AIDSWEEKLY Plus; September 30, 2002
Staff Medical Writers

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 with circumcised men. However, why circumcision plays a protective role against acquisition of HIV has been unknown.

A study published in the September 2002 issue of the American Journal of Pathology¹ 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 contain high concentrations of the cells targeted by HIV. The foreskin tissue contained higher densities of CD4+ T cells, macrophages 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, MD, viral pathologist in the division of infectious diseases at Children's Memorial Hospital, there are logical, but as yet unproved 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 with the outer mucosal surface predisposed the foreskin to infection.

The authors mentioned 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 1400 African males age 18-24 who will be circumcised with 1400 in the same city who are not circumcised.

Bailey's team will take 2 years to recruit all the young men and will follow each group for 2 years, providing them with HIV prevention counseling and free medical treatment. After 4 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 uncircumcised individuals and HIV acquisition indicate that strong consideration should be given to integrating male circumcision information and services with other HIV preventive methods.

This article was prepared by AIDS Weekly editors from staff and other reports.

Reference

1. Patterson BK, Landay A, Siegel JN, et al., "Susceptibility to human immunodeficiency virus-1 infection of human foreskin and cervical tissue grown in explant culture", Am J Pathol 2002 Sep;161(3):867-73

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