.

    Sex Transm Dis 2002, 29:38-43. PubMed Abstract | Publisher Full Text OpenURL

  37. Boily M-C, Baggaley RF, Wang L, Masse B, White RG, Hayes RJ, Alary M: Heterosexual risk of HIV-1 infection per sexual act: systematic review and meta-analysis of observational studies.

    Lancet Infect Dis 2009, 9:118-129. PubMed Abstract | Publisher Full Text OpenURL

  38. Orroth KK, White RG, Freeman EE, Bakker R, Buvé A, Glynn JR, Dik F Habbema J, Hayes RJ: Attempting to explain heterogeneous HIV epidemics in sub-Saharan Africa: potential role of.

    Sex Transm Infect 2011, in press. OpenURL

  39. Denis P, Becker C: The HIV/AIDS epidemic in sub-Saharan Africa in a historical perspective. [http://rds.refer.sn/IMG/pdf/AIDSHISTORYALL.pdf] webcite

    Senegalese Network "Law, Ethics, Health" 2006. PubMed Abstract | Publisher Full Text OpenURL

  40. Sousa JD, Muller V, Lemey P, Vandamme AM: High GUD incidence in the early 20th century created a particularly permissive time window for the origin and initial spread of epidemic HIV strains.

    PLoS ONE 2010, 5:e9936. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  41. Parkhurst JO: Understanding the correlations between wealth, poverty and human immunodeficiency virus infection in African countries.

    Bull World Health Organ 2010, 88:481-560. OpenURL

  42. Auvert B, Buvé A, Ferry B, Caraël M, Morison L, Lagarde E, Robinson NJ, Kahindo M, Chege J, Rutenberg N, Musonda R, Laourou M, Akam E, Study Group on the Heterogeneity of HIV Epidemics in African Cities: Ecological and individual level analysis of risk factors for HIV infection in four urban populations in sub-Saharan Africa with different levels of HIV infection.

    AIDS 2001, 15(Suppl):S15-S30. PubMed Abstract | Publisher Full Text OpenURL

  43. Buve A: The HIV epidemics in sub-Saharan Africa: why so severe? Why so heterogenous? An epidemiological perspective. In The HIV/AIDS Epidemic in Sub-Saharan Africa in a Historical Perspective. Edited by Denis P, Becker C. Senegalese Network "Law, Ethics, Health"; 2006:41-55. OpenURL

  44. Sobngwi-Tambekou J, Taljaard D, Lissouba P, Zarca K, Puren A, Lagarde E, Auvert B: Effect of HSV-2 serostatus on acquisition of HIV by young men: results of a longitudinal study in Orange Farm, South Africa.

    J Infect Dis 2009, 199:958-964. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  45. Buvé A, Caraël M, Hayes RJ, Auvert B, Ferry B, Robinson NJ, Anagonou S, Kanhonou L, Laourou M, Abega S, Akam E, Zekeng L, Chege J, Kahindo M, Rutenberg N, Kaona F, Musonda R, Sukwa T, Morison L, Weiss HA, Laga M, Study Group on Heterogeneity of HIV Epidemics in African Cities: Multicentre study on factors determining differences in rate of spread of HIV in sub-Saharan Africa: methods and prevalence of HIV infection.

    AIDS 2001, 15(Suppl 4):S5-S14. PubMed Abstract | Publisher Full Text OpenURL

  46. Halperin D, Epstein H: Concurrent sexual partnerships help explain Africa's high HIV prevalence: implications for prevention.

    Lancet 2004, 364:4-6. PubMed Abstract | Publisher Full Text OpenURL

  47. Shelton JD: Why multiple sexual partners?

    Lancet 2009, 374-367. OpenURL

  48. Morris M: Barking up the wrong evidence tree. Comment on Lurie & Rosenthal, ''Concurrent partnerships as a driver of the HIV epidemic in Sub-Saharan Africa? The evidence is limited".

    AIDS Behav 2010, 14:31-33. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  49. Mishra V, Assche SBV: [http://www.measuredhs.com/pubs/pdf/WP62/WP62.pdf] webcite

    Concurrent sexual partnerships and HIV infection: Evidence from national population based surveys. 2009.

    DHS Working Paper 62;

    OpenURL

  50. Wellings K, Collumbien M, Slaymaker E, Singh S, Hodges Z, Patel D, Bajos N: Sexual behavior in context: A global perspective.

    Lancet 2006, 368:1706-1728. PubMed Abstract | Publisher Full Text OpenURL

  51. Reniers G, Tfaily R: Polygyny and HIV in Malawi.

    Demographic Resh 2008, 19:1811-1830. OpenURL

  52. One Love: [http:/ / www.onelovesouthernafrica.org/ wp-content/ uploads/ 2009/ 01/ mcp-reportwith-cover-final.pdf] webcite

    Multiple and concurrent sexual partnerships in Southern Africa: a ten country research report. OpenURL

  53. Watts CH, May RM: The influence of concurrent partnerships on the dynamics of HIV/AIDS.

    Mathematical Biosciences 1992, 108:89-104. PubMed Abstract | Publisher Full Text OpenURL

  54. Morris M, Kretzschmar M: Concurrent partnerships and transmission dynamics in networks.

    Social Networks 1995, 17:299-318. Publisher Full Text OpenURL

  55. Lurie MN, Rosenthal S: Concurrent partnerships as a driver of the HIV epidemic in sub-saharan Africa? The evidence is limited.

    AIDS Behav 2010, 14:17-24. PubMed Abstract | Publisher Full Text OpenURL

  56. Sawers L, Stillwaggon E: Concurrent sexual partnerships do not explain the HIV epidemics in Africa: a systematic review of the evidence.

    J Int AIDS Soc 2010, 13:34. PubMed Abstract | BioMed Central Full Text | PubMed Central Full Text OpenURL

  57. World Bank and USAID: Emerging Issues in today's HIV response. [http:/ / siteresources.worldbank.org/ INTHIVAIDS/ Resources/ 375798-1297872065987/ Debate4SUMMARYConcurrentSexualPartn erships.pdf] webcite

  58. Chin J, Sato PA, Mann JM: Projections of HIV infections and AIDS cases to the year 2000.

    Bull World Health Organ 1990, 68:1-11. PubMed Abstract | PubMed Central Full Text OpenURL

  59. Simonsen L, Kane A, Lloyd J, Zaffran M, Kane M: Unsafe injections in the developing world and transmission of bloodborne pathogens: a review.

