Systematic analysis suggests that circumcision helps protect MSM from infection with HIV

Circumcision protects men who have sex with men (MSM) from infection with HIV, according to a systematic review and meta-analysis of studies published in The Lancet Global Health. Overall, circumcision was associated with a 23% reduction in the odds of infection with HIV.

The protective effect of circumcision was primarily seen in studies conducted in low- and middle-income settings, regions where sex between men is often highly stigmatised and where few HIV prevention resources are targeted at MSM. The authors therefore suggest that MSM could – without risk of stigma – be enrolled in existing voluntary male circumcision programmes targeted at the general population.

“MSM in countries of low and middle income could benefit from advances in cheap, safe, and convenient circumcision techniques,” comment the authors. “Because circumcision as an HIV prevention measure targets all men regardless of sexual orientation, MSM in countries of low and middle income seeking circumcision would most likely experience less stigma when accessing this service.”

There was also evidence that circumcision provided MSM with protection against herpes simplex virus (HSV), and HIV-positive men had a reduced risk of penile human papillomavirus (HPV).

Well-designed randomised control trials conducted in Africa showed that male circumcision reduces the risk of female-to-male HIV transmission. The underlying biological reason is likely to be the high density of cells targeted by HIV in the inner mucosa of the foreskin.

However, it is unclear if circumcision also protects MSM from infection with HIV. The results of individual studies are conflicting, and meta-analyses of the data have provided inconclusive answers.

The last such analysis was conducted as recently as 2018. This showed that circumcised MSM had a 20% reduction in the odds of infection with HIV. A team of investigators led by Dr Tanwei Yuan of Sun Yat-sen University, China, updated this analysis, taking into account numerous studies neglected in the 2018 meta-analysis.

They identified a total of 62 observational studies involving MSM that examined HIV and/or STI incidence and/or prevalence in MSM according to circumcision status. The studies were conducted between 1989 and 2016.

The number of MSM enrolled in each study ranged from 40 to over 25,000. Average age ranged from 18 to 46 years. Circumcision prevalence varied from 4 to 96%. Consistent condom use was between 12 and 83%.

A total of 45 studies examined the association between circumcision and HIV status in MSM. Most of the studies – 29 – did not find statistically significant associations. Two studies found that circumcision protected men who were exclusively insertive for anal sex. Two studies found a protective effect of circumcision, but only for bisexual men. In contrast, one study found that circumcised MSM had an increased risk of being HIV positive.

A total of 105,009 MSM were included in the meta-analysis. This showed that, overall, circumcision reduced the odds of HIV infection by a significant 23% (OR = 0.77; 95% CI, 0.67-0.89). This protective effect became apparent after 2011. Interestingly, the association between circumcision and lower HIV was only seen in low- and middle-income countries (OR= 0.58; 95% CI, 0.41-0.83). No significant protective effect was seen in high income countries (OR = 0.99; 95% CI, 0.90-1.09).

The investigators suggest several reasons why the protective effect of circumcision was only seen in low- and middle-income countries:

• Stability and segregation in anal sex role, i.e. men more likely to be exclusively “top” in these settings than in higher income countries.
• High proportion of bisexual men. Other research has found that between 40 and 70% of MSM in low- and middle-income countries also have sex with women.
• High HIV prevalence.
• Lack of HIV prevention resources for MSM in low- and middle-income countries.

The overall protective effect of circumcision against HIV infection was slightly increased when the investigators restricted their analysis to the 14 studies that adjusted for potential confounders (OR = 0.64; 95% CI, 0.45-0.93).

There were 29 studies examining the association between circumcision and other STIs. Once again, the majority found no association. However, several studies showed a reduced risk of HSV or penile HPV.

The 27 studies (61,411 MSM) included in the STI meta-analysis showed that there was marginal evidence that circumcision protected against any STI (OR= 0.91; 95% CI, 0.83-1.00), an effect which became apparent in studies published after 2013.

Analysis of specific STIs showed that circumcision reduced the odds of HSV infection (OR = 0.84; 95% CI, 0.75-0.95) and penile HPV for MSM with HIV (OR = 0.71; 95% CI, 0.51-0.99).

The investigators suggest that stigma and discrimination would means that it is impossible to conducted a randomised controlled circumcision trial in low- and middle-income countries involving only MSM. However, they suggest that rigorously collected longitudinal data could help confirm the findings of their meta-analysis and also show if MSM would be willing to be circumcised to protect them against HIV – some research suggests that uptake would be low.

“MSM should not be excluded from campaigns promoting circumcision among men in countries of low- and middle-income,” conclude the authors. “Mathematical modelling studies should be developed to assess the public health effect and cost-effectiveness of large-scale circumcision programmes for HIV prevention among MSM in individual countries of low and middle income.” The investigators emphasise the MSM should also be provided with the full range of HIV prevention, care and treatment interventions, including pre-exposure prophylaxis (PrEP).

Dr Jillian Pintye and Professor Jared Baeten of the University of Washington argue in an accompanying editorial that the meta-analysis provides compelling evidence “that voluntary male circumcision could be an effective strategy to curb the HIV epidemic among MSM in some of the countries most burdened by HIV.”