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Biology not behaviour could explain reduced risk of HIV infection for circumcised men (p 1039)

March 24, 2004

Research from India published in this week's issue of THE LANCET suggests that circumcised men could be over six times less likely than uncircumcised men to acquire HIV infection. The study also shows how the explanation for this decreased risk in circumcised men is likely to be biological rather than behavioural, with thin tissue in the foreskin being the likely target for viral activity.

Previous research has shown that circumcised men have a lower risk of HIV-1 infection than uncircumcised men. Laboratory findings have suggested that the foreskin is enriched with HIV-1 target cells. However, other research has suggested that circumcision could be an indicator for low-risk sexual behaviour.

Robert C Bollinger and colleagues from Johns Hopkins University Medical School, USA, and the National Aids Research Institute, Pune, India, observed how uncircumcised men attending sexually transmitted infection clinics in India were over six times more likely to acquire HIV infection than men who had been circumcised. All men were HIV-negative when first assessed; most men were assessed three times after initial assessment for around a year. No protective effect of circumcision against herpes simplex virus type 2, syphilis, or gonorrhoea was found.

Dr Bollinger comments: "These data confirm previous findings that male circumcision reduces the risk of HIV-1 acquisition. This analysis expands on earlier studies by including laboratory-defined incident STIs as outcomes in the analysis, as well as by including risk behaviour to control for other potential differences between circumcised and uncircumcised men. A unique and important finding from this study was a highly significant and specific protective effect of male circumcision on the risk of HIV-1 acquisition. Our data failed to show a significant protective effect of circumcision on the risk of the other STIs. These epidemiological data lend support to the hypothesis that male circumcision protects against HIV-1 infection primarily due to removal of the foreskin, which contains a high density of HIV-1-specific cellular targets, including CD4+ T-lymphocytes and Langerhans' cells, which are easily accessible to the virus through the thin layer of keratin overlying the inner mucosa".

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