Jury still out on whether circumcision protects gay men against HIV

A meta-analysis of studies of circumcision in gay men and men who have sex with men (MSM) has not found sufficient evidence to show that being circumcised reduced their risk of acquiring HIV. Although it finds a small reduction in the risk of HIV infection in circumcised men, this is not statistically significant - in other words it could just be a chance finding. Furthermore, the study, published in the Journal of the American Medical Association, found that although circumcised men who were exclusively insertive for anal sex had a lower risk of infection with HIV, the difference with uncircumcised men was still not statistically significant and could have been chance.

But the researchers did find that studies conducted before the introduction of effective HIV therapy showed a statistically significant association between circumcision and lower HIV risk. They also found that studies that were conducted more rigorously were more likely to find that circumcision had a protective effect.

The meta-analysis, by Gregorio Millett and colleagues from the US Centers for Disease Control, covered 17 studies conducted between 1989 and 2007. The analysis also included some unpublished results. The studies included 27,816 circumcised and 25,751 uncircumcised men (52% circumcised). Nine were conducted in North America while four out of the other eight were conducted in developing countries in Asia and South America. Circumcision prevalence in individual studies varied from 4% to 88% but the proportion of men circumcised did not appear to affect results.

Six studies also looked at the relationship between circumcision and other sexually transmitted infections (STIs) and one looked only at other STIs and not HIV.

HIV prevalence in individual studies ranged from 5% to 72% and in the three studies that were able to report HIV incidence – the rate of new infections - it ranged from 0.8% to 2.8% a year.

Overall the studies produced a non-statistically-significant reduction of 14% in HIV infection. A subset of studies that looked at results in 2238 men who only had insertive sex found a 29% reduction in HIV infection among circumcised men, but this difference was also not statistically significant.

However, in studies conducted prior to the introduction of effective HIV treatment, the authors found a 53% reduction in HIV infection in circumcised men. The authors point out that this reduction is “comparable” to that seen in the randomised controlled trials of circumcision in heterosexual men. In contrast there is no association whatsoever between circumcision and HIV in more-recent studies. The authors also found a non-statistically-significant reduction of 51% in HIV infections in circumcised men in studies conducted in developing countries, where antiretroviral therapy is less available.

The authors suggest that higher rates of unsafe sex and resultant HIV and STI infection in gay men since HIV treatment became available may have obscured the relatively small benefit of circumcision.

They also found a trend to more statistically significant results as study quality increases, with a non-significant 32% reduction in HIV infection in circumcised men seen in studies where circumcision and HIV infection were confirmed by genital examination and testing.

Finally, the authors found no association between circumcision and reductions in any other STI. Indeed in post-1996 studies and in higher-quality studies, there was a nearly significant increase in STIs in circumcised men.

The investigators suggest that studies could be conducted in men who primarily have insertive sex or in resource-poor settings, though there would be considerable ethical issues in the latter case.

In a separate editorial, Sten Vermund and Han-Zhu Qian of the Institute of Global Health urge further trials to settle the question of whether circumcision offers any protection against HIV to gay men once and for all. They comment that “only further research can answer…the question as to whether MSM should be circumcised to reduce their HIV risk.”

However they also express concerns that such research might face opposition.

“The meta-analysis”, they say, “is likely to be used by both advocates and detractors of clinical trial investment; some will argue that the likely benefit is too modest to justify a multimillion dollar trial while others will argue that only a clinical trial will answer this important HIV prevention question.”