Circumcision and HIV
Encyclopedia
Over forty epidemiological studies have been conducted to investigate the relationship between male circumcision and HIV infection. Reviews of these studies have reached differing conclusions about whether circumcision could be used as a prevention method against HIV.
Experimental evidence was needed to establish a causal relationship between lack of circumcision and HIV, so three randomized controlled trials were commissioned as a means to reduce the effect of any confounding factors
. Trials took place in South Africa, Kenya
and Uganda
. All three trials were stopped early by their monitoring boards on ethical grounds, because those in the circumcised group had a lower rate of HIV contraction than the control group. The results showed that circumcision reduced vaginal-to-penile transmission of HIV by 60%, 53%, and 51%, respectively. A meta-analysis of the African randomised controlled trials found that the risk in circumcised males was 0.44 times that in uncircumcised males, and reported that 72 circumcisions would need to be performed to prevent one HIV infection. The authors also stated that using circumcision as a means to reduce HIV infection would, on a national level, require consistently safe sexual practices to maintain the protective benefit.
As a result of these findings, the WHO
and the Joint United Nations Programme on HIV/AIDS (UNAIDS) stated that male circumcision is an efficacious intervention for HIV prevention but should be carried out by well trained medical professionals and under conditions of informed consent (parents consent for their infant boys). Both the WHO and CDC
indicate that circumcision may not reduce HIV transmission from men to women, and that data is lacking for the transmission rate of men who engage in anal sex with a female partner. The joint WHO/UNAIDS recommendation also notes that circumcision only provides partial protection from HIV and should never replace known methods of HIV prevention. A newer study, published in PLoS in January, 2010, points out that gross changes in the penis's microbiome occurs following circumcision, and this may play a role in protection from HIV and other sexually transmitted diseases. A 2001 report of a study, which "was published as an abstract and presented at a conference", in MedPage Today, states that the "benefit of male circumcision for HIV prevention persists, even long after the procedure". However, they also insist that "these data and conclusions should be considered to be preliminary until published in a peer-reviewed journal."
A meta-analysis of data from fifteen observational studies of men who have sex with men
found "insufficient evidence that male circumcision protects against HIV infection or other STIs."
Some earlier reports had expressed the position that circumcision has little to no effect on HIV transmission among heterosexual couples. Furthermore, some have challenged the validity of the African randomized controlled trials, prompting a number of researchers to question the effectiveness of circumcision as an HIV prevention strategy.
were partly responsible for the continent's high rate of HIV infection. He did this via a letter to the New York State Journal of Medicine in August 1986. He also alleges that the late Aaron J. Fink stole his idea when Fink published a letter to the New England Journal of Medicine
entitled A possible explanation for heterosexual male infection with AIDS, in October 1986.
. Since then over 40 epidemiological studies have been conducted to investigate the relationship between circumcision and HIV infection.
In 1994, de Vincenzi and Mertens surveyed previous studies that had links between circumcision status and HIV; they surveyed 23 in total. They criticised the Cameron study saying that it may have suffered from selection bias.
In 1995 Ntozi noted: "There are now two schools of thought about the link between lack of circumcision and HIV infection in Africa. One school is that of Bongaarts et al. (1989), Moses et al. (n.d.) and Caldwell and Caldwell (1994) who use geographical distribution evidence to argue that the association between lack of circumcision and a high level of HIV infection in Africa is so convincing that the likelihood of a link should be recognized and taken into account where possible in the battle against AIDS. Moses et al. (n.d.) have gone further to recommend circumcision interventions for Africa. In contrast, De Vincenzi and Mertens (1994) argue that the evidence for an association, at least from small-scale surveys, is doubtful and hence not conclusive enough to qualify circumcision as an intervention.
Van Howe conducted a meta-analysis in 1999 and found circumcised men at a greater risk for HIV infection. He further speculated that circumcision may be responsible for the increased number of partners, and therefore, the increased risk. Van Howe's work was reviewed by O'Farrell and Egger (2000) who said Van Howe used an inappropriate method for combining studies, stating that re-analysis of the same data revealed that the presence of the foreskin was associated with increased risk of HIV infection (fixed effects OR 1.43, 95%CI 1.32 to 1.54; random effects OR 1.67, 1.25 to 2.24). Moses et al. (1999) also criticised Van Howe's paper, stating that his results were a case of "Simpson's paradox
, which is a type of confounding that can occur in epidemiological analyses when data from different strata with widely divergent exposure levels are combined, resulting in a combined measure of association that is not consistent with the results for each of the individual strata." They concluded that, contrary to Van Howe's assertion, the evidence that lack of circumcision increases the risk of HIV "appears compelling".
Weiss, Quigley and Hayes carried out a meta-analysis on circumcision and HIV in 2000 and found as follows: "Male circumcision is associated with a significantly reduced risk of HIV infection among men in sub-Saharan Africa, particularly those at high risk of HIV. These results suggest that consideration should be given to the acceptability and feasibility of providing safe services for male circumcision as an additional HIV prevention strategy in areas of Africa where men are not traditionally circumcised."
The USAID document summarised research as of September 2002. It states:
Siegried et al. (2003) surveyed 35 observational studies relating to HIV and circumcision: 16 conducted in the general population and 19 in high-risk populations. They state:
In 2005, Siegfried et al. published a review including 37 observational studies. Most studies indicated an association between lack of circumcision and increased risk of HIV, but the quality of evidence was judged insufficient to warrant implementation of circumcision as a public health measure. The authors stated that the results of the three randomised controlled trials then underway would therefore provide essential evidence about the effects of circumcision as an HIV intervention.
Kiwanuka et al.s (1996) study on the relationship between religion and HIV in rural Uganda was presented at the 1996 10th International AIDS Conference He said that: "Lower rates of HIV infection among Pentecostals
appear to be associated with less alcohol
consumption, sexual abstinence
and fewer sexual partners, whereas the low HIV prevalence in Muslim
s appears to be associated with low reported alcohol consumption and male circumcision." Muslims, despite having the lowest rate of sexual abstinence and the highest rate of having two or more sexual partners, had the lowest level of HIV infection compared with the other religious groups in the study (Catholics, Protestants
, and Pentecostals). The factor in common between the Muslims (14.5% seropositive) and the Pentecostals (14.6% seropositive) was the lower alcohol consumption rate in these two groups than amongst Protestants (19.2%) and Catholics (19.9%).
Kelly et al. (1999) investigated the age of male circumcision and risk of prevalent HIV infection in rural Uganda and found that circumcision before the age of 12 resulted in a reduction to 0.39 of the odds of being infected. The degree of protection varied with the age at which circumcision was performed. Those circumcised at between 13 and 20 years had an odds ratio of 0.46, and those circumcised after the age of 20 at an odds ratio of 0.78. They concluded: "Prepubertal circumcision is associated with reduced HIV risk, whereas circumcision after age 20 years is not significantly protective against HIV-1 infection."
Buvé and colleagues (1999) investigated the reasons why the HIV prevalence rate among pregnant women in many large towns in Central, East and southern Africa was higher (>30%) than in the cities and towns of most of West Africa (<10%). Between June 1997 and March 1998 surveys were carried out and blood samples were taken in 4 sites. Kisumu (Kenya) and Ndola (Zambia), in Central/East Africa, were selected as the towns with high HIV prevalence, while the low-prevalence towns in West Africa were Cotonou (Benin) and Yaoundé (Cameroon). "In conclusion, differences in the rate of HIV spread between the East African and West African cities studied cannot be explained away by differences in sexual behaviour alone. In fact, behavioural differences seem to be outweighed by differences in HIV transmission probability."
Bailey et al. (1999) interviewed 188 circumcised and 177 uncircumcised consenting Ugandan men in one of four native languages during April and May, 1997. Non-Muslim
circumcised men were found to have a higher risk profile than uncircumcised men. Muslims generally had a lower risk profile than other circumcised men except they were less likely to have ever used a condom or to have used a condom during the last sex encounter. Bailey et al. concluded that "these results suggest that differences between circumcised and uncircumcised men in their sex practices and hygienic behaviors do not account for the higher risk of HIV infection found among uncircumcised men. Further consideration should be given to male circumcision as a prevention strategy in areas of high prevalence of HIV and other sexually transmitted diseases. Studies of the feasibility and acceptability of male circumcision in traditionally non-circumcising societies are warranted."
Bonner (2001) reserved caution over using circumcision to prevent HIV: "Until we know why and how circumcision is protective, exactly what the relationship is between circumcision status and other STIs, and whether the effect
seen in high-risk populations is generalisable to other groups, the wisest course is to recommend risk
reduction strategies of proven efficacy, such as condom use."
At the 14th International AIDS conference in 2002, Changedia and Gilada reported that "Though circumcision offers protection in acquisition of HIV infection, our findings reveal that it does not reduce transmission of HIV in conjugal settings." Hunter et al. (1994), however, report that "Women whose husband or usual sex partner was uncircumcised had a threefold increase in risk of HIV, and this risk was present in almost all strata of potential confounding factors." Fonck et al. (2000) reported that "Partners of circumcised men had less-prevalent HIV infection."