    Bull World Health Organ 1999, 77:789-800. PubMed Abstract | PubMed Central Full Text OpenURL

  60. Mathers BM, Degenhardt L, Phillips B, Wiessing L, Hickman M, Strathdee SA, Wodak A, Panda S, Tyndall M, Toufik A, Mattick RP, 2007 Reference Group to the UN on HIV and Injecting Drug Use: Global epidemiology of injecting drug use and HIV among people who inject drugs: a systematic review.

    Lancet 2008, 372:1733-1745. PubMed Abstract | Publisher Full Text OpenURL

  61. Gouws E, White PJ, Stover J, Brown T: Short term estimates of adult HIV incidence by mode of transmission: Kenya and Thailand as examples.

    Sex Transm Infect 2006, 82(Suppl 3):iii51-iii55. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  62. Mishra V, Khan S, Liu L, Kottiri B: [http://www.measuredhs.com/pubs/pdf/CR21/CR21.pdf] webcite

    Medical Injection Use and HIV in Sub-Saharan Africa, DHS comparative studies no. 21. Calverton: Macro International; 2008. OpenURL

  63. World Health Organization: [http://www.who.int/hiv/pub/mtct/strategic_vision.pdf] webcite

    PMTCT strategic vision 2010-2015: preventing mother-to-child transmission of HIV to reach the UNGASS and Millennium Development Goals. OpenURL

  64. Mahy M, Kiragu K, Hayashi C, Akwara P, Luo C, Stanecki K, Ekpini R, Shaffer N: What will it take to achieve virtual elimination of mother-to-child transmission of HIV? An assessment of current progress and future needs.

    Sex Transm Infect 2010, 86:ii48-ii55. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  65. Smith AD, Tapsoba P, Peshu N, Sanders EJ, Jaffe HW: Men who have sex with men and HIV/AIDS in sub-Saharan Africa.

    Lancet 2009, 374:416-422. PubMed Abstract | Publisher Full Text OpenURL

  66. Baral S, Sifakis F, Cleghorn F, Beyrer C: Elevated risk for HIV infection among men who have sex with men in low- and middle-income countries 2000-2006: A systematic review.

    PLoS Med 2007, 4:e339. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  67. Hrdy DB: Cultural practices contributing to transmission of human immunodeficiency virus in Africa.

    Rev Infect Dis 1987, 9:1109-1119. PubMed Abstract | Publisher Full Text OpenURL

  68. Ounga T, Okinyi M, Onyuro S, Correa M, Gisselquist D: Exploratory study of blood exposures that are risks for HIV among Luo and Kisii ethnic groups in Nyanza province, Kenya.

    Int J STD AIDS 2009, 20:19-23. PubMed Abstract | Publisher Full Text OpenURL

  69. WHO/UNAIDS: [http://whqlibdoc.who.int/publications/2007/9789241596169_eng.pdf] webcite

    Male circumcision: Global trends and determinants of prevalence, safety and acceptability. OpenURL

  70. WHO: [http://libdoc.who.int/publications/2009/9789241598910_eng.pdf] webcite

    Traditional male circumcision among young people: a public health perspective in the context of HIV prevention. OpenURL

  71. Bailey RC, Egesah O, Rosenberg S: Male circumcision for HIV prevention: a prospective study of complications in clinical and traditional settings in Bungoma, Kenya.

    Bull World Health Organ 2008, 86:669-677. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  72. Wilcken A, Keil T, Dick B: Traditional male circumcision in eastern and southern Africa: a systematic review of prevalence and complications.

    Bull World Health Organ 2010, 88:907-914. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  73. Apetrei C, Becker J, Metzger M, Gautam R, Engle J, Wales AK, Eyong M, Enyong P, Sama M, Foley BT, Drucker E, Marx PA: Potential for HIV transmission through unsafe injections.

    AIDS 2006, 20:1074-1076. PubMed Abstract | Publisher Full Text OpenURL

  74. Reid SR: Injection drug use, unsafe medical injections, and HIV in Africa: a systematic review.

    Harm Reduct J 2009, 6:24. PubMed Abstract | BioMed Central Full Text | PubMed Central Full Text OpenURL

  75. Hiemstra R, Rabie H, Schaaf HS, Eley B, Cameron N, Mehtar S, Janse van Rensburg A, Cotton MF: Unexplained HIV-1 infection in children -- documenting cases and assessing for possible risk factors.

    S Afr Med J 2004, 94:188-193. PubMed Abstract | Publisher Full Text OpenURL

  76. Schmid GP, Buvé A, Mugyenyi P, Garnett GP, Hayes RJ, Williams BG, Calleja JG, De Cock KM, Whitworth JA, Kapiga SH, Ghys PD, Hankins C, Zaba B, Heimer R, Boerma JT: Transmission of HIV-1 infection in sub-Saharan Africa and effect of elimination of unsafe injections.

    Lancet 2004, 363:482-488. PubMed Abstract | Publisher Full Text OpenURL

  77. de Walque D: Do unsafe tetanus toxoid injections play a significant role in the transmission of HIV/AIDS? Evidence from seven African countries.

    Sex Transm Infect 2008, 84:122-125. PubMed Abstract | Publisher Full Text OpenURL

  78. Khobotlo M, Tshehlo R, Nkonyana J, Ramoseme M, Khobotle M, Chitoshia A, Hildebrand M, Fraser N: Lesotho: HIV prevention response and modes of transmission analysis. Maseru: Lesotho National AIDS Commission; 2009.

