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How can Circumcision Prevent HIV?

Medical Male Circumcision (MMC) is currently recommended for men living in areas where HIV rates are high and prevention tools are scarce. Some men, understandably, are unwilling to undergo MMC. Nyaradzo Chigorimbo-Tsikiwa, with the Desmond Tutu HIV Centre and the Division of Immunology, is researching the cellular and molecular composition of the foreskin. The goal is to identify how HIV penetrates the foreskin tissue and maybe find a solution for these men who would prefer to remain uncircumcised.

Nyaradzo Chigorimbo-Tsikiwa for DTHF research meeting May 2017 | Caroline Reid

It has been shown that after a medical male circumcision (MMC), randomised clinical studies report a 60% risk reduction in HIV acquisition. Researchers are not certain why the removal of the foreskin leads to lower incidences of HIV but there are some theories. One suggests that it reduces the number of  HIV target cells (including Langerhans’ cells)  by removing the foreskin during MMC. Secondly,  HIV can’t penetrate normal healthy skin but if there are abrasions then they could provide a point of entry in uncircumcised men. In addition, the inner foreskin removed during MMC has been found by researchers to be susceptible to infection by the virus due to its physiology.

a) Flaccid penis and b) erect penis and locations where HIV can enter the body | C Dezutter-Dambuyant/SG McCoombe & RV Short, AIDS

Chigorimbo-Tsikiwa takes foreskin samples from circumcised men with and without asymptomatic STIs. Studying these tissues provided insight on how HIV can infect a man through his foreskin.

The foreskin has an inner part which is in direct contact with the penis before circumcision and the outer part which covers the head of the penis. Chigorimbo-Tsikiwa together with Professor Clive Gray and others have found some important differences between the inner and outer foreskin using proteomics (the study of proteins) and on a cellular level. The first difference was in the proteins that function as barriers. The second difference was that the outer layer of the foreskin has a thicker layer of keratin than the inner foreskin. Keratin is a protective protein found in skin that makes it impenetrable. An important difference they found was also in increased numbers of HIV target cells in men with asymptomatic STIs. These few extra cells could make all the difference to infection susceptibility.

Distribution of Immune Cells (Langerhans’ cells, green) in the Outer Foreskin under a protective layer of keratin (dark blue) | C Dezutter-Dambuyant/SG McCoombe & RV Short, AIDS

It is possible that MMC can prevent HIV because it removes inner foreskin tissue that is susceptible to the virus. This would explain why men who undergo MMC have lower rates of HIV.

The next step is to figure out which genes are involved in prevention. The final goal is to figure out which compounds will prevent HIV from interacting with these immune cells. Eventually, this could be incorporated into a product e.g. a microbicide gel that the man could apply to the penis for protection during intercourse.

We wish Chigorimbo-Tsikiwa the best of luck with the next stages of her research.

 

Written by Caroline Reid