Circumcision lowers the risk of HIV/AIDS infection



Summaries of Research Results


Circumcision and its effects in Africa

Taiwo Akeem Lawa and E. Oluwabunmi Olapade-Olaopa, Transl Androl Urol. 2017 Apr; 6(2): 149–157.


Abstract
Male circumcision is one of the most commonly performed procedures in Africa, with a wide variation between the different regions on the practice. This is because circumcision is often done for religious and cultural or traditional reasons, which includes being part of rituals or rite of passage to adulthood. There had been few medical indications for the procedure until the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) pandemic, which is prevalent in many of the countries in the region. Evidence from randomized controlled trials conducted in the continent had shown that male circumcision could be instrumental to reducing the transmission of HIV/AIDS in heterosexual couples in high disease prevalent and low circumcision prevalent areas. This had led to the roll-out of large population-based adult male circumcisions as well as the development of tools to facilitate the procedure. Circumcision, however, is not without complications and the incidence appears related to the age of the patient, where the procedure was done, technique used and level of proficiency of the practitioners. This article reviews the practice of circumcision in Africa and highlights the impact of the procedure on the continent.

Conclusions
Male circumcision in Africa is a procedure that has been proven to be of public health significance in the reduction of the scourge of HIV infection while also leading to reduction in prevalence of some other STIs but is practiced in a variety of ways that may be associated with adverse effects of unacceptable magnitude. In order to achieve the set targets of the VMMC programs rolled out across sub-Saharan Africa, there is a need to strengthen existing services for surgical circumcision, broaden the available network of trained healthcare providers to perform the procedure and train them on the use of devices that have been found to be safe and associated with minimal adverse effects.
For the full online article, see here.


Why Circumcision reduces the risk of HIV infection

Circumcision study supports HIV theory. Researchers say the foreskin can shelter troublesome bacteria, so its removal may bolster the immune system to keep the AIDS virus at bay.
April 15, 2013, By Monte Morin, Los Angeles Times

Circumcision is known to reduce a man's risk of HIV infection by at least half, but scientists don't know why. A new study offers support for the theory that removing the foreskin deprives troublesome bacteria of a place to live, leaving the immune system in much better shape to keep the human immunodeficiency virus at bay. Anyone who has ever lifted a rock and watched as the earth beneath it was quickly vacated by legions of bugs and tiny worms would be familiar with the principle, said study leader Dr. Cindy Liu: After the foreskin is cut away, the masses of genital bacteria that once existed beneath it end up disappearing. "It's the same as if you clear-cut a forest," said Liu, a pathologist at the Translational Genomics Research Institute in Flagstaff, Ariz. "The community of animals that once lived in that forest is going to change." Of particular note is that circumcision undercuts anaerobic bacteria, the microbes that thrive in oxygen-deprived environments, she said. By reducing the number of anaerobic bacteria, the body's immune cells may be better able to destroy the virus — and less likely to fall prey to its Trojan horse-style of attack, the authors suggest.

Liu and her colleagues present their case in a paper published Tuesday in the journal mBio. Numerous studies conducted over the last two decades have shown that male circumcision reduces the risk of HIV infection in men who have heterosexual intercourse by 50% to 60%. Some researchers have speculated that the foreskin is prone to tearing, giving the virus more routes of entry. Others have argued that removal of the foreskin simply reduces the surface area available to be infected. Liu and coauthor Lance Price, a professor of environmental health sciences at George Washington University in Washington, suspected it had to do with the bacterial species that inhabit the coronal sulcus, the shallow groove behind the head, or glans, of the penis. To establish a possible connection, study authors enrolled 156 Ugandan men in a randomized trial in which half of them were circumcised and the other half were not. Study participants ranged in age from 15 to 49. While the prospect of undergoing circumcision as an adult might not appeal to many American men, 5,000 Ugandan males volunteered for the study. In a region where 1 in 6 people are infected with HIV, circumcision's "powerful potential" to reduce the risk of infection was strong motivation, said coauthor Dr. Aaron Tobian, a health epidemiologist and pathologist who teaches at Johns Hopkins University School of Medicine. On average, there was an 81% reduction in bacteria in the circumcised men one year after surgery, the researchers reported. Some of the biggest drops were recorded for anaerobic bacteria, they said. Bacteria on the coronal sulcus fell by more than 33% in the circumcised men, Liu said. Interestingly, the men in the uncircumcised control group also experienced a reduction in bacteria, but not to the degree that the circumcised men did, Liu said. This was probably because of health and hygiene information that was given to all study participants. "That's not an uncommon outcome," she said. "Just being in a trial can confer some benefits." The study only examined the effect of circumcision on reducing or altering bacterial colonies on the penis. Further research must be done to draw a direct connection between these changes in the icrobiome and subsequent HIV infection. However, the study offers strong support for the idea that bacteria — particularly anaerobic bacteria — can cause inflammation that will trigger the body's immune system and summon a variety of cells to fight a threat. Among those fighters are T4 cells, which are infected by HIV. The virus needs those cells to survive and replicate over time. The study authors argue that the large populations of bacteria in uncircumcised men attract these T4 cells, giving the virus a means of entry during intercourse with an infected person. However, circumcised men are much less likely to mobilize these susceptible cells; therefore, the virus can be destroyed by other types of immune cells.