  79. Mngadi S, Fraser N, Mkhatshwa H, Lapidos P, Khumalo T, Tsela S, Nhlabatsi N, Odido H: Swaziland: HIV prevention response and modes of transmission analysis. Mbabane, National Emergency Response Council on HIV/AIDS; 2009. OpenURL

  80. Wabwire-Mangen F, Odiit M, Kirungi W, Kisitu DK, Wanyama JO: Uganda: HIV modes of transmission and prevention response analysis. Kampala: Uganda National AIDS Commission; 2009. OpenURL

  81. Mulenga O, Witola H, Buyu C, Gboun M, Sunkutu MR, Rodriguez-Garcia R, Gorgens M, Fraser-Hurt N, Sattin E, Potter D, Dzekedzeke K, Banda R, Michelo C: Zambia: HIV prevention response and modes of transmission analysis. Lusaka: Zambia National HIV/AIDS/STI/TB Council;; 2009. OpenURL

  82. Baral S, Dausab F, Masenior N, Iipinge S, Beyrer C: A Systematic Review of HIV epidemiology and risk factors among MSM in Sub-Saharan Africa 2000-2008. XVII International AIDS Conference, Mexico City; 2008.

    Abstract #MOPE0393

  83. Sanders EJ, Graham SM, Okuku HS, van der Elst EM, Muhaari A, Davies A, Peshu N, Price M, McClelland : HIV-1 infection in high risk men who have sex with men in Mombasa, Kenya.

    AIDS 2007, 21:2513-2520. PubMed Abstract | Publisher Full Text OpenURL

  84. Brody S, Potterat JJ: Establishing valid AIDS monitoring and research in countries with generalized epidemics.

    Int J STD AIDS 2004, 15:1-6. PubMed Abstract | Publisher Full Text OpenURL

  85. Lagarde E, Caraël M, Auvert B, Buve A: Concurrency and sexual transmission: a response to the letter by Rothenberg et al.

    AIDS 2002, 16:679-680. Publisher Full Text OpenURL

  86. Kaicher DC, Swan KG: A Cut Above: Circumcision as an ancient status symbol.

    Urology 2010, 76:18-20. PubMed Abstract | Publisher Full Text OpenURL

  87. Morris BJ: Why circumcision is a biomedical imperative for the 21st century.

    BioEssays 2007, 29:1147-1158. PubMed Abstract | Publisher Full Text OpenURL

  88. Gollaher D: A History of the World's Most Controversial Surgery. New York; 2000. PubMed Abstract | Publisher Full Text OpenURL

  89. Alcena V: AIDS in third world countries.

    New York State J Med 1986, 86:446. OpenURL

  90. Fink AJ: A possible explanation for heterosexual male infection with AIDS.

    N Engl J Med 1986, 315:1167. PubMed Abstract OpenURL

  91. Bongaarts J, Reining P, Way P, Conant F: The relationship between male circumcision and HIV infection in African populations.

    AIDS 1989, 3:373-377. PubMed Abstract | Publisher Full Text OpenURL

  92. Gray RH, Kiwanuka N, Quinn TC, Sewankambo NK, Serwadda D, Mangen FW, Lutalo T, Nalugoda F, Kelly R, Meehan M, Chen MZ, Li C, Wawer MJ: Male circumcision and HIV acquisition and transmission: cohort studies in Rakai, Uganda.

    AIDS 2000, 14:2371-2381. PubMed Abstract | Publisher Full Text OpenURL

  93. Siegfried N, Muller M, Deeks J, Volmink J, Egger M, Low N, Walker S, Williamson P: HIV and male circumcision - a systematic review with assessment of the quality of studies.

    Lancet Infect Dis 2005, 5:165-173. PubMed Abstract | Publisher Full Text OpenURL

  94. Drain PK, Halperin DT, Hughes JP, Klausner JD, Bailey RC: Male circumcision, religion and infectious diseases: An ecologic analysis of 118 developing countries.

    BMC Infect Dis 2006, 6:172. PubMed Abstract | BioMed Central Full Text | PubMed Central Full Text OpenURL

  95. Padian NS, McCoy SI, Balkus JE, Wasserheit JN: Weighing the gold in the gold standard: challenges in HIV prevention research.

    AIDS 2010, 24:621-635. PubMed Abstract | Publisher Full Text OpenURL

  96. [http://www.malecircumcision.org/index.html] webcite

    Clearing House on Male Circumcision for HIV Prevention. OpenURL

  97. Westercamp N, Bailey RC: Acceptability of Male Circumcision for Prevention of HIV/AIDS in Sub-Saharan Africa: A Review.

    AIDS Behav 2007, 11:341-355. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  98. Bailey RC: Acceptability of male circumcision for prevention of HIV infection in Zambia.

    AIDS Care 2007, 19:471-477. PubMed Abstract | Publisher Full Text OpenURL

  99. Williams BG, Lloyd-Smith JO, Gouws E, Hankins C, Getz WM, Hargrove J, de Zoysa I, Dye C, Auvert B: The potential impact of male circumcision on HIV in sub-Saharan Africa.

    PLoS Med 2006, 3:e262. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  100. Sawires SR, Dworkin SL Fiamma A, Peacock D, Szekeres G, Coates TJ: Male circumcision and HIV/AIDS: challenges and opportunities.

    Lancet 2007, 369:708-713. PubMed Abstract | Publisher Full Text OpenURL

  101. De Bruyn G, Martinson N, Gray GE: Male circumcision for HIV prevention: developments from sub-Saharan Africa.

    Expert Rev Anti Infect Ther 2010, 8:23-31. PubMed Abstract | Publisher Full Text OpenURL

  102. Doyle SM, Khan JG, Hosang N, Carroll PR: The impact of male circumcision on HIV transmission.

    J Urol 2010, 182:21-26. OpenURL

  103. Center for Global Health Policy: [http:/ / www.idsaglobalhealth.org/ uploadedFiles/ GlobalHealth/ MC%20Issue%20Brief.pdf] webcite

    Medical Male Circumcision as HIV Prevention: Follow the Evidence: The case for aggressive scale up. OpenURL

  104. Nagelkerke NJ, Moses S, de Vlas SJ, Bailey RC: Modelling the public health impact of male circumcision for HIV prevention in high prevalence areas in Africa.

