Amidst the excitement about HPTN 052 at the Rome IAS meeting, the results of the ANRS Orange Farm circumcision programme received little publicity, despite stunning data.
Orange Farm was the site of the first of three randomised control trials that showed that circumcision reduces the risk of men contracting HIV in a predominantly heterosexual population. Following the trial, the researchers implemented a scaled up circumcision programme in Orange Farm. Bertran Auvert presented a late-breaker describing the results of this programme. 
There are several important findings from this study:
- Post-trial uptake was large. Orange Farm has now carried out approximately 25,000 circumcisions.
- No deaths or permanent injuries have occurred due to circumcision. There have been ten hospitalisations and in all these cases the adverse events were resolved.
- The benefit of circumcision on HIV incidence is durable.
- There was no evidence that incidence was affected by risk compensation.
Orange Farm is a township of about 110,000 adults about 45kms from Johannesburg. Since January 2008, free voluntary medical male circumcision to all boys and men older than 15 has been offered by the ANRS-sponsored project. The intervention includes community mobilisation and outreach, counselling, condom distribution, STI treatment, HIV voluntary counselling and testing and ART if eligible.
A baseline cross-sectional survey was done in 2007. This was a random sample of just under 1,200 males aged 15 to 49 years. The response rate was 74%. Male circumcision status was determined by genital examination. A second cross-sectional survey was done in 2010. It was almost the same size and the response rate was 88%. This survey included a background and sexual behaviour questionaire. Again male circumcision status was determined by genital examination. Blood samples were tested for HIV, ARVs and for recent infection (within 6 months) using a population incidence detuned HIV test (Calypte EIA BED).
Male circumcision prevalence changed from 15.6% (95%CI: 13.6%-17.8%) of 15-49 year-olds in 2007 to 49.4% (95%CI: 46.5%-52.3%) in 2010. Using this data, the researchers calculated uptake, which increased across all age groups in the 2008-2010 period. In 15-49 year-olds it was 40% (95%CI: 38.0% to 43.5%) and 49.1% in 20 to 24 year-olds (95%CI: 42.1% to 52.4%). This substantial increase led Auvert to comment, “We are changing the social norms.”
In a comparison of 590 circumcised versus 605 uncircumcised men, circumcised men were younger, more educated, less likely to be married and more often aware of their HIV status. No difference in sexual behaviour was detected. For example reported condom usage was consistent (adjusted OR: 0.84; 95%CI: 0.63-1.1; p=0.26).
HIV prevalence and incidence
Among 586 uncircumcised men in the survey, 117 were HIV-positive (20%; 95%CI: 16.7%-23.2%). Among circumcised men, 36 out of 582 men were HIV-positive (6.2%; 95%CI: 4.3%-8.2%). This is a 55% reduction (95%CI: 39% to 70%).
In the 15-34 age group, the BED assay indicated that incidence in uncircumcised men was 3.7 per 100 person-years (95%CI: 2.2-6.1) and 0.6 per 100 person-years in circumcised men (0.19-1.9). The adjusted relative risk was 0.24 (95%CI: 0-0.66). Interestingly, this is equivalent to a 76% reduction that is exactly what the as-treated effect of the Orange Farm randomised control trial was.
Because of problems with the BED assay, a modelling exercise was also done in which HIV incidence was calculated from HIV prevalence data to determine the effect of circumcision on incidence. In this separate analysis the reduction in incidence was 83% (95%CI: 64%-98%) in 15-34 year-olds, consistent with the BED-based estimate.
It was estimated that without male circumcision, HIV prevalence would have been 25.1% higher in 15-49 year-olds in Orange Farm (95%CI: 13.1%-39.1%) and HIV incidence would have been 57.9% higher (95%CI: 17.0%-131%).
The key limitation to a study like this is that it is observational. But randomised controlled trials have already proven the efficacy of circumcision. This was the first prospective study to show the benefits of circumcision in a real-world operational setting.
A widely expressed concern about circumcision is that risk compensation would undo much of its benefit. The finding that the operational effect of circumcision matched the as-treated effect of the Orange Farm clinical trial addresses this concern. The lack of difference in reported condom usage also indicates that risk compensation is not a factor, but this must be discounted against the fact that survey participants give answers that they believe are consistent with societal expectations rather than what they actually do.
There should be no further objections to scaling up voluntary medical male circumcision in appropriately equipped facilities. The South African Department of Health has committed to scaling up circumcision and implementation is taking place in several provinces. PEPFAR and the Gates Foundation have both committed to funding circumcision programmes across sub-Saharan Africa. However South African guidelines have still not been published, albeit that a draft exists. These guidelines need to be finalised and published. An implementation plan also needs to be devised.
The Orange Farm researchers hope soon to be able to do an analysis of the effect of medical male circumcision on incidence in women.
Auvert B. 2011. Effect of the Orange Farm (South Africa) male circumcision roll-out (ANRS-12126) on the spread of HIV. 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention. 17-20 July 2011, Rome, Italy.
Thank you to Bertran Auvert, Dino Rech and Dirk Taljaard for assisting my understanding of this study.
Declaration of interest: Nathan Geffen am a member of the Orange Farm circumcision scientific committee.
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