Chicago Researchers find why uncircumcised men have more HIV

A new study conducted by Chicago researchers shows that internal mucosal layers of foreskin are more susceptible to HIV infection than cervical tissue or the external layers of foreskin, which explains why uncircumcised men seem to be at much higher risk for HIV acquisition than men who are circumcised.

Previously, numerous studies reported that uncircumcised men have higher rates of HIV infection and are at a twofold to eightfold increased risk of becoming infected with HIV compared to circumcised men. However, why circumcision plays a protective role against acquisition of HIV has been unknown.

A study published in the September issue of the American Journal of Pathology by researchers at Rush-Presbyterian-St. Luke’s Medical Center, Children’s Memorial Hospital and the University of Illinois at Chicago School of Public Health points to the biological mechanisms underlying this protective effect.

The researchers examined foreskin tissue obtained from eight children and six adults who were undergoing circumcision for other reasons. Those tissues were compared with cervical tissue, which served as controls. The analysis showed that foreskin mucosa (cells underneath the surface) contain high concentrations of the cells targeted by HIV. The foreskin tissue contained higher densities of CD4+ T cells, macropahges and Langerhans’ Cells (LC) in adults than in children or in cervical tissue. The highest proportion of these HIV target cells were found in men with a history of infection, which is consistent with studies finding that men with sexually transmitted infections are more susceptible to HIV.

According to Alan Landay, PhD, department of Immunology/Microbiology and at Rush-Presbyterian-St. Luke’s Medical Center, the higher the concentration of HIV target cells, the more susceptible the tissue is to HIV. This proved to be the case. When the authors introduced HIV to the tissue in culture, the cells in the foreskin tissues were infiltrated with HIV rapidly and at much greater intensity than the cervical tissue.

According to the first author, Bruce Patterson, M.D, viral pathologist in the division of Infectious Diseases at Children’s Memorial Hospital, there are logical, but as yet unproven theories explaining how HIV infection occurs in the circumcised penis. "Infection may occur through the urethral mucosa or through disruptions of the penile shaft epithelia caused by genital ulcer disease or trauma," he said. In uncircumcised men, Patterson said that the thin keratin layer they found on the inner compared to the outer mucosal surface predisposed the foreskin to infection.

The authors mention that a limitation of the study is that they were unable to obtain tissue from circumcised penises for comparison.

However, the study’s senior author, Robert Bailey, PhD, MPH, from the Division of Epidemiology, School of Public Health at the University of Illinois at Chicago, is conducting a study in east Africa that will address this issue. Bailey and his collaborators have begun a randomized controlled trial to compare HIV acquisition in 1,400 African males age 18-24 who will be circumcised with 1,400 in the same city who are not circumcised. Bailey’s team will take two years to recruit all the young men and will follow each group for two years, providing them with HIV prevention counseling and free medical treatment. After four years of study, they will be able to determine if circumcision reduced the men’s chances of becoming HIV infected.

Landay said that the implications of this foreskin tissue evaluation and the positive association between uncircumcisized individuals and HIV acquisition indicate that strong consideration should be given to integrating male circumcision information and services with other HIV preventive methods.


Male circumcision protects against HIV infection

Uncircumcised men are at a much greater risk of becoming infected with HIV than circumcised men, according to new evidence in published in the British Medical Journal in June 2000.

Using information from over 40 previous studies, researchers in Australia suggest that the virus targets specific cells found on the inner surface of the foreskin. These cells possess HIV receptors, making this area particularly susceptible to infection. The researchers propose that male circumcision provides significant protection against HIV infection by removing most of the receptors.

The most dramatic evidence of this protective effect comes from a new study of couples in Uganda, where each woman was HIV positive and her male partner was not. Over a period of 30 months, no new infections occurred among 50 circumcised men, whereas 40 of 137 uncircumcised men became infected - even though all couples were given advice about preventing infection and free condoms were available to them.

Although cultural and religious attitudes towards male circumcision are deeply divided, the authors conclude that, in the light of the evidence, male circumcision should be seriously considered as an additional means of preventing HIV in countries with a high level of infection. Alternatively, say the authors, the development of 'chemical condoms' ' products which can block HIV receptors in the penis and the vagina ' might provide a more acceptable form of HIV prevention in the future.


Making voluntary medical male circumcision a viable HIV prevention strategy in high-prevalence countries by engaging the traditional sector

Nicola Bulleda & Edward C. Green The Center for Global Health, University of Virginia, Charlottesville, VA, USA; Johns Hopkins University, Baltimore, MD, USA

Voluntary medical male circumcision (VMMC) has been rapidly accepted by global HIV policy and donor institutions as a highly valuable HIV prevention strategy given its cost-effectiveness, limited interactions with a health facility and projected long-lasting benefits. Many southern African countries have incorporated VMMC into their national HIV prevention strategies. However, intensive VMMC promotion programs have met with limited success to date and many HIV researchers have voiced concerns. This commentary discusses reasons behind the less-than-desired public demand and suggests how inclusion of the traditional sector - traditional leaders, healers, and circumcisers - with their local knowledge, cultural expertise and social capital, particularly in the realm of social meanings ascribed to male circumcision (MC), may improve the uptake of this HIV prevention strategy. We offer Lesotho and Swaziland as case studies of the integration of universal VMMC policies; these are countries with a shared HIV burden, yet contrasting contemporary sociocultural practices of MC. The similar hesitant responses expressed by these two countries towards VMMC remind us that the incorporation of any new or revised and revitalized public health strategy must be considered within unique historical, political, economic, and sociocultural contexts.
For the online abstract see here.