    BMC Infect Dis 2007, 7:16. PubMed Abstract | BioMed Central Full Text | PubMed Central Full Text OpenURL

  105. Szabo R, Short RV: How does male circumcision protect against HIV infection?

    BMJ 2000, 320:1592. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  106. Patterson BK, Landay A, Siegel JN, Flener Z, Pessis D, Chaviano A, Bailey RC: Susceptibility to human immunodeficiency virus-1 infection of human foreskin and cervical tissue grown in explant culture.

    Am J Pathol 2002, 161:867-873. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  107. de Witte L, Nabatov A, Pion M, Fluitsma D, de Jong MAWP, de Gruijl T, Piguet V, van Kooyk Y, Geijtenbeek1 TBH: Langerin is a natural barrier to HIV-1 transmission by Langerhans cells.

    Nat Med 2007, 13:367-371. PubMed Abstract | Publisher Full Text OpenURL

  108. Ganor Y, Zhou Z, Tudor D, Schmitt A, Vacher-Lavenu MC, Gibault L, Thiounn N, Tomasini J, Wolf JP, Bomsel M: Within 1 h, HIV-1 uses viral synapses to enter efficiently the inner, but not outer, foreskin mucosa and engages Langerhans-T cell conjugates.

    Mucosal Immunol 2010, 3:506-522. PubMed Abstract | Publisher Full Text OpenURL

  109. Ganor Y, Bomsel M: HIV-1 Transmission in the male genital tract.

    Am J Reprod Immunol 2011, 65:284-291. PubMed Abstract | Publisher Full Text OpenURL

  110. Dinh MH, McRaven MD, Kelley ZL, Penugonda S, Hope TJ: Keratinization of the adult male foreskin and implications for male circumcision.

    AIDS 2010, 24:899-906. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  111. Qin Q, Zheng XY, Wang YY, Shen HF, Sun F, Ding W: Langerhans' cell density and degree of keratinization in foreskins of Chinese preschool boys and adults.

    Int Urol Nephrol 2009, 41:747-753. PubMed Abstract | Publisher Full Text OpenURL

  112. Fischetti L, Barry SM, Hope TJ, Shattock RJ: HIV-1 infection of human penile explant tissue and protection by candidate microbicides.

    AIDS 2009, 23:319-328. PubMed Abstract | Publisher Full Text OpenURL

  113. Dinh MH, Fahrbach KM, Hope TJ: The role of the foreskin in male circumcision: an evidence-based review.

    Am J Reprod Immunol 2010, 65:279-283. PubMed Abstract | Publisher Full Text OpenURL

  114. Ministry of Health, National AIDS and STI Control Program: Kenya AIDS Indicator Survey 2007. Nairobi; 2008. OpenURL

  115. Gebremedhin S: Assessment of the Protective Effect of Male Circumcision from HIV Infection and Sexually Transmitted Diseases: Evidence from 18 Demographic and Health Surveys in Sub-Saharan Africa.

    Afr J Reprod Health 2010, 14:105-113. PubMed Abstract OpenURL

  116. Wamai RG, Weiss HA, Hankins C, Karim QA, Shisana O, Bailey RC, Betukumesu B, Bongaarts J, Bowa K, Cash R, Cates W, Diallo MO, Dludlu S, Geffen N, Heywood M, Jackson H, Kayembe PK, Kapiga S, Kebaabetswe P, Kintaudi L, Klausner JD, Leclerc-Madlala S, Mabuza K, Benjamin Makhubele M, Micheni K, Morris BJ, de Moya A, Ncala J, Ntaganira I, Nyamucherera OF, Otolorin EO, Pape JW, Phiri M, Rees H, Ruiz M, Sanchez J, Sawires S, Seloilwe ES, Serwadda DM, Setswe G, Sewankambo N, Simelane D, Venter F, Wilson D, Woelk G, Zungu N, Halperin DT: Male circumcision is an efficacious, lasting and cost-effective strategy for combating HIV in high-prevalence AIDS epidemics: time to move beyond debating the science.

    Fut HIV Ther 2008, 2:399-405. Publisher Full Text OpenURL

  117. Gersovitz M: The HIV epidemic in four African countries seen through the demographic and health surveys.

    J Afr Econ 2005, 14:191-246. Publisher Full Text OpenURL

  118. Tanzania Commission for AIDS (TACAIDS), National Bureau of Statistics (NBS), ORC Macro: [http://www.tgpsh.or.tz/fileadmin/uploads/docs/THIS_FINAL_2005.pdf] webcite

    Tanzania HIV/AIDS Indicator Survey 2003-04. Calverton, Maryland, USA: TACAIDS, NBS, and ORC Macro; 2005. OpenURL

  119. Lowndes CM, Alary M, Belleau M, Bosu WK, Kintin DF, Nnorom JA, Seck K, Victor-Ahuchogu J, Wilson D: West Africa HIV/AIDS epidemiology and response synthesis: implications for prevention. Washington, DC: World Bank; 2008. OpenURL

  120. Piot P, Greener R, Russell S: Squaring the circle: AIDS, poverty, and human development.

    PLoS Med 2007, 4:e314. Publisher Full Text OpenURL

  121. Brewer DD, Potterat JJ, Roberts JM, Brody S: Male and female circumcision associated with prevalent HIV infection in virgins and adolescents in Kenya, Lesotho, and Tanzania.

    Ann Epidemiol 2007, 17:217-226. PubMed Abstract | Publisher Full Text OpenURL

  122. Keele BF, Van Heuverswyn F, Li Y, Bailes E, Takehisa J, Santiago ML, Bibollet-Ruche F, Chen Y, Wain LV, Liegeois F, Loul S, Ngole EM, Bienvenue Y, Delaporte E, Brookfield JFY, Sharp PM, Shaw GM, Peeters M, Hahn BH: Chimpanzee reservoirs of pandemic and nonpandemic HIV-1.

    Science 2006, 313:523-526. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  123. Lemey P, Pybus OG, Wang B, Saksena NK, Salemi M, Vandamme AM: Tracing the origin and history of the HIV-2 epidemic.