The prevalence of circumcision varies across Africa. Studies have been conducted to assess the acceptability of promoting circumcision in place where they traditionally do not circumcise. In 2007, country consultations and planning to scale up male circumcision programmes took place in Botswana
, Kenya
, Lesotho
, Malawi
, Mozambique
, Namibia
, Rwanda
, South Africa
, Swaziland
, Uganda
, Tanzania
, Zambia
and Zimbabwe
. Kebaabetswe et al. carried out interviews in nine geographically representative locations to determine the acceptability of male circumcision as well as the preferred age and setting for male circumcision in Botswana. Their conclusion was "Male circumcision appears to be highly acceptable in Botswana. The option for safe circumcision should be made available to parents in Botswana for their male children. Circumcision might also be an acceptable option for adults and adolescents, if its efficacy as an HIV prevention strategy among sexually active people is supported by clinical trials." Boyle criticised Kebaabetswe et al.s proposal to introduce infant circumcision to Botswana saying that: "The proposal by Kebaabetswe and colleagues for the introduction of circumcision into Botswana is seriously flawed, and is irresponsible in failing to place the emphasis on safe sex practices. As described here, there are many medical, sexual, psychological, social, human rights, ethical, and legal aspects that must be considered. Reliance on circumcision to prevent HIV transmission is wishful fantasy, and can only result in a calamitous worsening of the HIV-AIDS epidemic."
Bailey et al. looked at the possible adverse effects of introducing male circumcision on a public health scale and the post operative satisfaction levels of 380 circumcisions on 18-24 year old consenting men. As to satisfaction; "At 30 days post-surgery, 99.3% of men reported being very satisfied and 0.7% somewhat satisfied with circumcision. None were dissatisfied." And with regard to adverse effects; "All were mild or moderate and resolved within hours or several days of detection." Their findings were presented at the 15th International AIDS Conference
held in Bangkok in 2004.
At the 15th International AIDS Conference in 2004, Connolly et al. presented their report detailing the effects of circumcision in South Africa. They reported that, among racial groups, "circumcised Blacks showed similar rates of HIV as uncircumcised Blacks, (OR: 0.8, p = 0.4) however other racial groups showed a strong protective effect, (OR: 0.3, p = 0.01)." They added "When the data are further stratified by age of circumcision, there is a slight protective effect between early circumcision and HIV among Blacks, OR: 0.7, p = 0.4." They conclude that "in general, circumcision offers slight protection." At the same conference, Thomas et al. (2004) reported that "male circumcision is not associated with HIV or STI prevention in a U.S. Navy population."
Reynolds et al. (2004) found that male circumcision was strongly protective against HIV-1 infection with circumcised men being almost seven times less at risk of HIV infection than uncircumcised men. They further state that: "The specificity of this relation suggests a biological rather than behavioural explanation for the protective effect of male circumcision against HIV-1."
Baeten et al. (2005) found that uncircumcised men were at a greater than twofold increased risk of acquiring HIV per sex act when compared with circumcised men. They conclude as follows:
At the 2006 Conference on Retroviruses and Opportunistic Infections Quinn et al. presented their study, conducted in Rakai
, Uganda
, which observed a 30% reduction in male-to-female HIV transmission, suggesting some protective effect for the female partner.
Newell and Bärnighausen (2007) also stated there was "firm evidence that the risk of acquiring HIV is halved by male circumcision."
Mishra et al. (2006) used data collected from the Demographic and Health Surveys
and found that HIV prevalence was "considerably higher in urban areas and for women, especially at younger ages. Adults in wealthier households, in polygamous unions, being widowed/divorced/separated, having multiple sex partners, and having reported STIs had higher HIV rates than other adults. No consistent relationship between male circumcision and HIV risk was observed in most countries."
Way et al. (2006) also used data from Demographic and Health Surveys in Burkina Faso
, Cameroon
, Ghana
, Kenya
, Lesotho
, and Malawi
and from AIDS Indicator Surveys in Tanzania
and Uganda
to conduct his study. They found that "With age, education, wealth status, and a number of sexual and other behavioral risk factors controlled statistically, in only one of the eight countries were circumcised men at a significant advantage. In the other seven countries, the association between circumcision and HIV status was not statistically significant for the male population as a whole."
Garenne (2006) has doubts about circumcision's value in reducing HIV, and Talbott (2007), in a controversial paper stated that cross country regression data pointed to prostitution as the key factor in the AIDS epidemic rather than circumcision. World Health Organization AIDS Prevention Team official Tim Farley disagreed with the findings of the paper, while Chris Surridge, PLoS One's managing editor, defended its publication. In 1999 the American Medical Association had stated, "behavioral factors are far more important in preventing these infections than the presence or absence of a foreskin."
If proper hygienic procedures are not adhered to, the circumcision operation itself can spread HIV. Brewer et al. (2007) report, "[circumcised] male and female virgins were substantially more likely to be HIV infected than uncircumcised virgins. Among adolescents, regardless of sexual experience, circumcision was just as strongly associated with prevalent HIV infection. However, uncircumcised adults were more likely to be HIV positive than circumcised adults." They concluded: "HIV transmission may occur through circumcision-related blood exposures in eastern and southern Africa."
Van Howe et al. criticise the drive to promote circumcision in Africa, asking "Why are circumcision proponents expending so much time and energy promoting mass circumcision to North Americans when their supposed aim is to prevent HIV in Africa? The circumcision rate is declining in the US, especially on the west coast; the two North American national paediatric organisations have elected not to endorse the practice, and the practice’s legality has been questioned in both the medical and legal literature. ‘Playing the HIV card’ misdirects the fear understandably generated in North Americans by the HIV/AIDS pandemic into a concrete action: the perpetuation of the outdated practice of neonatal circumcision."
Connolly et al. (2008) found that "circumcision had no protective effect in the prevention of HIV transmission. This is a concern, and has implications for the possible adoption of the mass male circumcision strategy both as a public health policy and an HIV prevention strategy."
Sidler et al. (2008) say that using neonatal non-therapeutic circumcision to combat the HIV crisis in Africa is neither medically nor ethically justifiable. Furthermore, promoting circumcision might worsen the problem by creating a false sense of security and therefore undermining safe sex practices. Education, female economic independence, safe sex practices and consistent condom use are proven effective measures against HIV transmission.
Boiley et al. (2008) found that the protection of circumcision against STI contributes little to the overall effect of circumcision on HIV.
Lagarde (2003) stated that "More than 70% of the non-circumcised men (NCM) stated that they would want to be circumcised if MC were proved to protect against sexually transmitted diseases (STD)." Lagarde cautioned that "Our results strongly suggest that interventions including MC should carefully address the false sense of security that it may provide."
A 2008 meta-analysis of 15 observational studies, including 53,567 gay and bisexual men from the United States, Britain, Canada, Australia, India, Taiwan, Peru and the Netherlands (52% circumcised), found that the rate of HIV infection was non-significantly lower among men who were circumcised compared with those who were uncircumcised. For men who engaged primarily in insertive anal sex, a protective effect was observed, but it too was not statistically significant. Observational studies included in the meta-analysis that were conducted prior to the introduction of highly active antiretroviral therapy in 1996 demonstrated a statistically significant protective effect for circumcised MSM against HIV infection. In response to the meta-analysis by Millett et al., Vermund and Qian note that "circumcision would likely be insufficiently efficient to be universally effective in reducing HIV risk, and will have to be combined with other prevention modalities to have a substantial and sustained prevention effect."
has a higher rate of adult HIV infection than anywhere else in the world. Three randomised controlled trials
were commissioned in Africa to investigate whether circumcision could lower the rate of HIV contraction.
The first study to be published was named ANRS-1265. It was funded by the French government’s research agency, Agence Nationale de Recherches sur la SIDA (ANRS) and carried out in Orange Farm, Gauteng
in South Africa
. The purpose was to test the effect of adult male circumcision on HIV acquisition.
The principal investigator was Dr. Bertran Auvert of Versailles University. The study enrolled 3,274 men aged 18–24. The participants were split into two equal groups. One group was circumcised straight away; the other group, serving as a control, was to be circumcised 21 months later. 146 of the original participants were found to have HIV at the start of the trial - to avoid stigmatization, they were not excluded. It was planned that all the men would visit the research clinic four times during this 21-month period, and that they would be tested for HIV each time. They were instructed not to have sex for six weeks after the operation, and asked at each clinic visit to provide detailed information about their sexual activity. The circumcision procedure used was the forceps-guided method http://www.phru.co.za/pdf/circumcision/pitfalls.pdf, carried out by three local general practitioners in their surgical offices. After 17 months, 20 men had contracted HIV in the circumcised group and 49 in the control group. The trial was halted on ethical grounds. The results of the trial were published in November 2005.
The authors said, “Male circumcision provides a degree of protection against acquiring HIV infection, equivalent to what a vaccine of high efficacy would have achieved. Male circumcision may provide an important way of reducing the spread of HIV infection in sub-Saharan Africa.”
Williams et al.(2006) looked at the potential impact of circumcision on HIV in Africa, based upon the South African RCT, saying that that male circumcision (MC) could substantially reduce the burden of HIV in Africa, particularly in southern Africa where the existing prevalence of male circumcision is low and the existing prevalence of HIV is high. More specifically it predicted that if full coverage with MC was achieved in sub-Saharan Africa over the next ten years, MC could prevent approximately 2.0 (1.1 to 3.8) million new HIV infections over that ten year period and a further 3.7 million in the ten years after that.