Male Circumcision and STI acquisition in Britain: Evidence from a National Probability Sample Survey.

Homfray V, Tanton C et al., PLoS One 2015 Jun 17;10(6):e0130396. doi: 10.1371/journal.pone.0130396. eCollection 2015.

ABSTRACT:
BACKGROUND:
It is well-established that male circumcision reduces acquisition of HIV, herpes simplex virus 2, chancroid, and syphilis. However, the effect on the acquisition of non-ulcerative sexually transmitted infections (STIs) remains unclear. We examined the relationship between circumcision and biological measures of three STIs: human papillomavirus (HPV), Chlamydia trachomatis and Mycoplasma genitalium.

METHODS:
A probability sample survey of 15,162 men and women aged 16-74 years (including 4,060 men aged 16-44 years) was carried out in Britain between 2010 and 2012. Participants completed a computer-assisted personal interview, including a computer-assisted self-interview, which asked about experience of STI diagnoses, and circumcision. Additionally, 1,850 urine samples from sexually-experienced men aged 16-44 years were collected and tested for STIs. Multivariable logistic regression was used to calculate adjusted odds ratios (AOR) to quantify associations between circumcision and i) self-reporting any STI diagnosis and ii) presence of STIs in urine, in men aged 16-44 years, adjusting for key socio-demographic and sexual behavioural factors.

RESULTS:
The prevalence of circumcision in sexually-experienced men aged 16-44 years was 17.4% (95%CI 16.0-19.0). There was no association between circumcision and reporting any previous STI diagnoses, nd specifically previous chlamydia or genital warts. However, circumcised men were less likely to have any HPV type (AOR 0.26, 95% confidence interval (CI) 0.13-0.50)

CONCLUSIONS:
Circumcised men had reduced odds of HPV detection in urine. These findings have implications for improving the precision of models of STI transmission in populations with different circumcision prevalence and in designing interventions to reduce STI acquisition.
For the online abstract , see here.


Penile Microbiota and Female Partner Bacterial Vaginosis in Rakai, Uganda.

Liu CM, Hungate BA et al., MBio. 2015 Jun 16;6(3). pii: e00589-15. doi: 10.1128/mBio.00589-15.

ABSTRACT:
Bacterial vaginosis (BV) is a common vaginal bacterial imbalance associated with risk for HIV and poor gynecologic and obstetric outcomes. Male circumcision reduces BV-associated bacteria on the penis and decreases BV in female partners, but the link between penile microbiota and female partner BV is not well understood. We tested the hypothesis that having a female partner with BV increases BV-associated bacteria in uncircumcised men. We characterized penile microbiota composition and density (i.e., the quantity of bacteria per swab) by broad-coverage 16S rRNA gene-based sequencing and quantitative PCR (qPCR) in 165 uncircumcised men from Rakai, Uganda. Associations between penile community state types (CSTs) and female partner's Nugent score were assessed. We found seven distinct penile CSTs of increasing density (CST1 to 7). CST1 to 3 and CST4 to 7 were the two major CST groups. CST4 to 7 had higher prevalence and abundance of BV-associated bacteria, such as Mobiluncus and Dialister, than CST1 to 3. Men with CST4 to 7 were significantly more likely to have a female partner with a high Nugent score (P = 0.03). Men with two or more extramarital partners were significantly more likely to have CST4 to 7 than men with only marital partners (CST4 to 7 prevalence ratio, 1.84; 95% confidence interval [CI], 1.16 to 2.92). Female partner Nugent BV is significantly associated with penile microbiota. Our data support the exchange of BV-associated bacteria through intercourse, which may explain BV recurrence and persistence.

IMPORTANCE:
Bacterial vaginosis (BV) is sexually associated but not considered a sexually transmitted disease. Our findings suggest that the uncircumcised penis is an important niche for BV-associated genital anaerobes. In addition, we found a link between extramarital sexual relationships and BV-associated bacteria in men, which parallels earlier findings of the association between sexual activity and BV in women. This suggests the sexual transmissibility of BV-associated bacteria. Reducing bacterial exchange by barrier methods and managing carriage of BV-associated bacteria in men may decrease BV persistence and recurrence in women.


Circumcision Status and Risk of HIV Acquisition during Heterosexual Intercourse for Both Males and Females: A Meta-Analysis.

