Male circumcision: new data supporting protective mechanism

4 February 2010. Related: HIV prevention and transmission.

Simon Collins, HIV i-Base

The protective mechanism for reducing heterosexual HIV transmission to circumcised men has been attributed to two factors relating to the properties of the inner foreskin:  a thinner keratin layer reducing the physical barrier and a higher concentration of CD4 and Langerhans cells that are primary targets for infection.

A third factor may be that the foreskin prolongs the time that fluid that contains HIV remains in contact with genital tissue. In theory, the size of the foreskin should also positively correlate to the risk from these mechanisms, and this is supported by results from a study published in the 23 October edition of the journal AIDS. [1]

HIV infection rates were collected from 965 men in Rakai, Uganda, who were recruited for two randomised circumcision studies. These men were initially HIV negative and followed for a total of 3920 person years, prior to circumcision as part of the trial protocol. The results from these trials have already been reported. [2, 3]

After circumcision, the foreskin surface area was calculated (length x width; cm²) and infection rates prior to circumcision were calculated by quartile. Men who became infected compared to those who remained HIV negative were found to have a significantly greater foreskin surface area (mean 43.3 (+2.1) vs 36.8 (+0.5) cm² (p=0.01).

HIV incidence/100 person years (PY) was 0.80, 0.92, 0.90 and 2.48 for men with foreskin surface areas in the lower (7.0-26.3 cm²), second (26.4-35.0 cm²), third (35.2-45.5 cm²) and upper quartiles (45.6-99.8 cm²) respectively.

The incidence rate ratio (IRR) of HIV acquisition, after adjusting for age, education, religion, number of sex partners and condom use, was significantly higher for men in the highest compared to the lowest quartiles of foreskin surface area (IRR 2.37; 95%CI 1.05-5.31). There was, however, no significant difference in HIV incidence between the lower three quartiles. In the adjusted analysis, older age (IRR 4.16; 95%CI 1.55, 11.19, and IRR 4.00; 95%CI 1.46, 10.74; for ages 25-30 and >30 respectively, each compared to 15-24 years), lower education level (0.40; 0.18, 0.91; secondary/tertiary vs primary/none) and catholic religion (IRR 0.37; 0.16, 0.82; Catholic vs non-Catholic) were also significantly associated with risk of HIV acquisition.

The authors concluded that their findings, in addition to the observational studies and randomised trials, add plausibility to the hypothesis that the foreskin is a tissue vulnerable to HIV acquisition.

They suggested that minimising retention of residual foreskin tissue after male circumcision using dorsal slit and sleeve procedures rather than the forceps-guided procedure (which leaves 0.5-1.0 cm of mucosal skin proximal to the corona) is a theoretical concern. However, they also reported that they did not observe any increased risk of HIV acquisition among men with smaller foreskin surface areas that were substantially larger than residual tissue retained after circumcision surgery.

COMMENT

While the study states that these findings need to be replicated in other studies, it is difficult to see how this could occur.

Firstly, although circumcision studies have shown protection against HPV, HSV and syphilis, men primarily want to be circumcised in order to reduce their risk of HIV infection, and should be told if they are HIV positive at the time of surgery.

It is unclear whether the men in this study would have undertaken circumcision, had they been made aware that they had already caught HIV prior to the intervention.

Secondly, now that circumcision had been proven to reduce heterosexual transmission in high prevalence settings, it is difficult to see why
participants would be followed for any significant period prior to surgery.

References

1. Kigozi G et al. Foreskin surface area and HIV acquisition in Rakai, Uganda (size matters). AIDS. 23(16):2209-2213, October 23, 2009. doi: 10.1097/QAD.0b013e328330eda8.
2. Gray RH et al. Male circumcision for HIV prevention in men in Rakai, Uganda: a randomised trial. Lancet 2007; 369:657-666.
3. Wawer MJ et al. Circumcision in HIV-infected men and its effect on HIV transmission to female partners in Rakai Uganda: a randomised controlled trial. Lancet 2009; 374:229-237.