The above conclusions drawn from the Orange Farm study have been criticised by Michel Garenne (2006) of the Institut Pasteur. In his critique, published on the PLoS Journal of Medicine, he concludes that: "'male circumcision should be regarded as an important public health intervention for preventing the spread of HIV' appears overstated. Even though large-scale male circumcision could avert a number of HIV infections, theoretical calculations and empirical evidence show that it is unlikely to have a major public health impact, apart from the fact that achieving universal male circumcision is likely to be more difficult than universal vaccination coverage or universal contraceptive use."
Mills and Siegfried (2006) point out that trials that are stopped early tend to over estimate treatment effects.
They argued that a meta-analysis should be done before further feasibility studies are done.
The NIAID
, part of the NIH
, supported two further trials, conducted in Kenya and in Uganda. The primary objectives of these studies were to determine whether adult male circumcision can be administered safely, and whether it would reduce the risk of acquiring HIV infection through heterosexual contact. After an initial HIV screening and a medical exam, eligible men were randomly assigned either to receive circumcision immediately or to wait two years before circumcision. All participants were closely followed for two years to collect information about their health, sexual activity, and their and their partners’ attitudes about circumcision; to counsel participants in HIV prevention and safe sex practices; and to check the HIV status of the volunteer. Participants in the Kenyan study were scheduled for six visits over the two-year follow-up, compared with four visits for the Ugandan trial participants. In addition to the study visits, men enrolled in the Kenyan trial were encouraged to receive all of their outpatient health care at the study clinics, which enabled researchers to collect information on the safety of the procedure and the number of other sexually transmitted diseases the men had during follow-up.
The Kenyan trial, also known as the UNIM trial (Universities of Nairobi, Illinois and Manitoba trial), began in February 2002, in Kisumu
, Kenya
. It was a collaborative effort between US, Canadian and Kenyan researchers, led by Dr. Robert Bailey, of the University of Illinois. Also involved were Stephen Moses, University of Manitoba
, Jeckoniah Ndinya-Achola, University of Nairobi
, and Kwango Agot, UNIM. The trial was funded by the NIAID and the Canadian Institutes of Health Research
. This trial enrolled 2,784 men between 18 and 24 years old. The participants were assessed by HIV testing, medical examinations, and behavioural interviews during follow-ups at 1, 3, 6, 12, 18, and 24 months. The circumcision procedure used in the Ugandan trial is known as the sleeve method and takes about 30 minutes. The Ugandan trial used cauterization of the blood vessels to control bleeding and stitches to close the wound. 22 men in the intervention group and 47 in the control group had tested positive for HIV when the study was stopped on ethical grounds.
The Ugandan trial began August, 2003 in Rakai
, Uganda
, with 4,996 men aged between 15 and 49 years old. It was led by Ronald Gray and Maria Wawer of Johns Hopkins Bloomberg School of Public Health
and David Serwadda and Nelson Sewankambo of Makerere University
in Kampala
, Uganda. The circumcision procedure used in the Kenyan trial was the foreskin clamp method. The Kenyan trial procedure took about 25 minutes and used stitches to control bleeding and improve wound closure. Trained and certified physicians performed the circumcisions in well-equipped operating rooms. Post-operative follow-up visits were scheduled at 24–48 hours, 5–9 days, and 4–6 weeks. HIV testing, physical examination, and interviews were repeated at 4–6 weeks, 6-, 12-, and 24-month follow-up visits. After 24 months, 964 of the original 2387 men of the circumcised men had been retained of whom 22 had contracted HIV. 980 of the 2430 uncircumcised men had been retained of whom 45 had contracted HIV.
Both trials were stopped early on December 13, 2006 on ethical grounds after it found that those belonging to the control group had a greater number of men with HIV than the circumcised group.
On Wednesday, March 28, 2007, the World Health Organisation (WHO) and UNAIDS issued joint recommendations concerning male circumcision and HIV/AIDS. These recommendations are:
Kim Dickson, coordinator of the working group that authored the report, commented:
The World Health Organization (WHO) said: “Although these results demonstrate that male circumcision reduces the risk of men becoming infected with HIV, the UN agencies emphasize that it does not provide complete protection against HIV infection. Circumcised men can still become infected with the virus and, if HIV-positive, can infect their sexual partners. Male circumcision should never replace other known effective prevention methods and should always be considered as part of a comprehensive prevention package, which includes correct and consistent use of male or female condoms, reduction in the number of sexual partners, delaying the onset of sexual relations, and HIV testing and counselling.”
Others have also expressed concern that some may mistakenly believe they will be fully protected against HIV through circumcision and see circumcision as a safe alternative to other forms of protection, such as condoms.
Dowsett et al. urged caution over using circumcision as a HIV prevention strategy saying that there were still questions that needed to be answered: "We need to investigate the effects of those other social and contextual factors that will be in play in real world settings – because the effectiveness of male circumcision will not be generated by the efficacy of the surgery alone." He contrasts the preventative effect of circumcision taken from the RCT's (55%) with the preventative effect of condoms (80-90%). He criticises the fact that the trials were not double-blinded - the participants knew their circumcision status and so this could have affected how the men responded behaviourally, psychologically and sexually. He criticised the randomisation measures used in the trial: sexual practices (number of partners, condom use) and sexual health measures (presence of STIs), saying that "Effective measures were not used, and differences related to sexual subjectivity, such as sexual network participation, pleasure preferences, body image, sexual history effects (e.g. abuse), partner preferences (younger, older, peers, groups) and so on were never assessed or analysed." He also asks how the extensive counselling and education might have influenced the participants' sexual activity. He adds that "all participants were subject to
regular monitoring (e.g. behaviour surveys, clinical check-ups), which clearly might have enhanced compliance with suggested safety regimes and lowered risk-taking during the follow-up period. Such compliance cannot be
guaranteed in real world settings." He also said the trials were subject to the Hawthorne effect
.
An interim analysis from the Rakai Health Sciences Program in Uganda suggested that newly circumcised HIV positive men may be more likely to spread HIV to their female partners if they have sexual intercourse before the wound is fully healed. “Because the total number of men who resumed sex before certified wound healing is so small, the finding of increased transmission after surgery may have occurred by chance alone. However, we need to err on the side of caution to protect women in the context of any future male circumcision programme,” said Maria Wawer, the study's principal investigator.
Kalichman et al. (2007) argue that any protective effects circumcision could offer would be partially offset by increased HIV risk behavior, or “risk compensation" including reduction in condom use or increased numbers of sex partners. They note that circumcised men in the South African trial had 18% more sexual contacts than uncircumcised men at follow-up. They also said that because participants were given ongoing risk-reduction counseling and free condoms, it "reduced the utility of these trials for estimating the potential behavioral impact of male circumcision when implemented in a natural setting." They also criticised current models for failing to account for increased HIV risk behaviour. Increased HIV risk behaviour would mean more women would be infected which would consequently increase the risk of men. It would also mean that non-HIV STI's, which have been associated with increased HIV risk, would increase. Green et al. (2008) also disagree with using circumcision to prevent HIV, citing similar reasons.
Published meta-analyses, using data from the RCTs, have estimated the summary relative risk
at 0.42 (95% CI
0.31-0.57), 0.44 (0.33-0.60) and 0.43 (0.32-0.59). (rate of HIV infection in circumcised divided by rate in uncircumcised men). Weiss et al. report that meta-analysis of "as-treated" figures from RCTs reveals a stronger protective effect (0.35; 95% CI 0.24-0.54) than if "intention-to-treat" figures are used. Byakika-Tusiime also estimated a summary relative risk of 0.39 (0.27-0.56) for observational studies, and 0.42 (0.33-0.53) overall (including both observational and RCT data). Weiss et al. report that the estimated relative risk using RCT data was "identical" to that found in observational studies (0.42). Byakika-Tusiime states that available evidence satisfies six of Hill's criteria, and concludes that the results of her analysis "provide unequivocal evidence that circumcision plays a causal role in reducing the risk of HIV infection among men." Mills et al. conclude that circumcision is an "effective strategy for reducing new male HIV infections", but caution that consistently safe sexual practices will be required to maintain the protective effect at the population level. Weiss et al. conclude that the evidence from the trials is conclusive, but that challenges to implementation remain, and will need to be faced.
s. Disease elimination was considered feasible when all interventions were combined. Hallet et al. predicted "dramatic" reductions in HIV if circumcision were scaled up alongside behaviour change programmes.
Studies of the cost-effectiveness of circumcision programmes have been similarly mixed. Kahn et al. studied sub-Saharan African settings with a high or moderate HIV prevalence, reporting that adult circumcision is "likely to be a cost-effective HIV prevention strategy" even when deployed among only a small fraction of the population. The authors concluded that circumcision "generates large net savings after adjustment for averted HIV medical costs". White et al. concluded that circumcision "is a cost-saving intervention in a wide range of scenarios of HIV and initial circumcision prevalence but the United Nations Joint Programme on HIV/AIDS/WHO recommended target age group should be widened to include older HIV-uninfected men and counselling should be targeted at both newly and already circumcised men to minimize risk compensation". The UNAIDS/WHO/SACEMA Expert Group on Modelling the Impact and Cost of Male Circumcision for HIV Prevention found "large benefits" of circumcision in settings with high HIV prevalence and low circumcision prevalence. The Group estimated "one HIV infection being averted for every five to 15 male circumcisions performed, and costs to avert one HIV infection ranging from US$150 to US$900 using a 10-y time horizon". McAllister et al. estimated that consistent condom use is 95 times more cost effective than circumcision at reducing the rate of HIV in sub-Saharan Africa; the World Health Organisation states that circumcision is "highly cost-effective" in comparison to other HIV interventions when data from the South African trial are used, but less cost-effective when data from the Ugandan trial are used.