Lei JH, Liu LR al., PLoS One 2015 May 5;10(5):e0125436

ABSTRACT:
In this study, we evaluated if male circumcision was associated with lower HIV acquisition for HIV (-) males and HIV (-) females during normal sexual behavior. We performed a systematic literature search of PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) databases to identify studies that compared HIV acquisition for the circumcised and uncircumcised groups. The reference lists of the included and excluded studies were also screened. Fifteen studies (4 RCTs and 11 prospective cohort studies) were ncluded, and the related data were extracted and analyzed in a meta-analysis. Our study revealed strong evidence that male circumcision was associated with reduced HIV acquisition for HIV(-) males less than 0.00001] and provided a 70% protective effect. In contrast, no difference was detected in HIV acquisition for HIV (-) females between the circumcised and uncircumcised groups (pooled adjusted RR after sensitivity analysis: 0.68, 95%CI 0.40-1.15, P = 0.15). In conclusion, male circumcision could significantly protect males but not females from HIV acquisition at the population level. Male circumcision may serve as an additional approach toward HIV control, in conjunction with other strategies such as HIV counseling and testing, condom promotion, and so on.


Impact of Male Circumcision among heterosexual HIV cases: comparisons between three low HIV prevalence countries.

Chemtob D, Op de Coul E, van Sighem A et. al., Isr J Health Policy Res. 2015 Aug 4;4:36. doi: 10.1186/s13584-015-0033-8. eCollection 2015.

ABSTRACT:
BACKGROUND: Studies performed in high-HIV prevalence countries showed a strong epidemiological association between male circumcision (MC) and the prevention of HIV transmission. We estimated the potential impact of MC on the general heterosexual population in low-HIV prevalence countries. METHODS:
Cross-national comparisons, including data on newly diagnosed HIV cases among heterosexuals living in Israel (where almost all males undergo MC), to similar data from the Netherlands and France (where <10 % of males are circumcised) were performed. National data from HIV registers and Bureaus of Statistics for the period of 2004-2010, global rates, rates by sex, age, and year of HIV-diagnosis were compared. MC and potential biases were examined.
RESULTS: Annual rates of new HIV diagnoses per 100,000 were significantly lower in Israel compared to the Netherlands and France (for men: 0.26-0.70, 1.91-2.28, and 2.69-3.47, respectively; for women: 0.10-0.34, 1.10-2.10 and 2.41-3.08, respectively). Similarly, HIV-rates were much lower in Israel when comparing by age groups. Although Gross National Income per capita in 2010 was lower in Israel compared to the Netherlands and France, access to HIV testing and treatment were not different between countries. Also, the number of sexual-partners and condom-use in the general population showed a high similarity between the countries.
CONCLUSIONS: The lower rate of HIV among heterosexuals in Israel compared to the Netherlands and France might be explained by MC routinely practiced in Israel, since other parameters of influence on HIV transmission were rather similar between the countries. However, recommendation for systematic MC in low HIV prevalence countries requires further investigations.
For the full online article, see here.


Understanding the socio-economic and sexual behavioural correlates of male circumcision across eleven voluntary medical male circumcision priority countries in southeastern Africa.

Lau FK, Jayakumar S, Sgaier SK,BMC Public Health. 2015 Aug 22;15(1):813. doi: 10.1186/s12889-015-2135-1.

Abstract:
BACKGROUND: Male circumcision (MC) has been demonstrated to be effective and cost-effective for HIV/AIDS prevention. Global guidance to adopt this intervention was announced in 2007 for countries with high HIV/AIDS prevalence and low MC prevalence. However, scale up of voluntary medical male circumcision (VMMC) programs in MC priority countries have been slow. Many of these countries have particular cultural barriers that impede uptake of this effective intervention. This analysis explored correlates of MC status among men and their socio-economic, health and sexual behaviour factors using DHS data (2006-2011) from 11 MC priority countries.
METHODS: Our analysis included univariate unadjusted analyses for individual countries and the region (by combining all countries into one dataset) and a multiple logistic regression model.
RESULTS: Individual country results vary widely but alignment was mostly found between unadjusted analyses and multiple logistic regression model. The model found that men who are of the Muslim faith, reside in urban areas, have higher or secondary education attainment, hold professional occupations, and be in the richest wealth quintile are more likely to be circumcised. Circumcision is also positively correlated with lower reports of STIs, safe sexual behaviour, and HIV/AIDS prevention knowledge.
CONCLUSIONS: Since the data collected predate VMMC program launch in these countries, results can only indicate baseline associations. However, characteristics of these existing circumcision practices may be utilized for better population targeting and program management to achieve higher impact with this effective prevention strategy.
Online Abstrac


Lower HIV risk among circumcised men who have sex with men in China: Interaction with anal sex role in a cross-sectional study.

