Protective effect of circumcision is sustained for at least 3.5 years; also works against HPV

The protective effect of circumcision against HIV infection remains unchanged for at least 42 months after the operation, the lead investigator from the randomised controlled trial (RCT) in Kisumu, Kenya, told the XVII International AIDS Conference on Thursday in Mexico City.

And in an accompanying presentation, one of the researchers from another of the RCTs, the first one to report from Orange Farm, South Africa, told the conference that circumcision also offered a significant degree of protection against the genital wart virus HPV, some forms of which can cause anal and cervical cancer.

There is no reason to think that the protective effect of circumcision against HIV should be anything other than life-long. However, noted the Kisumu trial’s principal investigator Robert C Bailey, there had been concerns that all three RCTs of circumcision had been stopped before they reached full-term, and sceptics questioned whether there was any evidence that the effect persisted beyond the two-year span of the trials.

Bailey reported that the result of a 42-month follow-up from the study showed that the protective effect was maintained. Indeed he had revised his estimate of its effect upwards from 53-59% to 65-70%, partly because a couple of apparent seroconversions in circumcised men had turned out to be false-positives.

Twenty-four month results from the Kisumu trial, in which 2784 young men were randomised either to immediate circumcision or to the offer of circumcision after the study ended, showed a 53% protective effect of male circumcision on an intent-to-treat analysis (i.e. treating all participants who were to be circumcised as if they actually had been), and 59% on an as-treated analysis (only including men who actually were circumcised).

At this point 22 men who were circumcised had caught HIV and 47 men who remained uncircumcised had been infected. See this report for more on the Kisumu study.

In fact the true figures were that 18 circumcised and 45 uncircumcised men were infected, due partly to a couple of circumcised men not actually having the operation, and partly due to several false-positive results. This increased the protective effect to 60%.

After the end of the RCT, men in the control group could be circumcised, and 42% of them chose to do so. When asked why more did not choose circumcision knowing the result, Bailey commented that it was partly because this was a highly mobile population of young men and that many had moved away to Nairobi and Mombasa.

By month 42, 1545 (55%) of the original trial group was still available for follow-up, evenly split between those who had originally been in the circumcision arm and those who had been controls.

During the next 18 months there were five more infections in the circumcised men and 17 more in men who remained uncircumcised. This gave an infection rate of 2.6% in circumcised men and 7.4% in uncircumcised men, pushing the protective effect up further to 70%.

When only men who had originally been randomised to circumcision were counted, this fell slightly. At present the annual incidence rate among circumcised men has been calculated as 0.77% a year, and among uncircumcised men 2.37% a year, giving a protective effect of 65%.

Bailey said the trial participants would be followed up until September 2009, providing five years of data.

“These results strengthen the backing to provide safe, free circumcision in a variety of settings to men in generalised epidemics as soon as possible,” commented Bailey.

In the following presentation Dirk Taljaard, an investigator on the South African RCT in Orange Farm presented a substudy of the effect of circumcision on three sexually transmitted infections (STIs) – gonorrhoea, trichomoniasis and human papilloma virus (HPV). See this report for details of the original study.

Men (were tested at the 21 months’ follow-up visit when the study was ended. Men had urethral swabs and urine samples taken at their last follow-up visit, and samples were tested using PCR.

Circumcision offered no protection against gonorrhoea: infection rates in uncircumcised and circumcised men were 10.3% and 10.4% respectively.

It appeared to offer a degree of protection against trichonomiasis: 3.1% of uncircumcised men versus 1.7% of circumcised men were infected at follow-up, offering a protective effect of 46%, which was of borderline statistical significance.

However it did offer a significant degree of protection against infection by 13 types of high-risk HPV: high-risk meaning associated with cervical, anal and penile cancer.

At follow-up, 24.8% of uncircumcised and 15.8% of circumcised men had become infected with new types of HPV, and this 47% protective effect was statistically significant (p = 0.0012). After adjusting for confounders the protective effect became smaller (36%) but was still statistically significant.

This study is the first to show such a protective effect of male circumcision and explains why women with circumcised partners are at less risk of high-risk wart virus and trichomoniasis infections. The French and South African authors suggest these findings reinforce the need to implement male circumcision in Africa.

References

Bailey RC et al. The protective effect of male circumcision is sustained for at least 42 months: results from the Kisumu, Kenya trial. XVII International AIDS Conference, Mexico City, abstract THAC0501, 2008.

Auvert B et al. Effect of male circumcision on human papilloma virus, neisseria gonorrhoeae and trichomonas vaginalis infections in men: results from a randomized controlled trial. XVII International AIDS Conference, Mexico City, abstract THAC0502, 2008.