, produced by Langerhans cells, is a natural barrier to HIV-1 transmission by Langerhans cells.
Dowsett (2007) questioned why it was just males that were being encouraged to circumcise: "Langerhans cells occur in the clitoris
, the labia and in other parts of both male and female genitals, and no one is talking of removing these in the name of HIV prevention."
Experimental evidence was needed to establish a causal relationship between lack of circumcision and HIV, so three randomized controlled trials were commissioned as a means to reduce the effect of any confounding factors
Confounding
In statistics, a confounding variable is an extraneous variable in a statistical model that correlates with both the dependent variable and the independent variable...
. Trials took place in South Africa, Kenya
Kenya
Kenya , officially known as the Republic of Kenya, is a country in East Africa that lies on the equator, with the Indian Ocean to its south-east...
and Uganda
Uganda
Uganda , officially the Republic of Uganda, is a landlocked country in East Africa. Uganda is also known as the "Pearl of Africa". It is bordered on the east by Kenya, on the north by South Sudan, on the west by the Democratic Republic of the Congo, on the southwest by Rwanda, and on the south by...
. All three trials were stopped early by their monitoring boards on ethical grounds, because those in the circumcised group had a lower rate of HIV contraction than the control group. The results showed that circumcision reduced vaginal-to-penile transmission of HIV by 60%, 53%, and 51%, respectively. A meta-analysis of the African randomised controlled trials found that the risk in circumcised males was 0.44 times that in uncircumcised males, and reported that 72 circumcisions would need to be performed to prevent one HIV infection. The authors also stated that using circumcision as a means to reduce HIV infection would, on a national level, require consistently safe sexual practices to maintain the protective benefit.
As a result of these findings, the WHO
Who
Who may refer to:* Who , an English-language pronoun* who , a Unix command* Who?, one of the Five Ws in journalism- Art and entertainment :* Who? , a 1958 novel by Algis Budrys...
and the Joint United Nations Programme on HIV/AIDS (UNAIDS) stated that male circumcision is an efficacious intervention for HIV prevention but should be carried out by well trained medical professionals and under conditions of informed consent (parents consent for their infant boys). Both the WHO and CDC
Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...
indicate that circumcision may not reduce HIV transmission from men to women, and that data is lacking for the transmission rate of men who engage in anal sex with a female partner. The joint WHO/UNAIDS recommendation also notes that circumcision only provides partial protection from HIV and should never replace known methods of HIV prevention. A newer study, published in PLoS in January, 2010, points out that gross changes in the penis's microbiome occurs following circumcision, and this may play a role in protection from HIV and other sexually transmitted diseases. A 2001 report of a study, which "was published as an abstract and presented at a conference", in MedPage Today, states that the "benefit of male circumcision for HIV prevention persists, even long after the procedure". However, they also insist that "these data and conclusions should be considered to be preliminary until published in a peer-reviewed journal."
A meta-analysis of data from fifteen observational studies of men who have sex with men
Men who have sex with men
Men who have sex with men are male persons who engage in sexual activity with members of the same sex, regardless of how they identify themselves; many men choose not to accept sexual identities of homosexual or bisexual...
found "insufficient evidence that male circumcision protects against HIV infection or other STIs."
Some earlier reports had expressed the position that circumcision has little to no effect on HIV transmission among heterosexual couples. Furthermore, some have challenged the validity of the African randomized controlled trials, prompting a number of researchers to question the effectiveness of circumcision as an HIV prevention strategy.
Earliest appearance in the literature
According to Alcena, it was he who first hypothesised that low rates of circumcision in AfricaAfrica
Africa is the world's second largest and second most populous continent, after Asia. At about 30.2 million km² including adjacent islands, it covers 6% of the Earth's total surface area and 20.4% of the total land area...
were partly responsible for the continent's high rate of HIV infection. He did this via a letter to the New York State Journal of Medicine in August 1986. He also alleges that the late Aaron J. Fink stole his idea when Fink published a letter to the New England Journal of Medicine
New England Journal of Medicine
The New England Journal of Medicine is an English-language peer-reviewed medical journal published by the Massachusetts Medical Society. It describes itself as the oldest continuously published medical journal in the world.-History:...
entitled A possible explanation for heterosexual male infection with AIDS, in October 1986.
Observational studies
In 1989 Cameron found uncircumcised men 8.2 times more likely to have HIVHIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
. Since then over 40 epidemiological studies have been conducted to investigate the relationship between circumcision and HIV infection.
In 1994, de Vincenzi and Mertens surveyed previous studies that had links between circumcision status and HIV; they surveyed 23 in total. They criticised the Cameron study saying that it may have suffered from selection bias.
In 1995 Ntozi noted: "There are now two schools of thought about the link between lack of circumcision and HIV infection in Africa. One school is that of Bongaarts et al. (1989), Moses et al. (n.d.) and Caldwell and Caldwell (1994) who use geographical distribution evidence to argue that the association between lack of circumcision and a high level of HIV infection in Africa is so convincing that the likelihood of a link should be recognized and taken into account where possible in the battle against AIDS. Moses et al. (n.d.) have gone further to recommend circumcision interventions for Africa. In contrast, De Vincenzi and Mertens (1994) argue that the evidence for an association, at least from small-scale surveys, is doubtful and hence not conclusive enough to qualify circumcision as an intervention.
Van Howe conducted a meta-analysis in 1999 and found circumcised men at a greater risk for HIV infection. He further speculated that circumcision may be responsible for the increased number of partners, and therefore, the increased risk. Van Howe's work was reviewed by O'Farrell and Egger (2000) who said Van Howe used an inappropriate method for combining studies, stating that re-analysis of the same data revealed that the presence of the foreskin was associated with increased risk of HIV infection (fixed effects OR 1.43, 95%CI 1.32 to 1.54; random effects OR 1.67, 1.25 to 2.24). Moses et al. (1999) also criticised Van Howe's paper, stating that his results were a case of "Simpson's paradox
Simpson's paradox
In probability and statistics, Simpson's paradox is a paradox in which a correlation present in different groups is reversed when the groups are combined. This result is often encountered in social-science and medical-science statistics, and it occurs when frequencydata are hastily given causal...
, which is a type of confounding that can occur in epidemiological analyses when data from different strata with widely divergent exposure levels are combined, resulting in a combined measure of association that is not consistent with the results for each of the individual strata." They concluded that, contrary to Van Howe's assertion, the evidence that lack of circumcision increases the risk of HIV "appears compelling".
Weiss, Quigley and Hayes carried out a meta-analysis on circumcision and HIV in 2000 and found as follows: "Male circumcision is associated with a significantly reduced risk of HIV infection among men in sub-Saharan Africa, particularly those at high risk of HIV. These results suggest that consideration should be given to the acceptability and feasibility of providing safe services for male circumcision as an additional HIV prevention strategy in areas of Africa where men are not traditionally circumcised."
The USAID document summarised research as of September 2002. It states:
- A systematic review and meta-analysis of 28 published studies by the London School of Hygiene and Tropical Medicine, published in the journal AIDS in 2000, found that circumcised men are less than half as likely to be infected by HIV as uncircumcised men. A subanalysis of 10 African studies found a 71 percent reduction among higher-risk men. A September 2002 update considered the results of these 28 studies plus an additional 10 studies and, after controlling for various potentially confounding religious, cultural, behavioral, and other factors, had similarly robust findings. Recent laboratory studies in Chicago found HIV uptake in the inner foreskin tissue to be up to nine times more efficient than in a control sample of cervical tissue.
Siegried et al. (2003) surveyed 35 observational studies relating to HIV and circumcision: 16 conducted in the general population and 19 in high-risk populations. They state:
- We found insufficient evidence to support an interventional effect of male circumcision on HIV acquisition in heterosexual men. The results from existing observational studies show a strong epidemiological association between male circumcision and prevention of HIV, especially among high-risk groups. However, observational studies are inherently limited by confounding which is unlikely to be fully adjusted for. In the light of forthcoming results from RCTs, the value of IPD analysis of the included studies is doubtful. The results of these trials will need to be carefully considered before circumcision is implemented as a public health intervention for prevention of sexually transmitted HIV.
In 2005, Siegfried et al. published a review including 37 observational studies. Most studies indicated an association between lack of circumcision and increased risk of HIV, but the quality of evidence was judged insufficient to warrant implementation of circumcision as a public health measure. The authors stated that the results of the three randomised controlled trials then underway would therefore provide essential evidence about the effects of circumcision as an HIV intervention.