Qian HZ, Ruan Y, Liu Y, Milam DF et al.,J Acquir Immune Defic Syndr. 2015 Sep 21

Abstract: BACKGROUND: Voluntary medical male circumcision reduces the risk of HIV heterosexual transmission in men, but its effect on male-to-male sexual transmission is uncertain.
METHODS: Circumcision status of men who have sex with men (MSM) in China was evaluated by genital examination and self-report; anal sexual role was assessed by questionnaire interview. Serostatus for HIV and syphilis was confirmed.
RESULTS: Among1155 participants (242 known seropositives and 913 with unknown HIV status at enrollment), the circumcision rate by self-report (10.4%) was higher than confirmed by genital examination (8.2%). Male circumcision (by exam) was associated with 47% lower odds of being HIV seropositive (adjusted odds ratio [aOR], 0.53; 95% confidence interval [CI], 0.27-1.02) after adjusting for demographic covariates, number of lifetime male sexual partners, and anal sex role. Among MSM who predominantly practiced insertive anal sex, circumcised men had 62% lower odds of HIV infection than those who were uncircumcised (aOR, 0.38, 95%CI, 0.09-1.64). Among those whose anal sex position was predominantly receptive or versatile, circumcised men have 46% lower odds of HIV infection than did men who were not circumcised (aOR, 0.54, 95%CI, 0.25-1.14). Compared to uncircumcised men reporting versatile or predominantly receptive anal sex positioning, those who were circumcised and reported practicing insertive sex had an 85% lower risk (aOR, 0.15; 95%CI, 0.04-0.65). Circumcision was not associated clearly with lower syphilis risk (aOR, 0.91; 95%CI, 0.51-1.61).
CONCLUSIONS: Circumcised MSM were less likely to have acquired HIV, most pronounced among men predominantly practicing insertive anal intercourse. A clinical trial is needed.
Online Abstrac


In developed countries male circumcision prevalence is inversely related to HIV prevalence.

Morris BJ, Klausner JD,Isr J Health Policy Res. 2015 Aug 13;4:40. doi: 10.1186/s13584-015-0034-7.

ABSTRACT:
A study by Chemtob and co-workers found significantly lower prevalence of HIV amongst heterosexual men and women in Israel compared with the Netherlands and France. Risk factors for heterosexual HIV infection in these countries were similar, apart from one, namely, a strikingly higher prevalence of male circumcision (MC) in Israel compared with the Netherlands and France. It is now well established that MC protects heterosexual men against becoming infected with HIV during sexual intercourse with an infected woman. In epidemic settings, such as countries in sub-Saharan Africa, in which heterosexual contact is the primary driver for HIV infection, MC is being implemented to reduce HIV prevalence. The results of the new study by Chemtob and co-workers support the evidence and recent polices in the United States advocating MC to reduce the spread of HIV. While prevalence in developed countries is generally low, it is rising. In the long term, neonatal MC is the most desirable option, since not only is it simpler, safer, cheaper and more convenient than MC later, it provides immediate protection from infections, penile inflammation, genital cancers and physical problems. It is also cost-effective. European countries have not supported MC for its public health benefits. The new findings add to calls for European and other countries with low MC prevalence to consider developing evidence-based policies favoring MC in order to reduce HIV and other infections and diseases and at the same time reduce suffering, mortality and the cost of treating these.
Online Abstract


Voluntary medical male circumcision: A necessary surgical intervention in curbing HIV/AIDS.

Inon Schenker, Melvyn Westreich, Royal College of Surgeons Bulletin Volume: 97; Issue: 9, October 2015, pp. 378-381.

ABSTRACT:
Whether medical male circumcision (MMC) is an effective intervention for HIV prevention has been debated in the medical literature, but there are two epidemiological facts that are accepted by both proponents and opponents. First, despite all efforts to curtail the AIDS pandemic (eg anti-retroviral treatment expansion, distribution of free condoms, behavioural and educational interventions and HIV testing), more than 1.5 million new cases of heterosexually transmitted HIV (4,300 cases per day) were reported in Sub-Saharan Africa in 2012.1 Second, incidence and prevalence of HIV is consistently very low in populations that practise routine male circumcision (eg South Korea and The Philippines = 0.1%; Indonesia = 0.5%, Pakistan = 0.1%, Iran = 0.1%, Senegal = 0.5%, Israel = 0.2%).2 The hypothesis that mass adult male circumcision could be effective in changing the course of the AIDS epidemic3 was first discussed under WHO auspices on July 14 2000 in Durban, South Africa.4 This consultation instigated: three large randomised controlled trials (RCTs) in Africa, which proved that circumcision reduced the infection rate in sexually active men by more than 60%; a global effort to roll out voluntary medical male circumcision (VMMC) for HIV prevention, led by the WHO, UNAIDS, PEFPAR, the Bill and Melinda Gates Foundation and the World Bank; and increased research in to the role of VMMC in HIV prevention. Surgery has now come to the frontline in HIV prevention. Circumcision has proven to be a minor procedure that can be done safely under local anaesthesia. It has also been shown to be very effective in reaching two public health goals: HIV/AIDS prevention and strengthening health services in developing countries. If the goal of mass circumcision of 20 million African men is reached by the year 2025, there should be a 60% reduction in HIV infection. This translates to a reduction of 3.4 million new cases.5 This ambitious goal has aroused controversies concerning plans for adult and neonatal medical circumcision programmes. The objective of this paper is to dispel myths about VMMC, and bring evidence from peer-reviewed studies and our own experience participating in the global effort to prevent HIV/AIDS.
Online Abstract



Male circumcision to prevent syphilis in 1855 and HIV in 1986 is supported by the accumulated scientific evidence to 2015: Response to Darby.