    Proc Natl Acad Sci USA 2003, 100:6588-6592. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  124. Eyawo O, de Walque D, Ford N, Gakii G, Lester RT, Mills EJ: HIV status in discordant couples in sub-Saharan Africa: a systematic review and meta-analysis.

    Lancet Infect Dis 2010, 10:770-777. PubMed Abstract | Publisher Full Text OpenURL

  125. Kahn JG, Marseille E, Auvert B: Cost-effectiveness of male circumcision for HIV prevention in a South African setting.

    PLoS Med 2006, 3:e517. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  126. Gray RH, Li X, Kigozi G, Serwadda D, Nalugoda F, Watya S, Reynolds SJ, Wawer M: The impact of male circumcision on HIV incidence and cost per infection prevented: a stochastic simulation model from Rakai, Uganda.

    AIDS 2007, 21:845-850. PubMed Abstract | Publisher Full Text OpenURL

  127. Londish GJ, Murray JM: Significant reduction in HIV prevalence according to male circumcision intervention in sub-Saharan Africa.

    Int J Epidemiol 2008, 37:1246-1253. PubMed Abstract | Publisher Full Text OpenURL

  128. Galarraga O, Colchero A, Wamai RG, Bertozzi SM: HIV Prevention Cost-Effectiveness: A Systematic Review.

    BMC Public Health 2009, 9(Suppl 1):S5. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  129. Uthman OA, Popoola TA, Uthman MMB, Olatunde A: Economic evaluations of adult male circumcision for prevention of heterosexual acquisition of HIV in men in sub-Saharan Africa: a systematic review.

    PLoS One 2010, 5:e9628. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  130. UNAIDS/WHO/SACEMA Expert Group on Modeling the Impact and Cost of Male Circumcision for HIV Prevention: Male circumcision for HIV prevention in high HIV prevalence settings: what can mathematical modeling contribute to informed decision making?

    PLoS Med 2009, 6:e1000109. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  131. Health Policy Initiative: [http:/ / www.healthpolicyinitiative.com/ index.cfm?id=software&get=MaleCircu mcision] webcite

    Male Circumcision Decisionmakers Tool. OpenURL

  132. USAID Health Policy Initiative: [http:/ / www.malecircumcision.org/ programs/ documents/ 14_country_summary11309.pdf] webcite

    The Potential Cost and Impact of Expanding Male Circumcision in 14 African Countries. OpenURL

  133. Binagwaho A, Pegurri E, Muita J, Bertozzi S: Male circumcision at different ages in Rwanda: a cost-effectiveness study.

    PLoS Med 2010, 7:e1000211. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  134. Sansom SL, Prabhu VS, Hutchinson AB, An Q, Hall HI, Shrestha RK, Lasry A, Taylor AW: Cost-effectiveness of newborn circumcision in reducing lifetime HIV risk among U.S. males.

    PLoS One 2010, 5:e8723. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  135. White RG, Glynn JR, Orroth KK, Freeman EE, Bakker R, Weiss HA, Kumaranayake L, Habbema JD, Buvé A, Hayes RJ: Male circumcision for HIV prevention in sub-Saharan Africa: who, what and when?

    AIDS 2008, 22:1841-1850. PubMed Abstract | Publisher Full Text OpenURL

  136. Hallett TB, Alsallaq RA, Baeten JM, Weiss H, Celum C, Gray R, Abu-Raddad L: Will circumcision provide even more protection from HIV to women and men? New estimates of the population impact of circumcision interventions.

    Sex Transm Infect 2011, 87:88-93. PubMed Abstract | Publisher Full Text OpenURL

  137. Wawer MJ, Makumbi F, Kigozi G, Serwadda D, Watya S, Nalugoda F, Buwembo D, Ssempijja V, Kiwanuka N, Moulton LH, Sewankambo NK, Reynolds SJ, Quinn TC, Opendi P, Iga B, Ridzon R, Laeyendecker O, Gray RH: Circumcision in HIV-infected men and its eff ect on HIV transmission to female partners in Rakai, Uganda: a randomised controlled trial.

    Lancet 2009, 374:229-237. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  138. Baeten JM, Donnell D, Kapiga SH, Ronald A, John-Stewart G, Inambao M, Manongi R, Vwalika B, Celum C, Partners in Prevention HSV/HIV Transmission Study Team: Male circumcision and risk of male-to-female HIV-1 transmission: a multinational prospective study in African HIV-1-serodiscordant couples.

    AIDS 2010, 24:737-744. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  139. Centre for HIV/AIDS Prevention Studies: Women and MMC: interview with Prof Bertran Auvert. Centre for HIV/AIDS Prevention Studies; 2011. OpenURL

  140. Schoen EJ, Oehrli M, Colby CJ, Machin G: The highly protective effect of newborn circumcision against invasive penile cancer.

    Pediatrics 2000, 105:e36. PubMed Abstract | Publisher Full Text OpenURL

  141. UNAIDS: [http:/ / www.malecircumcision.org/ research/ documents/ Neonatal_child_MC_global_review.pdf] webcite

    Neonatal and child male circumcision: a global review. OpenURL

  142. Weiss GN: Prophylactic neonatal surgery and infectious diseases.

    Pediat Infect Dis J 1997, 16:727-734. Publisher Full Text OpenURL

  143. Tobian AA, Gray RH, Quinn TC: Male circumcision for the prevention of acquisition and transmission of sexually transmitted infections: the case for neonatal circumcision.

    Arch Pediatr Adolesc Med 2010, 164:78-84. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  144. WHO and Jhpiego: [http://whqlibdoc.who.int/publications/2010/9789241500753_eng.pdf] webcite

    Manual for early infant male circumcision under local anaesthesia. OpenURL

  145. MacNeily AE, Afshar K: Circumcision and non-HIV sexually transmitted infections.

    Can Urol Assoc J 2011, 5:58-59. PubMed Abstract | PubMed Central Full Text OpenURL

  146. Morris BJ, Gray RH, Castellsague X, Bosch FX, Halperin DT, Waskett JH, Hankins CA: The strong protective effect of circumcision against cancer of the penis.

    Adv Urol 2011, 1-21.