Kiwanuka et al.s (1996) study on the relationship between religion and HIV in rural Uganda was presented at the 1996 10th International AIDS Conference He said that: "Lower rates of HIV infection among Pentecostals
Pentecostalism
Pentecostalism is a diverse and complex movement within Christianity that places special emphasis on a direct personal experience of God through the baptism in the Holy Spirit, has an eschatological focus, and is an experiential religion. The term Pentecostal is derived from Pentecost, the Greek...
appear to be associated with less alcohol
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
consumption, sexual abstinence
Sexual abstinence
Sexual abstinence is the practice of refraining from some or all aspects of sexual activity for medical, psychological, legal, social, philosophical or religious reasons.Common reasons for practicing sexual abstinence include:*poor health - medical celibacy...
and fewer sexual partners, whereas the low HIV prevalence in Muslim
Muslim
A Muslim, also spelled Moslem, is an adherent of Islam, a monotheistic, Abrahamic religion based on the Quran, which Muslims consider the verbatim word of God as revealed to prophet Muhammad. "Muslim" is the Arabic term for "submitter" .Muslims believe that God is one and incomparable...
s appears to be associated with low reported alcohol consumption and male circumcision." Muslims, despite having the lowest rate of sexual abstinence and the highest rate of having two or more sexual partners, had the lowest level of HIV infection compared with the other religious groups in the study (Catholics, Protestants
Protestantism
Protestantism is one of the three major groupings within Christianity. It is a movement that began in Germany in the early 16th century as a reaction against medieval Roman Catholic doctrines and practices, especially in regards to salvation, justification, and ecclesiology.The doctrines of the...
, and Pentecostals). The factor in common between the Muslims (14.5% seropositive) and the Pentecostals (14.6% seropositive) was the lower alcohol consumption rate in these two groups than amongst Protestants (19.2%) and Catholics (19.9%).
Kelly et al. (1999) investigated the age of male circumcision and risk of prevalent HIV infection in rural Uganda and found that circumcision before the age of 12 resulted in a reduction to 0.39 of the odds of being infected. The degree of protection varied with the age at which circumcision was performed. Those circumcised at between 13 and 20 years had an odds ratio of 0.46, and those circumcised after the age of 20 at an odds ratio of 0.78. They concluded: "Prepubertal circumcision is associated with reduced HIV risk, whereas circumcision after age 20 years is not significantly protective against HIV-1 infection."
Buvé and colleagues (1999) investigated the reasons why the HIV prevalence rate among pregnant women in many large towns in Central, East and southern Africa was higher (>30%) than in the cities and towns of most of West Africa (<10%). Between June 1997 and March 1998 surveys were carried out and blood samples were taken in 4 sites. Kisumu (Kenya) and Ndola (Zambia), in Central/East Africa, were selected as the towns with high HIV prevalence, while the low-prevalence towns in West Africa were Cotonou (Benin) and Yaoundé (Cameroon). "In conclusion, differences in the rate of HIV spread between the East African and West African cities studied cannot be explained away by differences in sexual behaviour alone. In fact, behavioural differences seem to be outweighed by differences in HIV transmission probability."
Bailey et al. (1999) interviewed 188 circumcised and 177 uncircumcised consenting Ugandan men in one of four native languages during April and May, 1997. Non-Muslim
Muslim
A Muslim, also spelled Moslem, is an adherent of Islam, a monotheistic, Abrahamic religion based on the Quran, which Muslims consider the verbatim word of God as revealed to prophet Muhammad. "Muslim" is the Arabic term for "submitter" .Muslims believe that God is one and incomparable...
circumcised men were found to have a higher risk profile than uncircumcised men. Muslims generally had a lower risk profile than other circumcised men except they were less likely to have ever used a condom or to have used a condom during the last sex encounter. Bailey et al. concluded that "these results suggest that differences between circumcised and uncircumcised men in their sex practices and hygienic behaviors do not account for the higher risk of HIV infection found among uncircumcised men. Further consideration should be given to male circumcision as a prevention strategy in areas of high prevalence of HIV and other sexually transmitted diseases. Studies of the feasibility and acceptability of male circumcision in traditionally non-circumcising societies are warranted."
Bonner (2001) reserved caution over using circumcision to prevent HIV: "Until we know why and how circumcision is protective, exactly what the relationship is between circumcision status and other STIs, and whether the effect
seen in high-risk populations is generalisable to other groups, the wisest course is to recommend risk
reduction strategies of proven efficacy, such as condom use."
At the 14th International AIDS conference in 2002, Changedia and Gilada reported that "Though circumcision offers protection in acquisition of HIV infection, our findings reveal that it does not reduce transmission of HIV in conjugal settings." Hunter et al. (1994), however, report that "Women whose husband or usual sex partner was uncircumcised had a threefold increase in risk of HIV, and this risk was present in almost all strata of potential confounding factors." Fonck et al. (2000) reported that "Partners of circumcised men had less-prevalent HIV infection."
The prevalence of circumcision varies across Africa. Studies have been conducted to assess the acceptability of promoting circumcision in place where they traditionally do not circumcise. In 2007, country consultations and planning to scale up male circumcision programmes took place in Botswana
Botswana
Botswana, officially the Republic of Botswana , is a landlocked country located in Southern Africa. The citizens are referred to as "Batswana" . Formerly the British protectorate of Bechuanaland, Botswana adopted its new name after becoming independent within the Commonwealth on 30 September 1966...
, Kenya
Kenya
Kenya , officially known as the Republic of Kenya, is a country in East Africa that lies on the equator, with the Indian Ocean to its south-east...
, Lesotho
Lesotho
Lesotho , officially the Kingdom of Lesotho, is a landlocked country and enclave, surrounded by the Republic of South Africa. It is just over in size with a population of approximately 2,067,000. Its capital and largest city is Maseru. Lesotho is a member of the Commonwealth of Nations. The name...
, Malawi
Malawi
The Republic of Malawi is a landlocked country in southeast Africa that was formerly known as Nyasaland. It is bordered by Zambia to the northwest, Tanzania to the northeast, and Mozambique on the east, south and west. The country is separated from Tanzania and Mozambique by Lake Malawi. Its size...
, Mozambique
Mozambique
Mozambique, officially the Republic of Mozambique , is a country in southeastern Africa bordered by the Indian Ocean to the east, Tanzania to the north, Malawi and Zambia to the northwest, Zimbabwe to the west and Swaziland and South Africa to the southwest...
, Namibia
Namibia
Namibia, officially the Republic of Namibia , is a country in southern Africa whose western border is the Atlantic Ocean. It shares land borders with Angola and Zambia to the north, Botswana to the east and South Africa to the south and east. It gained independence from South Africa on 21 March...
, Rwanda
Rwanda
Rwanda or , officially the Republic of Rwanda , is a country in central and eastern Africa with a population of approximately 11.4 million . Rwanda is located a few degrees south of the Equator, and is bordered by Uganda, Tanzania, Burundi and the Democratic Republic of the Congo...
, South Africa
South Africa
The Republic of South Africa is a country in southern Africa. Located at the southern tip of Africa, it is divided into nine provinces, with of coastline on the Atlantic and Indian oceans...
, Swaziland
Swaziland
Swaziland, officially the Kingdom of Swaziland , and sometimes called Ngwane or Swatini, is a landlocked country in Southern Africa, bordered to the north, south and west by South Africa, and to the east by Mozambique...
, Uganda
Uganda
Uganda , officially the Republic of Uganda, is a landlocked country in East Africa. Uganda is also known as the "Pearl of Africa". It is bordered on the east by Kenya, on the north by South Sudan, on the west by the Democratic Republic of the Congo, on the southwest by Rwanda, and on the south by...
, Tanzania
Tanzania
The United Republic of Tanzania is a country in East Africa bordered by Kenya and Uganda to the north, Rwanda, Burundi, and the Democratic Republic of the Congo to the west, and Zambia, Malawi, and Mozambique to the south. The country's eastern borders lie on the Indian Ocean.Tanzania is a state...
, Zambia
Zambia
Zambia , officially the Republic of Zambia, is a landlocked country in Southern Africa. The neighbouring countries are the Democratic Republic of the Congo to the north, Tanzania to the north-east, Malawi to the east, Mozambique, Zimbabwe, Botswana and Namibia to the south, and Angola to the west....
and Zimbabwe
Zimbabwe
Zimbabwe is a landlocked country located in the southern part of the African continent, between the Zambezi and Limpopo rivers. It is bordered by South Africa to the south, Botswana to the southwest, Zambia and a tip of Namibia to the northwest and Mozambique to the east. Zimbabwe has three...
. Kebaabetswe et al. carried out interviews in nine geographically representative locations to determine the acceptability of male circumcision as well as the preferred age and setting for male circumcision in Botswana. Their conclusion was "Male circumcision appears to be highly acceptable in Botswana. The option for safe circumcision should be made available to parents in Botswana for their male children. Circumcision might also be an acceptable option for adults and adolescents, if its efficacy as an HIV prevention strategy among sexually active people is supported by clinical trials." Boyle criticised Kebaabetswe et al.s proposal to introduce infant circumcision to Botswana saying that: "The proposal by Kebaabetswe and colleagues for the introduction of circumcision into Botswana is seriously flawed, and is irresponsible in failing to place the emphasis on safe sex practices. As described here, there are many medical, sexual, psychological, social, human rights, ethical, and legal aspects that must be considered. Reliance on circumcision to prevent HIV transmission is wishful fantasy, and can only result in a calamitous worsening of the HIV-AIDS epidemic."