Morris BJ, Wamai RG, Krieger JN et al., Glob Public Health. 2015 Nov 13:1-19

ABSTRACT:
An article by Darby disparaging male circumcision (MC) for syphilis prevention in Victorian times (1837-1901) and voluntary medical MC programs for HIV prevention in recent times ignores contemporary scientific evidence. It is one-sided and cites outlier studies as well as claims by MC opponents that support the author's thesis, but ignores high quality randomised controlled trials and meta-analyses. While we agree with Darby that risky behaviours contribute to syphilis and HIV epidemics, there is now compelling evidence that MC helps reduce both syphilis and HIV infections. Although some motivations for MC in Victorian times were misguided, others, such as protection against syphilis, penile cancer, phimosis, balanitis and poor hygiene have stood the test of time. In the absence of a cure or effective prophylactic vaccine for HIV, MC should help lower heterosexually acquired HIV, especially when coupled with other interventions such as condoms and behaviour. This should save lives, as well as reducing costs and suffering. In contrast to Darby, our evaluation of the evidence leads us to conclude that MC would likely have helped reduce syphilis in Victorian times and, in the current era, will help lower both syphilis and HIV, so improving global public health. Online Abstract


Study Says Circumcision Reduces AIDS Risk by 70%

By MARK SCHOOFS, SARAH LUECK and MICHAEL M. PHILLIPS Staff Reporters of THE WALL STREET JOURNAL July 5, 2005; Page A1


In a potentially major breakthrough in the campaign against AIDS, French and South African researchers have apparently found that male circumcision reduces by about 70% the risk that men will contract HIV through intercourse with infected women.

Other than abstinence and safer sex, almost nothing has been proved to reduce the sexual spread of HIV, the virus that causes AIDS. World-wide, the major route of HIV transmission for many years has been heterosexual sex.

Vaccine developers have said they would consider an AIDS vaccine with just 30% efficacy useful. But so far, no effective vaccine against the disease has been developed, leaving AIDS workers desperate for another tool to help them stem the tide of new infections, estimated at almost five million last year.

The circumcision findings were so dramatic that the data and safety monitoring board overseeing the research halted the study in February, about nine months before it would have been completed, on the grounds that it would be immoral to proceed without offering the uncircumcised control group the opportunity to undergo the procedure. While men were directly protected from infection by circumcision, women could benefit indirectly because circumcision would reduce the chances their partners would be HIV-positive.

Researchers in the field have been aware of the study's basic findings, but they haven't been published, so most experts haven't evaluated them. The British medical journal the Lancet decided against publishing the study, but for reasons unrelated to the data and scientific content, according to people familiar with the matter. Lancet officials, following standard policy at the journal, refused to comment on why the study was turned down.

The fact that an independent board ordered the study halted is considered a strong sign that the science is sound. Bertran Auvert, the French researcher who headed the trial, declined to discuss the findings but is expected to present them later this month at an International AIDS Society conference in Brazil.

Still, the fact that the research hasn't yet been published makes experts in the field wary about commenting. "Confirm, confirm, confirm," said Seth Berkley, a veteran HIV researcher and president of the International AIDS Vaccine Initiative. But if the study holds up, said Dr. Berkley, who wasn't involved with the research, it would be "quite important" because circumcision would be "an intervention that works over a person's lifetime and could reduce HIV in a community setting."

Assuming circumcision is as effective as the new study shows, it would still require careful implementation. In particular, health experts are concerned that men understand that circumcision can't fully protect them and that they maintain other preventive measures, such as safer sex.

"These preliminary results are quite interesting and we look forward to examining the data more closely, to looking at the technical aspects of the study and public-health implications if these results are confirmed by other trials," said Cate Hankins, chief scientific adviser to the United Nations AIDS agency, UNAIDS.

More than 30 previous studies have suggested a relationship between circumcision and lower rates of HIV infection. In Kenya, for example, HIV prevalence is much higher among the Luo people, who don't practice circumcision, than among the Kikuyu, who do.

And there are strong biological theories as to why. For example, a type of cell that HIV targets, called the Langerhans cell, lies close to the delicate underside of the foreskin, whereas the head of a circumcised penis tends to develop a thick layer of outer skin that may armor it against HIV. Another theory: Rather than acting against HIV itself, circumcision may help prevent other sexually transmitted diseases that are known to facilitate the acquisition of HIV.

Despite these theories, no study until now has been able to prove that circumcision reduces the chances of contracting HIV. Longtime advocates of the benefits of circumcision note that performing such a study has always faced resistance because of the sensitive cultural issues involved as well as the challenge of persuading a significant number of men to undergo the procedure.

The new research was designed to test the hypothesis by the most rigorous possible method: a randomized, controlled clinical trial.

It was conducted with more than 3,000 HIV-negative men ages 18 to 24 in a South African township called Orange Farm. Half of the men were randomly assigned to be circumcised and the other half to remain uncircumcised as controls. The study, headed by Dr. Auvert, a researcher at the French National Institute of Health and Medical Research and at the University of Versailles Saint-Quentin, originally planned to follow the men for 21 months. But after all the men had been followed for a year -- and about half of them for the full 21 months -- the data showed the circumcised group fared far better. For every 10 uncircumcised men in the study who contracted HIV, only about three circumcised men did so, according to two people familiar with the research and a draft of the study reviewed by The Wall Street Journal.

Stopping trials is common when an intervention is clearly shown to be effective. Indeed, the result of the South African trial is likely to spark discussion of whether to halt or modify two other major studies of circumcision and HIV under way in Kenya and Uganda, funded by the National Institutes of Health.