    Article ID 812368

    OpenURL

  147. Tobian AA, Serwadda D, Quinn TC, Kigozi G, Gravitt PE, Laeyendecker O, Charvat B, Ssempijja V, Riedesel M, Oliver AE, Nowak RG, Moulton LH, Chen MZ, Reynolds SJ, Wawer MJ, Gray RH: Male circumcision for the prevention of HSV-2 and HPV infections and syphilis.

    N Engl J Med 2009, 360:1298-1309. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  148. Gray RH, Kigozi G, Serwadda D, Makumbi F, Nalugoda F, Watya S, Moulton L, Chen MZ, Sewankambo NK, Kiwanuka N, Sempijja V, Lutalo T, Kagayii J, Wabwire-Mangen F, Ridzon R, Bacon M, Wawer MJ: The effects of male circumcision on female partners' genital tract symptoms and vaginal infections in a randomized trial in Rakai, Uganda.

    Am J Obstet Gynecol 2009, 200:42.e1-42.e7. Publisher Full Text OpenURL

  149. Tarnaud C, Lissouba P, Cutler E, Puren A, Taljaard D, Auvert B: Association of low-risk human papillomavirus infection with male circumcision in young men: results from a longitudinal study conducted in orange farm (South Africa).

    Infect Dis Obstet Gynecol 2011, 2011:567408. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  150. Lane T, Raymond HF, Dladla S, Rasethe J, Struthers H, McFarland W, McIntyre J: High HIV prevalence among men who have sex with men in Soweto, South Africa: Results from the Soweto Men's Study.

    AIDS Behav 2011, 15:626-634. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  151. Millett GA, Flores SA, Marks G, Reed JB, Herbst JH: Circumcision status and risk of HIV and sexually transmitted infections among men who have sex with men: a meta-analysis.

    JAMA 2008, 300:1674-1684. PubMed Abstract | Publisher Full Text OpenURL

  152. Wiysonge CS, Kongnyuy EJ, Shey M, Muula AS, Navti OB, Akl EA, Lo YR: Male circumcision for prevention of homosexual acquisition of HIV in men.

    Cochrane Database Syst Rev 2011, 6:CD007496. PubMed Abstract | Publisher Full Text OpenURL

  153. Schneider JA, Michaels S, Gandham SR, McFadden R, Liao C, Yeldandi VV, Oruganti G: A protective effect of circumcision among receptive male sex partners of Indian men who have sex with men.

    AIDS Behav 2011, in press. OpenURL

  154. Rennie S, Muula AS, Westreich D: MC and HIV prevention - ethical, medical and public health tradeoffs in low-income countries.

    J Med Ethics 2007, 33:357-361. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  155. Mehta SD, Gray RH, Auvert B, Moses S, Kigozi G, Taljaard D, Puren A, Agot K, Serwadda D, Parker CB, Wawer MJ, Bailey RC: Does sex in the early period after circumcision increase HIV-seroconversion risk? Pooled analysis of adult male circumcision clinical trials.

    AIDS 2009, 23:1557-1564. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  156. Cooper DA, Wodak AD, Morris BJ: The case for boosting infant male circumcision in the face of rising heterosexual transmission of HIV.

    Med J Aust 2010, 193:318-319. PubMed Abstract | Publisher Full Text OpenURL

  157. Green LW, Travis JW, McAllister RG, Peterson KW, Vardanyan AN, Craig A: Male circumcision and HIV prevention insufficient evidence and neglected external validity.

    Am J Prev Med 2010, 39:479-482. PubMed Abstract | Publisher Full Text OpenURL

  158. Banerjee J, Klausner JD, Halperin DT, Wamai R, Schoen EJ, Moses S, Morris BJ, Bailis SA, Venter F, Martinson N, Coates TJ, Gray G, Bowa K: Circumcision Denialism Unfounded and Unscientific.

    Am J Prev Med 2011, 40:e11-e12. PubMed Abstract | Publisher Full Text OpenURL

  159. Agot KE, Kiarie JN, Nguyen HQ, Odhiambo JO, Onyango TM, Weiss NS: Male circumcision in Siaya and Bondo districts, Kenya: prospective cohort study to assess behavioral disinhibition following circumcision.

    J Acquir Immune Defic Syndr 2007, 44:66-70. PubMed Abstract | Publisher Full Text OpenURL

  160. Mattson CL, Campbell RT, Bailey RC, Agot K, Ndinya-Achola JO, Moses S: Risk compensation is not associated with male circumcision in Kisumu, Kenya: a multi-faceted assessment of men enrolled in a randomized controlled trial.

    PLoS One 2008, 3:e2443. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  161. Bailey RC, Moses S, Parker CB, Agot K, Maclean I, Krieger JN, Williams CF, Ndinya-Achola JO: The protective effect of male circumcision is sustained for at least 42 months: results from the Kisumu, Kenya Trial.

    XVII International AIDS Conference 2008.

    Abstract #THAC05

    OpenURL

  162. Bailey RC, Moses S, Parker CB, Agot K, MacLean I, Krieger JN, Williams CFM, Ndinya-Achola JO: The protective effect of adult male circumcision against HIV acquisition is sustained for at least 54 months: results from the Kisumu, Kenya trial. In XVIII International AIDS Conference, Jul 18-23, 2010. Vienna; 2010.

    Abstract #FRLBC1

    OpenURL

  163. Kong X, Kigozi G, Ssempija V, Serwadda D, Nalugoda F, Makumbi F, Lutalo T, Watya S, Wawer M, R Gray R: Longer-term effects of male circumcision on HIV incidence and risk behaviors during post-trial surveillance in Rakai, Uganda.

    18th Conference on Retroviruses and Opportunistic Infections, Boston 2011.

    Abstract #36

    OpenURL

  164. Herman-Roloff A, Llewellyn E, Obiero W, Agot K, Ndinya-Achola J, Muraguri N, Bailey RC: Implementing voluntary medical male circumcision for HIV prevention in Nyanza Province, Kenya: Lessons learned during the first year.