Bailey et al. looked at the possible adverse effects of introducing male circumcision on a public health scale and the post operative satisfaction levels of 380 circumcisions on 18-24 year old consenting men. As to satisfaction; "At 30 days post-surgery, 99.3% of men reported being very satisfied and 0.7% somewhat satisfied with circumcision. None were dissatisfied." And with regard to adverse effects; "All were mild or moderate and resolved within hours or several days of detection." Their findings were presented at the 15th International AIDS Conference
XV International AIDS Conference, 2004
The XV International AIDS Conference was held in Bangkok, the capital city of Thailand, from July 11 to July 16, 2004. The main venue for the conference was the IMPACT Muang Thong Thani convention centre at Nonthaburi, north-east of downtown Bangkok. It was the first international AIDS conference...
held in Bangkok in 2004.
At the 15th International AIDS Conference in 2004, Connolly et al. presented their report detailing the effects of circumcision in South Africa. They reported that, among racial groups, "circumcised Blacks showed similar rates of HIV as uncircumcised Blacks, (OR: 0.8, p = 0.4) however other racial groups showed a strong protective effect, (OR: 0.3, p = 0.01)." They added "When the data are further stratified by age of circumcision, there is a slight protective effect between early circumcision and HIV among Blacks, OR: 0.7, p = 0.4." They conclude that "in general, circumcision offers slight protection." At the same conference, Thomas et al. (2004) reported that "male circumcision is not associated with HIV or STI prevention in a U.S. Navy population."
Reynolds et al. (2004) found that male circumcision was strongly protective against HIV-1 infection with circumcised men being almost seven times less at risk of HIV infection than uncircumcised men. They further state that: "The specificity of this relation suggests a biological rather than behavioural explanation for the protective effect of male circumcision against HIV-1."
Baeten et al. (2005) found that uncircumcised men were at a greater than twofold increased risk of acquiring HIV per sex act when compared with circumcised men. They conclude as follows:
- "Moreover, our results strengthen the substantial body of evidence suggesting that variation in the prevalence of male circumcision may be a principal contributor to the spread of HIV-1 in Africa."
At the 2006 Conference on Retroviruses and Opportunistic Infections Quinn et al. presented their study, conducted in Rakai
Rakai
Rakai is a town in Central Uganda. It is the headquarters of Rakai District. The district is named after the town.-Location:Rakai is located approximately , by road, southwest of Masaka, the largest town in the sub-region. This location is approximately , by road, southwest of Kampala, Uganda's...
, Uganda
Uganda
Uganda , officially the Republic of Uganda, is a landlocked country in East Africa. Uganda is also known as the "Pearl of Africa". It is bordered on the east by Kenya, on the north by South Sudan, on the west by the Democratic Republic of the Congo, on the southwest by Rwanda, and on the south by...
, which observed a 30% reduction in male-to-female HIV transmission, suggesting some protective effect for the female partner.
Newell and Bärnighausen (2007) also stated there was "firm evidence that the risk of acquiring HIV is halved by male circumcision."
Mishra et al. (2006) used data collected from the Demographic and Health Surveys
Demographic and Health Surveys
The MEASURE Demographic and Health Surveys Project is responsible for collecting and disseminating accurate, nationally representative data on health and population in developing countries. The project is implemented by Macro International, Inc...
and found that HIV prevalence was "considerably higher in urban areas and for women, especially at younger ages. Adults in wealthier households, in polygamous unions, being widowed/divorced/separated, having multiple sex partners, and having reported STIs had higher HIV rates than other adults. No consistent relationship between male circumcision and HIV risk was observed in most countries."
Way et al. (2006) also used data from Demographic and Health Surveys in Burkina Faso
Burkina Faso
Burkina Faso – also known by its short-form name Burkina – is a landlocked country in west Africa. It is surrounded by six countries: Mali to the north, Niger to the east, Benin to the southeast, Togo and Ghana to the south, and Côte d'Ivoire to the southwest.Its size is with an estimated...
, Cameroon
Cameroon
Cameroon, officially the Republic of Cameroon , is a country in west Central Africa. It is bordered by Nigeria to the west; Chad to the northeast; the Central African Republic to the east; and Equatorial Guinea, Gabon, and the Republic of the Congo to the south. Cameroon's coastline lies on the...
, Ghana
Ghana
Ghana , officially the Republic of Ghana, is a country located in West Africa. It is bordered by Côte d'Ivoire to the west, Burkina Faso to the north, Togo to the east, and the Gulf of Guinea to the south...
, Kenya
Kenya
Kenya , officially known as the Republic of Kenya, is a country in East Africa that lies on the equator, with the Indian Ocean to its south-east...
, Lesotho
Lesotho
Lesotho , officially the Kingdom of Lesotho, is a landlocked country and enclave, surrounded by the Republic of South Africa. It is just over in size with a population of approximately 2,067,000. Its capital and largest city is Maseru. Lesotho is a member of the Commonwealth of Nations. The name...
, and Malawi
Malawi
The Republic of Malawi is a landlocked country in southeast Africa that was formerly known as Nyasaland. It is bordered by Zambia to the northwest, Tanzania to the northeast, and Mozambique on the east, south and west. The country is separated from Tanzania and Mozambique by Lake Malawi. Its size...
and from AIDS Indicator Surveys in Tanzania
Tanzania
The United Republic of Tanzania is a country in East Africa bordered by Kenya and Uganda to the north, Rwanda, Burundi, and the Democratic Republic of the Congo to the west, and Zambia, Malawi, and Mozambique to the south. The country's eastern borders lie on the Indian Ocean.Tanzania is a state...
and Uganda
Uganda
Uganda , officially the Republic of Uganda, is a landlocked country in East Africa. Uganda is also known as the "Pearl of Africa". It is bordered on the east by Kenya, on the north by South Sudan, on the west by the Democratic Republic of the Congo, on the southwest by Rwanda, and on the south by...
to conduct his study. They found that "With age, education, wealth status, and a number of sexual and other behavioral risk factors controlled statistically, in only one of the eight countries were circumcised men at a significant advantage. In the other seven countries, the association between circumcision and HIV status was not statistically significant for the male population as a whole."
Garenne (2006) has doubts about circumcision's value in reducing HIV, and Talbott (2007), in a controversial paper stated that cross country regression data pointed to prostitution as the key factor in the AIDS epidemic rather than circumcision. World Health Organization AIDS Prevention Team official Tim Farley disagreed with the findings of the paper, while Chris Surridge, PLoS One's managing editor, defended its publication. In 1999 the American Medical Association had stated, "behavioral factors are far more important in preventing these infections than the presence or absence of a foreskin."
If proper hygienic procedures are not adhered to, the circumcision operation itself can spread HIV. Brewer et al. (2007) report, "[circumcised] male and female virgins were substantially more likely to be HIV infected than uncircumcised virgins. Among adolescents, regardless of sexual experience, circumcision was just as strongly associated with prevalent HIV infection. However, uncircumcised adults were more likely to be HIV positive than circumcised adults." They concluded: "HIV transmission may occur through circumcision-related blood exposures in eastern and southern Africa."
Van Howe et al. criticise the drive to promote circumcision in Africa, asking "Why are circumcision proponents expending so much time and energy promoting mass circumcision to North Americans when their supposed aim is to prevent HIV in Africa? The circumcision rate is declining in the US, especially on the west coast; the two North American national paediatric organisations have elected not to endorse the practice, and the practice’s legality has been questioned in both the medical and legal literature. ‘Playing the HIV card’ misdirects the fear understandably generated in North Americans by the HIV/AIDS pandemic into a concrete action: the perpetuation of the outdated practice of neonatal circumcision."
Connolly et al. (2008) found that "circumcision had no protective effect in the prevention of HIV transmission. This is a concern, and has implications for the possible adoption of the mass male circumcision strategy both as a public health policy and an HIV prevention strategy."
Sidler et al. (2008) say that using neonatal non-therapeutic circumcision to combat the HIV crisis in Africa is neither medically nor ethically justifiable. Furthermore, promoting circumcision might worsen the problem by creating a false sense of security and therefore undermining safe sex practices. Education, female economic independence, safe sex practices and consistent condom use are proven effective measures against HIV transmission.
Boiley et al. (2008) found that the protection of circumcision against STI contributes little to the overall effect of circumcision on HIV.
Men who have sex with men (MSM)
Millett et al. (2007) found no association in three major US cities between circumcision and HIV infection among Latino and black men who have sex with men (MSM) . They conclude as follows: "In these cross-sectional data, there was no evidence that being circumcised was protective against HIV infection among black MSM or Latino MSM."Lagarde (2003) stated that "More than 70% of the non-circumcised men (NCM) stated that they would want to be circumcised if MC were proved to protect against sexually transmitted diseases (STD)." Lagarde cautioned that "Our results strongly suggest that interventions including MC should carefully address the false sense of security that it may provide."