Ronald Gray, lead researcher on the Uganda trial, said, "It would be extremely unwise" to stop the Kenya and Uganda trials at this stage because "medicine has been burned in the past when policy is based on a single trial."

It isn't clear how the new study, if confirmed, would influence U.S. policy. Circumcision wouldn't affect IV drug users who get infected by sharing syringes, a group that accounts for a large proportion of American HIV cases. Also, the South Africa study didn't evaluate whether circumcision would offer any protection to gay men, who make up another large proportion of American cases. Any direct benefit to gay men would almost certainly be restricted to the insertive partner in anal intercourse, not the receptive partner.

In countries where male circumcision is uncommon and heterosexual HIV rates are high or rising rapidly, the procedure could be a powerful way of reducing the spread of the disease, the new study shows.

Even so, researchers warn of potential pitfalls in trying to put the findings into practice. First, circumcision doesn't make a person immune to infection. Indeed, if men abandon safer sex practices because they think the surgery completely protects them, then HIV transmission could rise.

"It will not take very much of an increase in risk behavior to overcome the benefit from circumcision," said Carolyn Williams, an American researcher involved in the Kenya circumcision study. AIDS experts insist that circumcision will have to be accompanied by intensive counseling.

Secondly, AIDS researchers worry that circumcisions performed in unsanitary conditions could lead to dangerous complications.

And while many Africans come from cultures that practice circumcision, many others don't. Would large numbers of men in noncircumcising cultures consent to go under the knife simply to reduce their risk of acquiring HIV?

"It's a surgical procedure on an organ that, you know, conjures up a lot of feelings in people," said Robert Bailey, the principal investigator in the Kenya study. "It's not just a shot in the arm."

Write to Mark Schoofs at mark.schoofs@wsj.com1, Sarah Lueck at sarah.lueck@wsj.com2 and Michael M. Phillips at michael.phillips@wsj.com3

Online Article


Other Articles of interest

Uncircumcised Men Have More HIV
Interview with Alan Landay, PhD, immunologist, 2002

Male Circumcision: Cutting the Risk?
Bob Huff, American Foundation for AIDS Research, August 2000



Online Medical Articles and Abstracts

  1. Toward a Systematic Approach to Generating Demand for Voluntary Medical Male Circumcision: Insights and Results From Field Studies.
    Sgaier SK, Baer J et al , Glob Health Sci Pract. 2015 Jun 17;3(2):209-29. doi: 10.9745/GHSP-D-15-00020
  2. Estimating the impact of the US President's Emergency Plan for AIDS Relief on HIV treatment and prevention programmes in Africa.
    Heaton LM, Bouey PD et al , Sex Transm Infect. 2015 Jun 8. pii: sextrans-2014-051991
  3. Male Circumcision Shown to Prevent HPV Infections in Female Partners.
    Johns Hopkins School of Medicine, June 15, 2015
  4. Male circumcision for HIV prevention in India: emerging viewpoints and practices of health care providers.
    Sinha A, Chandhiok N et al, AIDS Care. 2015 May 22:1-3.
  5. Circumcision Status and Risk of HIV Acquisition during Heterosexual Intercourse for Both Males and Females: A Meta-Analysis.
    Lei JH, Liu LR et al , PLoS One. 2015 May 5;10(5):e0125436.
  6. Wimbo: implications for risk of HIV infection among circumcised fishermen in Western Kenya.
    Ombere SO, Nyambedha EO et al , Cult Health Sex. 2015 Mar 16:1-8.
  7. Voluntary medical male circumcision for HIV prevention and early resumption of sexual activity: a literature review.
    Kamath V, Limaye RJ, CAIDS Care. 2015 Mar 4:1-4.
  8. K Smit , Brinkman K et. al. Future challenges for clinical care of an ageing population infected with HIV: a modelling study. Lancet Infect Dis. 2015 Jun 9. pii: S1473-3099(15)00056-0
  9. Weiss SM, Zulu R et al. A cluster randomized controlled trial to increase the availability and acceptability of voluntary medical male circumcision in Zambia: The Spear and Shield Project. Lancet HIV. 2015 May 1;2(5):e181-e189.
  10. Acceptability of male circumcision as a tool for preventing HIV infection in a highly infected community in South Africa.
    Lagarde E, Dirk T, Puren A, Reathe RT, Bertran A, AIDS 2003 Jan 3;17(1):89-95
  11. Circumcision and STD in the United States: cross sectional and cohort analyses
    Diseker RA, Peterman TA, Kamb ML, Kent C, Zenilman JM, Douglas JM, Rhodes F, Iatesta M, Sex Transm Infect 2000 Dec;76(6):474-9
  12. Male Circumcision and Risk of HIV Infection in Sub-Saharan Africa: a Systematic Review and Meta-Analysis"
    H.A. Weiss, M.A. Quigley and R.J. Hayes

  13. Dynamics of Male Circumcision Practices in Northwest Tanzania
    Soori Nnko, Robert Wahsija, Mark Urassa, J.Ties Boerma, Sex. Trans. Dis. 2001;28:214-218.

  14. Vitamin A and risk of HIV-1 seroconversion among Kenyan men with genital ulcers
    MacDonald KS, Malonza I, Chen DK, Nagelkerke NJ, Nasio JM, Ndinya- Achola J, Bwayo JJ, Sitar DS, Aoki FY, Plummer FA, AIDS 2001 Mar 30;15(5):635-63.

