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.

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

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1. 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
2. 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
3. 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

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

5. 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.

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

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

8. 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".