A 2008 meta-analysis of 15 observational studies, including 53,567 gay and bisexual men from the United States, Britain, Canada, Australia, India, Taiwan, Peru and the Netherlands (52% circumcised), found that the rate of HIV infection was non-significantly lower among men who were circumcised compared with those who were uncircumcised. For men who engaged primarily in insertive anal sex, a protective effect was observed, but it too was not statistically significant. Observational studies included in the meta-analysis that were conducted prior to the introduction of highly active antiretroviral therapy in 1996 demonstrated a statistically significant protective effect for circumcised MSM against HIV infection. In response to the meta-analysis by Millett et al., Vermund and Qian note that "circumcision would likely be insufficiently efficient to be universally effective in reducing HIV risk, and will have to be combined with other prevention modalities to have a substantial and sustained prevention effect."
Randomised controlled trials
AfricaAfrica
Africa is the world's second largest and second most populous continent, after Asia. At about 30.2 million km² including adjacent islands, it covers 6% of the Earth's total surface area and 20.4% of the total land area...
has a higher rate of adult HIV infection than anywhere else in the world. Three randomised controlled trials
Randomized controlled trial
A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...
were commissioned in Africa to investigate whether circumcision could lower the rate of HIV contraction.
The first study to be published was named ANRS-1265. It was funded by the French government’s research agency, Agence Nationale de Recherches sur la SIDA (ANRS) and carried out in Orange Farm, Gauteng
Orange Farm, Gauteng
Orange Farm is a township located approximately 45 km from Johannesburg, Gauteng Province, South Africa. It is the largest informal settlement in South Africa, with most estimates giving a population of 1 million people. Additionally, it is one of the youngest, with the original inhabitants;...
in South Africa
South Africa
The Republic of South Africa is a country in southern Africa. Located at the southern tip of Africa, it is divided into nine provinces, with of coastline on the Atlantic and Indian oceans...
. The purpose was to test the effect of adult male circumcision on HIV acquisition.
The principal investigator was Dr. Bertran Auvert of Versailles University. The study enrolled 3,274 men aged 18–24. The participants were split into two equal groups. One group was circumcised straight away; the other group, serving as a control, was to be circumcised 21 months later. 146 of the original participants were found to have HIV at the start of the trial - to avoid stigmatization, they were not excluded. It was planned that all the men would visit the research clinic four times during this 21-month period, and that they would be tested for HIV each time. They were instructed not to have sex for six weeks after the operation, and asked at each clinic visit to provide detailed information about their sexual activity. The circumcision procedure used was the forceps-guided method http://www.phru.co.za/pdf/circumcision/pitfalls.pdf, carried out by three local general practitioners in their surgical offices. After 17 months, 20 men had contracted HIV in the circumcised group and 49 in the control group. The trial was halted on ethical grounds. The results of the trial were published in November 2005.
The authors said, “Male circumcision provides a degree of protection against acquiring HIV infection, equivalent to what a vaccine of high efficacy would have achieved. Male circumcision may provide an important way of reducing the spread of HIV infection in sub-Saharan Africa.”
Williams et al.(2006) looked at the potential impact of circumcision on HIV in Africa, based upon the South African RCT, saying that that male circumcision (MC) could substantially reduce the burden of HIV in Africa, particularly in southern Africa where the existing prevalence of male circumcision is low and the existing prevalence of HIV is high. More specifically it predicted that if full coverage with MC was achieved in sub-Saharan Africa over the next ten years, MC could prevent approximately 2.0 (1.1 to 3.8) million new HIV infections over that ten year period and a further 3.7 million in the ten years after that.
The above conclusions drawn from the Orange Farm study have been criticised by Michel Garenne (2006) of the Institut Pasteur. In his critique, published on the PLoS Journal of Medicine, he concludes that: "'male circumcision should be regarded as an important public health intervention for preventing the spread of HIV' appears overstated. Even though large-scale male circumcision could avert a number of HIV infections, theoretical calculations and empirical evidence show that it is unlikely to have a major public health impact, apart from the fact that achieving universal male circumcision is likely to be more difficult than universal vaccination coverage or universal contraceptive use."
Mills and Siegfried (2006) point out that trials that are stopped early tend to over estimate treatment effects.
They argued that a meta-analysis should be done before further feasibility studies are done.
The NIAID
National Institute of Allergy and Infectious Diseases
The National Institute of Allergy and Infectious Diseases is one of the 27 institutes and centers that make up the National Institutes of Health , an agency of the United States Department of Health and Human Services...
, part of the NIH
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
, supported two further trials, conducted in Kenya and in Uganda. The primary objectives of these studies were to determine whether adult male circumcision can be administered safely, and whether it would reduce the risk of acquiring HIV infection through heterosexual contact. After an initial HIV screening and a medical exam, eligible men were randomly assigned either to receive circumcision immediately or to wait two years before circumcision. All participants were closely followed for two years to collect information about their health, sexual activity, and their and their partners’ attitudes about circumcision; to counsel participants in HIV prevention and safe sex practices; and to check the HIV status of the volunteer. Participants in the Kenyan study were scheduled for six visits over the two-year follow-up, compared with four visits for the Ugandan trial participants. In addition to the study visits, men enrolled in the Kenyan trial were encouraged to receive all of their outpatient health care at the study clinics, which enabled researchers to collect information on the safety of the procedure and the number of other sexually transmitted diseases the men had during follow-up.
The Kenyan trial, also known as the UNIM trial (Universities of Nairobi, Illinois and Manitoba trial), began in February 2002, in Kisumu
Kisumu
Kisumu is a port city in western Kenya at , with a population of 355,024 . It is the third largest city in Kenya, the principal city of western Kenya, the immediate former capital of Nyanza Province and the headquarters of Kisumu County. It has a municipal charter but no city charter...
, Kenya
Kenya
Kenya , officially known as the Republic of Kenya, is a country in East Africa that lies on the equator, with the Indian Ocean to its south-east...
. It was a collaborative effort between US, Canadian and Kenyan researchers, led by Dr. Robert Bailey, of the University of Illinois. Also involved were Stephen Moses, University of Manitoba
University of Manitoba
The University of Manitoba , in Winnipeg, Manitoba, Canada, is the largest university in the province of Manitoba. It is Manitoba's most comprehensive and only research-intensive post-secondary educational institution. It was founded in 1877, making it Western Canada’s first university. It placed...
, Jeckoniah Ndinya-Achola, University of Nairobi
University of Nairobi
The University of Nairobi is the largest university in Kenya. Although its history as an educational institution goes back to 1956, it did not become an independent university until 1970 when the University of East Africa was split into three independent universities: Makerere University in...
, and Kwango Agot, UNIM. The trial was funded by the NIAID and the Canadian Institutes of Health Research
Canadian Institutes of Health Research
Canadian Institutes of Health Research is the major federal agency responsible for funding health research in Canada. It is the successor to the Medical Research Council of Canada. It aims to create new health knowledge, and to translate that knowledge from the research setting into real world...
. This trial enrolled 2,784 men between 18 and 24 years old. The participants were assessed by HIV testing, medical examinations, and behavioural interviews during follow-ups at 1, 3, 6, 12, 18, and 24 months. The circumcision procedure used in the Ugandan trial is known as the sleeve method and takes about 30 minutes. The Ugandan trial used cauterization of the blood vessels to control bleeding and stitches to close the wound. 22 men in the intervention group and 47 in the control group had tested positive for HIV when the study was stopped on ethical grounds.
The Ugandan trial began August, 2003 in Rakai
Rakai District
Rakai District is a district in Central Uganda. Like most other Ugandan districts, it is named after its 'chief town', Rakai.-Location:Rakai District borders Lyantonde District to the northwest, Lwengo District to the north, Masaka District to the northeast, Kalangala District to the east, the...
, Uganda
Uganda
Uganda , officially the Republic of Uganda, is a landlocked country in East Africa. Uganda is also known as the "Pearl of Africa". It is bordered on the east by Kenya, on the north by South Sudan, on the west by the Democratic Republic of the Congo, on the southwest by Rwanda, and on the south by...
, with 4,996 men aged between 15 and 49 years old. It was led by Ronald Gray and Maria Wawer of Johns Hopkins Bloomberg School of Public Health
Johns Hopkins Bloomberg School of Public Health
The Johns Hopkins Bloomberg School of Public Health is part of Johns Hopkins University in Baltimore, Maryland, United States...
and David Serwadda and Nelson Sewankambo of Makerere University
Makerere University
Makerere University , Uganda's largest and second-oldest higher institution of learning, , was first established as a technical school in 1922. In 1963 it became the University of East Africa, offering courses leading to general degrees from the University of London...
in Kampala
Kampala
Kampala is the largest city and capital of Uganda. The city is divided into five boroughs that oversee local planning: Kampala Central Division, Kawempe Division, Makindye Division, Nakawa Division and Lubaga Division. The city is coterminous with Kampala District.-History: of Buganda, had chosen...
, Uganda. The circumcision procedure used in the Kenyan trial was the foreskin clamp method. The Kenyan trial procedure took about 25 minutes and used stitches to control bleeding and improve wound closure. Trained and certified physicians performed the circumcisions in well-equipped operating rooms. Post-operative follow-up visits were scheduled at 24–48 hours, 5–9 days, and 4–6 weeks. HIV testing, physical examination, and interviews were repeated at 4–6 weeks, 6-, 12-, and 24-month follow-up visits. After 24 months, 964 of the original 2387 men of the circumcised men had been retained of whom 22 had contracted HIV. 980 of the 2430 uncircumcised men had been retained of whom 45 had contracted HIV.