  15. How does male circumcision protect against HIV infection?
    R. Szabo and R.V. Short, BMJ 2000; 320:1592-4.

  16. Male circumcision and HIV infection: 10 years and counting,
    D.T. Halperin and R.C. Bailey, Lancet 1999; 354:1813-5.

  17. Controversy Over Male Circumcision and HIV Transmission in Developing World
    Ronald Baker, PhD


Other Excerpts

Sexual Transmission Of HIV
Royce FA, Sena A, Cates W Jr., Cohen MS New England Journal Of Medicine 1997: 336(15); 1072-1078

"Male circumcision consistently shows a protective effect against HIV infection. This may be due to the abundance of Langerhans' cells in the foreskin or to a receptive environment for HIV in the sulcus between the foreskin and the glans. The prevalence of HIV infection is 1.7 to 8.2 times as high in men with foreskins as in circumcised men, and the incidence of infection is 8 times as high. A greater proportion of sex partners of uncircumcised men than of circumcised men are infected with HIV, which suggests that the presence of the foreskin may also increase infectiousness."


Circumcision Protects Against HIV Infection Westport, Jan 28, 1997 (Reuters): AIDS 1997: 11; 73-80

Male circumcision appears to have protective effect against HIV infection, according to the Tanzania-Netherlands Project to Support AIDS Control in Mwanza region (TANESA).
After controlling for confounding variables," Dr. Marc Urassa found a "...modest but significant reduction of the HIV prevalence among circumcised men."


Evidence That Circumcision Reduces Susceptibility To HIV Infection Called Substantial Westport, Jul 11, 1996 (Reuters)

There is now a "...substantial body of evidence..."that male circumcision lowers susceptibility to HIV infection, Dr.Stephen Moses told conference participants at the XI International Conference on AIDS Wednesday.
Dr.Moses concluded that the fact that male circumcision reduces susceptibility to HIV infection "...may explain part of the wide geographic and population-level variability in observed HIV transmission."


The African AIDS Epidemic

John C. Caldwell and Pat Caldwell
Scientific American 1996: 273(3); 62-68

Health Transition Center of the National Center for Epidemiology and Population Health at the Australian National University in Canberra.
"Over the past three years, however, we have examined the methodology of the papers as well as the anthropology sources and determined that the findings are sound. Also, in continuing investigation we have found very little support for the charge that circumcision data are no longer relevant. The link between the lack of circumcision and elevated levels of HIV infection appears robust.
In some parts of the AIDS belt, nearly all men are uncircumcised - a situation unlike almost anywhere else in Africa. Thus we conclude that in the AIDS belt, lack of male circumcision in combination with risky sexual behavior, such as having multiple sex partners, engaging in sex with prostitutes and leaving chancroid untreated, has led to rampant HIV transmission".


Circumcision and sexually transmitted diseases

L.S. Cook, L.A. Koutsky, K.K. Holmes
Am J Public Health 1994: 8(2); 197-201

OBJECTIVES. New evidence linking lack of circumcision with sexually transmitted human immunodeficiency virus revives concerns about circumcision and other sexually transmitted diseases. This study was undertaken to assess the relationship between circumcision and syphilis, gonorrhea, chlamydial infection, genital herpes, nongonococcal urethritis, and exophytic genital warts. METHODS. A cross-sectional study of 2776 heterosexual men attending a sexually transmitted disease clinic in 1988 was used to investigate the relationship between circumcision and sexually transmitted diseases. Subjects with specific sexually transmitted diseases and those without such diseases were compared after adjustment for age, race, zip code of residence, other sexually transmitted diseases, and number of sexual partners. RESULTS. A positive relationship was observed between uncircumcised status and both syphilis and gonorrhea. A negative relationship was found between warts and lack of circumcision. No apparent relationship was noted between uncircumcised status and genital herpes, chlamydial infection, or nongonococcal urethritis. CONCLUSIONS. Uncircumcised men were more likely than circumcised men to have syphilis and gonorrhea and were less likely to have visible warts.


Genitourinary Manifestation of AIDS

Staiman VR, Delbert JK, Lowe FC Infections Urology 1996: 9(3); 73-78,92

"An uncircumcised male has twice the risk of being infected that a circumcised male has. Because the foreskin is associated with high concentrations of macrophages and lymphocytes, these cells are targets for HIV virus. The foreskin also provides a protected environment and a larger surface area for prolonged exposure between the genital epithelium and infected genital secretions. Also, the uncircumcised penis does not have a thick stratum corneum layer of the glans, which develops after circumcision, this layer protects against abrasions. Finally, the uncircumcised male has an increased risk of acquiring other sexually transmitted diseases that can increase the likelihood for HIV transmission."


Male Circumcision And Susceptibility To HIV infection Among Men In Tanzania

Urassa M, Todd J, Boerma JT, Hayes R, Isingo R   AIDS 1997: 11(3); 73-80

"Male circumcision has a protective effect against HIV infection in this population, which may be stronger in urban areas and roadside settlements than in rural areas. Ethnic group and religious denomination are no longer the sole determinants of male circumcision."