    PLoS ONE 2011, 6:e18299. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  165. WHO/UNAIDS: [http://www.who.int/hiv/pub/malecircumcision/who_hiv_mc_opguide.pdf] webcite

    Operational guidance for scaling up male circumcision services for HIV prevention. Geneva: UNAIDS; OpenURL

  166. Potts M, Halperin DT, Kirby D, Swidler A, Marseille E, Klausner JD, Hearst N, Wamai RG, Kahn JG, Walsh J: Reassessing HIV prevention.

    Science 2008, 320:749-750. PubMed Abstract | Publisher Full Text OpenURL

  167. WHO/UNAIDS: [http://www.malecircumcision.org/documents/MC_country_12sept11a.pdf] webcite

    Progress in scale-up of male circumcision for HIV prevention in Eastern and Southern Africa: Focus on service delivery. OpenURL

  168. Gebbie KM: Science and policy: a perpetual dilemma.

    AIDS Reader 2009, 19:100-101. PubMed Abstract OpenURL

  169. Ministry of Health and Social Welfare, Government of Lesotho: [http://www.nas.org.ls/documents/MALE_CIRCUMCISION_REPORT-FINAL.pdf] webcite

    Male Circumcision in Lesotho: Situation Analysis Report. OpenURL

  170. Bugalo B: [http:/ / www.newsday.co.zw/ article/ 2011-06-12-government-targets-circu mcising-12m-males-by-2015] webcite

    Government targets circumcising 1.2m males by 2015. Newsday. 2011. OpenURL

  171. Dickson K, Farley T: Male circumcision scale-up. 17th Conference on Retroviruses and Opportunistic Infections (CROI); 2010.

    San Francisco. Abstract oral#62

    OpenURL

  172. Nyanza Provincial Task Force on Male Circumcision: [http:/ / www.malecircumcision.org/ programs/ documents/ Nyanza_Newsletter100210.pdf] webcite

    Nyanza Update: Quarterly Provincial Newsletter on the voluntary medical male circumcision program. 2009. OpenURL

  173. Patrick DM, Schneiderman J, Kinahan T, Pollock N, Ma'ayan S: [http:/ / www.bccdc.ca/ NR/ rdonlyres/ 8A389970-CA25-4212-ACE3-6374104AC85 B/ 0/ Epid_research_Integrating_MC_HIV_20 09_06_15.pdf] webcite

    Integrating Male Circumcision (MC) into HIV Prevention Efforts: Our Learning in Ethiopia, Kenya and Rwanda. Canadian Institute of Health Research; 2009. OpenURL

  174. WHO: [http://www.malecircumcision.org/programs/documents/mc_MOVE_2010_web.pdf] webcite

    Considerations for Implementing Models for Optimizing the Volume and Efficiency of Male Circumcision Services for HIV Prevention. OpenURL

  175. WHO: Task Shifting: Rational Redistribution of Tasks Among Health Workforce Teams: Global Recommendations and Guidelines. Geneva; 2008. OpenURL

  176. Mboera LEG, Massaga JJ, Senkoro KP, Kilima SP, Mayala BK, Msovela J, Shayo EH: [http:/ / malecircumcision.org/ programs/ documents/ Traditional_Providers_final_report1 .pdf] webcite

    Challenges and Opportunities for the involvement of Traditional Practitioners in Scaling up Safe Male Circumcision in the Context of HIV Prevention in Tanzania. National Institute for Medical Research. Dar es Salaam, Tanzania; 2009. OpenURL

  177. Wambura M, Mwanga JR, Mosha JF, Mshana G, Mosha F, Changalucha J: Acceptability of medical male circumcision in the traditionally circumcising communities in Northern Tanzania.

    BMC Public Health 2011, 11:373. PubMed Abstract | BioMed Central Full Text | PubMed Central Full Text OpenURL

  178. Morris BJ, Eley C: Male circumcision: An appraisal of current instrumentation. In: Biomedical Engineering.

    In Biomedical Engineering - From Theory to Applications Edited by Fazel-Rezai R. 2011.

    InTech

    OpenURL

  179. Masson P, Li PS, Barone MA, Goldstein M: The ShangRing device for simplified adult circumcision.

    Nat Rev Urol 2010, 7:638-642. PubMed Abstract | Publisher Full Text OpenURL

  180. Barone MA, Ndede F, Li PS, Masson P, Awori Q, Okech J, Cherutich P, Muraguri N, Perchal P, Lee R, Kim HH, Goldstein M: The Shang Ring device for adult male circumcision: a proof of concept study in Kenya.

    J Acquir Immune Defic Syndr 2011, 57:e7-e12. PubMed Abstract | Publisher Full Text OpenURL

  181. Decastro B, Gurski J, Peterson A: Adult template circumcision: a prospective, randomized, patient-blinded, comparative study evaluating the safety and efficacy of a novel circumcision device.

    Urology 2010, 76:810-814. PubMed Abstract | Publisher Full Text OpenURL

  182. Bitega JP, Ngeruka ML, Hategekimana T, Asiimwe A, Binagwaho A: Safety and efficacy study of the PrePex system for male circumcision. 18th Conference on Retroviruses and Opportunistic Infections, Boston; 2011.

    Abstract #1007

    OpenURL

  183. Peng Y-F, Cheng Y, Wang GY, Wang SQ, Jia C, Yang BH, Zhu R, Jian SC, Li QW, Geng DW: Clinical application of a new device for minimally invasive circumcision.

    Asian J Androl 2008, 10:447-454. PubMed Abstract | Publisher Full Text OpenURL

  184. Lagarde E, Taljaard D, Puren A, Auvert B: High rate of adverse events consecutive to circumcision of young male adults with the Tara KLamp technique. Results from a randomized trial conducted in South Africa.

