The reduction in HIV infection risk after circumcision may be the result of a decline in bacteria on the surface of the penis that assist the process of infection, according to findings from the research team that helped establish the evidence base for using male circumcision as an HIV prevention strategy.
If this is the case, and if the bacteria can be eliminated without removing the foreskin, such a procedure might provide an important non-surgical alternative to circumcision in settings where the procedure is culturally unacceptable or difficult to implement.
The recent study, which appears in the January 2010 edition of PLoS ONE, analysed penile swabs taken from twelve participants in the Rakai, Uganda circumcision study, which enrolled almost 5,000 uncircumcised HIV-negative men and randomised half of them to be circumcised.
The twelve members of the follow-up study cohort were randomly chosen from the subset of men who had undergone circumcision and were still HIV-negative one year after the procedure.
Many different types of bacteria live on and in the human body, and changes in levels of these bacteria may affect health through complex pathways that are not well understood.
The Rakai study team used penile swabs taken before circumcision and one year after circumcision to examine how the twelve men’s bacterial make-up had changed. They found that the samples contained more than 40 distinct bacterial families, including both aerobic (oxygen-requiring) and anaerobic (non-oxygen-requiring) bacteria.
The most notable difference between the pre-circumcision and post-circumcision samples was a major reduction in anaerobic bacteria. The researchers proposed that the removal of the foreskin may have eliminated a micro-environment that fosters the growth of anaerobic bacteria.
Their hypothesis is bolstered by the observation that the female partners of circumcised men are less likely to develop bacterial vaginosis, a vaginal infection associated with the presence of a higher-than-normal level of anaerobic bacteria.
The specific way in which anaerobic bacteria may facilitate HIV transmission is hypothesised to involve Langerhans’ cells, a component of the immune system that functions in two different ways in relation to HIV. When inactivated Langerhans’ cells encounter particles of HIV, they work against HIV. However, Langerhans’ cells that have become activated play a role in helping the virus infect the body.
Anaerobic bacteria may activate Langerhans’ cells in the genital area, which would help explain why circumcision bestows partial protection against HIV. Removal of anaerobic bacteria via circumcision may result in less Langerhans’ activation, leaving the virus with a smaller gateway to infection.
The researchers believe that their discovery may have significant public health implications, in part because of the limited demand for male circumcision, which is thought to reduce a man’s risk of acquiring HIV through heterosexual sex by about 60%.
“Large-scale population-based male circumcision programs may not always be feasible due to cultural, logistical, and financial barriers,” they write. “Thus, it is important to better understand the biological mechanisms by which male circumcision reduces the risk of HIV infection as this may lead to the development of novel, non-surgical prevention strategies.”
According to a press release announcing the article’s publication, 70% of men worldwide are estimated to be unlikely to undergo circumcision.
The press release noted that the reduction in anaerobic bacteria is only one of multiple proposed explanations for why circumcision makes it harder for HIV infection to occur. Following circumcision, the top layer of the inner foreskin becomes thicker, perhaps providing a more effective barrier against HIV.
Also, reducing the amount of mucosal tissue exposed to vaginal secretions could result in fewer opportunities for HIV to interact with the immune cells that it targets.
“These potential explanations are not mutually exclusive and may work in concert to reduce HIV risk,” said Dr. Lance Price, one of the article’s authors.
The research team plans to look for specific bacteria associated with greater HIV risk, and to explore how such bacteria might be eliminated.
Price LB et al. The effects of circumcision on the penis microbiome. PLoS ONE 5: e8422, 2010.