Both trials were stopped early on December 13, 2006 on ethical grounds after it found that those belonging to the control group had a greater number of men with HIV than the circumcised group.
On Wednesday, March 28, 2007, the World Health Organisation (WHO) and UNAIDS issued joint recommendations concerning male circumcision and HIV/AIDS. These recommendations are:
- Male circumcision should now be recognized as an efficacious intervention for HIV prevention.
- Promoting male circumcision should be recognized as an additional, important strategy for the prevention of heterosexually acquired HIV infection in men.
Kim Dickson, coordinator of the working group that authored the report, commented:
- Male circumcision "would have greatest impact" in countries where the HIV infection rate among heterosexual males is greater than 15 percent and fewer than 20 percent of males are circumcised.
- WHO further recommends that the procedure must be done by a trained physician.
- Protection is incomplete and men must continue to use condoms and have fewer partners.
- Newly circumcised men should abstain from sex for at least six weeks.
The World Health Organization (WHO) said: “Although these results demonstrate that male circumcision reduces the risk of men becoming infected with HIV, the UN agencies emphasize that it does not provide complete protection against HIV infection. Circumcised men can still become infected with the virus and, if HIV-positive, can infect their sexual partners. Male circumcision should never replace other known effective prevention methods and should always be considered as part of a comprehensive prevention package, which includes correct and consistent use of male or female condoms, reduction in the number of sexual partners, delaying the onset of sexual relations, and HIV testing and counselling.”
Others have also expressed concern that some may mistakenly believe they will be fully protected against HIV through circumcision and see circumcision as a safe alternative to other forms of protection, such as condoms.
Dowsett et al. urged caution over using circumcision as a HIV prevention strategy saying that there were still questions that needed to be answered: "We need to investigate the effects of those other social and contextual factors that will be in play in real world settings – because the effectiveness of male circumcision will not be generated by the efficacy of the surgery alone." He contrasts the preventative effect of circumcision taken from the RCT's (55%) with the preventative effect of condoms (80-90%). He criticises the fact that the trials were not double-blinded - the participants knew their circumcision status and so this could have affected how the men responded behaviourally, psychologically and sexually. He criticised the randomisation measures used in the trial: sexual practices (number of partners, condom use) and sexual health measures (presence of STIs), saying that "Effective measures were not used, and differences related to sexual subjectivity, such as sexual network participation, pleasure preferences, body image, sexual history effects (e.g. abuse), partner preferences (younger, older, peers, groups) and so on were never assessed or analysed." He also asks how the extensive counselling and education might have influenced the participants' sexual activity. He adds that "all participants were subject to
regular monitoring (e.g. behaviour surveys, clinical check-ups), which clearly might have enhanced compliance with suggested safety regimes and lowered risk-taking during the follow-up period. Such compliance cannot be
guaranteed in real world settings." He also said the trials were subject to the Hawthorne effect
Hawthorne effect
The Hawthorne effect is a form of reactivity whereby subjects improve or modify an aspect of their behavior being experimentally measured simply in response to the fact that they know they are being studied, not in response to any particular experimental manipulation.The term was coined in 1950 by...
.
An interim analysis from the Rakai Health Sciences Program in Uganda suggested that newly circumcised HIV positive men may be more likely to spread HIV to their female partners if they have sexual intercourse before the wound is fully healed. “Because the total number of men who resumed sex before certified wound healing is so small, the finding of increased transmission after surgery may have occurred by chance alone. However, we need to err on the side of caution to protect women in the context of any future male circumcision programme,” said Maria Wawer, the study's principal investigator.
Kalichman et al. (2007) argue that any protective effects circumcision could offer would be partially offset by increased HIV risk behavior, or “risk compensation" including reduction in condom use or increased numbers of sex partners. They note that circumcised men in the South African trial had 18% more sexual contacts than uncircumcised men at follow-up. They also said that because participants were given ongoing risk-reduction counseling and free condoms, it "reduced the utility of these trials for estimating the potential behavioral impact of male circumcision when implemented in a natural setting." They also criticised current models for failing to account for increased HIV risk behaviour. Increased HIV risk behaviour would mean more women would be infected which would consequently increase the risk of men. It would also mean that non-HIV STI's, which have been associated with increased HIV risk, would increase. Green et al. (2008) also disagree with using circumcision to prevent HIV, citing similar reasons.
Published meta-analyses, using data from the RCTs, have estimated the summary relative risk
Relative risk
In statistics and mathematical epidemiology, relative risk is the risk of an event relative to exposure. Relative risk is a ratio of the probability of the event occurring in the exposed group versus a non-exposed group....
at 0.42 (95% CI
Confidence interval
In statistics, a confidence interval is a particular kind of interval estimate of a population parameter and is used to indicate the reliability of an estimate. It is an observed interval , in principle different from sample to sample, that frequently includes the parameter of interest, if the...
0.31-0.57), 0.44 (0.33-0.60) and 0.43 (0.32-0.59). (rate of HIV infection in circumcised divided by rate in uncircumcised men). Weiss et al. report that meta-analysis of "as-treated" figures from RCTs reveals a stronger protective effect (0.35; 95% CI 0.24-0.54) than if "intention-to-treat" figures are used. Byakika-Tusiime also estimated a summary relative risk of 0.39 (0.27-0.56) for observational studies, and 0.42 (0.33-0.53) overall (including both observational and RCT data). Weiss et al. report that the estimated relative risk using RCT data was "identical" to that found in observational studies (0.42). Byakika-Tusiime states that available evidence satisfies six of Hill's criteria, and concludes that the results of her analysis "provide unequivocal evidence that circumcision plays a causal role in reducing the risk of HIV infection among men." Mills et al. conclude that circumcision is an "effective strategy for reducing new male HIV infections", but caution that consistently safe sexual practices will be required to maintain the protective effect at the population level. Weiss et al. conclude that the evidence from the trials is conclusive, but that challenges to implementation remain, and will need to be faced.
Estimated impact of circumcision programs
Modelling of the population-level impact of circumcision has shown mixed results. Podder et al. found that although circumcision would not eliminate HIV, it would "significantly reduce" the HIV burden in a population, stating that reduction was more effective when circumcision was combined with anti-retroviral drugs than with condomCondom
A condom is a barrier device most commonly used during sexual intercourse to reduce the probability of pregnancy and spreading sexually transmitted diseases . It is put on a man's erect penis and physically blocks ejaculated semen from entering the body of a sexual partner...
s. Disease elimination was considered feasible when all interventions were combined. Hallet et al. predicted "dramatic" reductions in HIV if circumcision were scaled up alongside behaviour change programmes.
Studies of the cost-effectiveness of circumcision programmes have been similarly mixed. Kahn et al. studied sub-Saharan African settings with a high or moderate HIV prevalence, reporting that adult circumcision is "likely to be a cost-effective HIV prevention strategy" even when deployed among only a small fraction of the population. The authors concluded that circumcision "generates large net savings after adjustment for averted HIV medical costs". White et al. concluded that circumcision "is a cost-saving intervention in a wide range of scenarios of HIV and initial circumcision prevalence but the United Nations Joint Programme on HIV/AIDS/WHO recommended target age group should be widened to include older HIV-uninfected men and counselling should be targeted at both newly and already circumcised men to minimize risk compensation". The UNAIDS/WHO/SACEMA Expert Group on Modelling the Impact and Cost of Male Circumcision for HIV Prevention found "large benefits" of circumcision in settings with high HIV prevalence and low circumcision prevalence. The Group estimated "one HIV infection being averted for every five to 15 male circumcisions performed, and costs to avert one HIV infection ranging from US$150 to US$900 using a 10-y time horizon". McAllister et al. estimated that consistent condom use is 95 times more cost effective than circumcision at reducing the rate of HIV in sub-Saharan Africa; the World Health Organisation states that circumcision is "highly cost-effective" in comparison to other HIV interventions when data from the South African trial are used, but less cost-effective when data from the Ugandan trial are used.
Langerhans cells and HIV transmission
Langerhans cells are part of the human immune system. Three studies identified high concentrations of Langerhans and other "HIV target" cells in the foreskin and Szabo and Short suggested that the Langerhans cells in the foreskin may provide an entry point for viral infection. McCoombe, Cameron, and Short also found that the keratin is thinnest on the foreskin and frenulum. Van Howe, Cold and Storms criticised Szabo and Short's suggestion as "pure speculation". Fleiss, Hodges and Van Howe had previously stated a belief that the prepuce has an immunological function. Waskett criticised their specific hypothesis on technical grounds. A study published in 2007 by de Witte and others said that langerinLangerin
CD207, langerin is a protein which in humans is encoded by the CD207 gene. Langerin is a type II transmembrane cell surface receptor produced by Langerhans cells.-Function:...
, produced by Langerhans cells, is a natural barrier to HIV-1 transmission by Langerhans cells.
Dowsett (2007) questioned why it was just males that were being encouraged to circumcise: "Langerhans cells occur in the clitoris
Clitoris
The clitoris is a sexual organ that is present only in female mammals. In humans, the visible button-like portion is located near the anterior junction of the labia minora, above the opening of the urethra and vagina. Unlike the penis, which is homologous to the clitoris, the clitoris does not...
, the labia and in other parts of both male and female genitals, and no one is talking of removing these in the name of HIV prevention."