    S Afr Med J 2009, 99:163-169. PubMed Abstract OpenURL

  185. WHO: [http:/ / www.malecircumcision.org/ programs/ documents/ MC_device_evaluation_framework_Feb1 1.pdf] webcite

    Framework for clinical evaluation of devices for adult male circumcision. 2011. OpenURL

  186. Global HIV Prevention Working Group: [http:/ / www.malecircumcision.org/ advocacy/ documents/ PWG_HIV_prevention_report_web.pdf] webcite

    Bringing HIV prevention to scale: an urgent global priority. 2007. OpenURL

  187. United Nations General Assembly: [http:/ / www.unaids.org/ en/ media/ unaids/ contentassets/ documents/ document/ 2011/ 06/ 20110610_UN_A-RES-65-277_en.pdf] webcite

    Political Declaration on HIV/AIDS: Intensifying our Efforts to Eliminate HIV/AIDS.

    Resolution adopted by the General Assembly on 10 June 2011

    OpenURL

  188. Kirby Institute [National Centre in HIV Epidemiology and Clinical Research]: [http:/ / www.med.unsw.edu.au/ NCHECRweb.nsf/ resources/ 2011/ $file/ KIRBY_ASR2011.pdf] webcite

    HIV/AIDS, Viral Hepatitis & Sexually Transmissible Infections in Australia Annual Surveillance Report. 2011. PubMed Abstract OpenURL

  189. Smith DK, Taylor A, Kilmarx PH, Sullivan P, Warner L, Kamb M, Bock N, Kohmescher B, Mastro TD: Male circumcision in the United States for the prevention of HIV infection and other adverse health outcomes: report from a CDC consultation.

    Public Health Rep 2010, 125(Suppl 1):72-82. PubMed Abstract | PubMed Central Full Text OpenURL

  190. Xu F, Markowitz LE, Sternberg MR, Aral SO: Prevalence of circumcision and herpes simplex virus type 2 infection in men in the United States: The National Health and Nutrition Examination Survey (NHANES), 1999-2004.

    Sex Transm Dis 2007, 34:479-484. PubMed Abstract | Publisher Full Text OpenURL

  191. McKinney CM, Klingler EJ, Paneth-Pollak R, Schillinger JA, Gwynn RC, Frieden TR: Prevalence of adult male circumcision in the general population and a population at increased risk for HIV/AIDS in New York City.

    Sex Transm Dis 2008, 35:814-817. PubMed Abstract | Publisher Full Text OpenURL

  192. Sutton MY, Jones RL, Wolitski RJ, Cleveland JC, Dean HD, Fenton KA: A review of the Centers for Disease Control and Prevention's response to the HIV/AIDS crisis among Blacks in the United States, 1981-2009.

    Am J Public Health 2009, 99(Suppl 2):S351-S359. PubMed Abstract | Publisher Full Text OpenURL

  193. Hall HI, Song R, Rhodes P, Prejean J, An Q, Lee LM, Karon J, Brookmeyer R, Kaplan EH, McKenna MT, Janssen RS, HIV Incidence Surveillance Group: Estimation of HIV incidence in the United States.

    JAMA 2008, 300:520-529. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  194. Centers for Disease Control and Prevention: Racial/ethnic disparities among children with diagnoses of perinatal HIV infection - 34 states, 2004-2007.

    MMWR 2010, 59:97-101. PubMed Abstract | Publisher Full Text OpenURL

  195. Centers for Disease Control and Prevention: Racial/ethnic disparities in diagnoses of HIV/AIDS -- 33 states, 2001-2005.

    MMWR 2007, 56:189-193. PubMed Abstract | Publisher Full Text OpenURL

  196. Grant RM, Lama JR, Anderson PL, McMahan V, Liu AY, Vargas L, Goicochea P, Casapía M, Guanira-Carranza JV, Ramirez-Cardich ME, Montoya-Herrera O, Fernández T, Veloso VG, Buchbinder SP, Chariyalertsak S, Schechter M, Bekker LG, Mayer KH, Kallás EG, Amico KR, Mulligan K, Bushman LR, Hance RJ, Ganoza C, Defechereux P, Postle B, Wang F, McConnell JJ, Zheng JH, Lee J, Rooney JF, Jaffe HS, Martinez AI, Burns DN, Glidden DV, iPrEx Study Team: Preexposure Chemoprophylaxis for HIV prevention in men who have sex with men.

    N Engl J Med 2010, 363:2587-2599. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  197. Abdool Karim Q, Abdool Karim SS, Frohlich JA, Grobler AC, Baxter C, Mansoor LE, Kharsany AB, Sibeko S, Mlisana KP, Omar Z, Gengiah TN, Maarschalk S, Arulappan N, Mlotshwa M, Morris L, Taylor D, CAPRISA 004 Trial Group: Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women.

    Science 2010, 329:1168-1174. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  198. Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, Kaewkungwal J, Chiu J, Paris R, Premsri N, Namwat C, de Souza M, Adams E, Benenson M, Gurunathan S, Tartaglia J, McNeil JG, Francis DP, Stablein D, Birx DL, Chunsuttiwat S, Khamboonruang C, Thongcharoen P, Robb ML, Michael NL, Kunasol P, Kim JH, MOPH-TAVEG Investigators: Vaccination with ALVAC and AIDSVAX to Prevent HIV-1 Infection in Thailand.

    N Engl J Med 2009, 361:2209-2220. PubMed Abstract | Publisher Full Text OpenURL

  199. Serwadda D, Gray RH, Sewankambo NK, Wabwire-Mangen F, Chen MZ, Quinn TC, Lutalo T, Kiwanuka N, Kigozi G, Nalugoda F, Meehan MP, Ashley Morrow R, Wawer MJ: Human immunodeficiency virus acquisition associated with genital ulcer disease and herpes simplex virus type 2 infection: a nested case-control study in Rakai, Uganda.

    J Infect Dis 2003, 188:1492-1497. PubMed Abstract | Publisher Full Text OpenURL

  200. Corey L, Wald A, Celum CL, Quinn TC: The effects of herpes simplex virus-2 on HIV-1 acquisition and transmission: a review of two overlapping epidemics.

    J Acquir Immune Defic Syndr 2004, 35:435-445. PubMed Abstract | Publisher Full Text OpenURL

  201. WHO: [http://www.who.int/hiv/pub/priority_interventions_web.pdf] webcite

    Priority interventions: HIV/AIDS prevention, treatment and care in the health sector. 2009. OpenURL