Date Published: September 8, 2009
Publisher: Public Library of Science
Abstract: Experts from UNAIDS, WHO, and the South African Centre for Epidemiological Modelling report their review of mathematical models estimating the impact of male circumcision on HIV incidence in high HIV prevalence settings
Partial Text: Three recent randomised controlled trials – in Kenya, South Africa, and Uganda have confirmed previous observational studies  and ecological experience  and demonstrated beyond reasonable doubt that male circumcision performed by well-trained medical professionals reduces the risk of men acquiring HIV through female-to-male transmission by approximately 60% ,. Furthermore, results from the Kenyan trial indicate that the protective effects of circumcision are sustained for at least 42 mo , which suggests that circumcision is likely to provide life-long partial protection.
At the 2008 meeting, the expert group reviewed the following mathematical models for the effects of male circumcision on HIV incidence and prevalence:
Before its third meeting, the expert group identified eight key questions with implications for policy and programmatic decision-making. They then considered the findings from the models relevant to each of the questions in turn at the meeting. Not all of the models addressed all of the topics. Furthermore, in many cases, the quantitative outputs from the models could not be directly compared because alternative underlying assumptions had been made and their results related to different contexts. For this reason, the expert group did not attempt to quantify the variation in model results formally even though each of the published articles contained an analysis of the uncertainty in the relevant model’s projections.
The expected impact of scaling up male circumcision services depends on several critical factors including baseline male circumcision and HIV prevalence; whether HIV incidence is increasing, stable, or declining; the time period of model projections; and the speed of scale-up.
As sexual partners and parents, women are affected by male circumcision ,. Although an observational study suggested that circumcision of HIV-positive men might reduce transmission to HIV-negative female partners , no such direct effect was observed in a trial that was prematurely closed for futility . However, among those couples who resumed sexual activity soon after circumcision a nonstatistically significant but nonetheless concerning trend was found in this trial toward an increased risk of HIV infection in women assessed 6 mo after their partners’ circumcision.
WHO/UNAIDS advise against promoting male circumcision for HIV-positive men, but state that it should not be denied unless medically contraindicated . HIV testing is recommended for all men seeking male circumcision, but is not mandatory . The systematic refusal to circumcise HIV-positive men based on their HIV status alone may increase stigma for all uncircumcised men.
As observed with antiretroviral treatment, a decrease in perceived risk can result in an increase in sexual risk-taking behaviour, a phenomenon termed “risk compensation” ,,. The randomised trials of male circumcision ,, and an observational study  found minimal or no behavioural risk compensation among recently circumcised men, although intensive health education during the trials might have mitigated risk compensation.
It is clear that a scale-up of male circumcision that prioritises the treatment of subgroups of heterosexual men at the highest risk of HIV exposure will have the most rapid initial impact. These subgroups vary by country but include seronegative men in discordant couples identified during couple counselling and testing, STD clinic attendees, and adult males 15–34 y old. In many settings HIV incidence is highest among 25- to 34-y-old men  rather than 15- to 24-y-olds. Because changes may occur over time, HIV incidence monitoring in relevant subpopulations is essential to ensure that priority groups continue to be accurately identified.
All the models showed that rapid expansion of male circumcision coverage will result in earlier and larger effects on HIV incidence (Figure 1), assuming that safety standards and the quality of counselling and postoperative care are maintained. The models showed that whether scale-up rates are constant, faster initially then slowing, or slower initially with subsequent acceleration, they can still achieve a specified goal by the target date. However, studies in Lesotho, Swaziland, and Zambia found that a faster initial scale-up would avert between 13.7% and 16.1% more infections by 2015 compared to a linear scale-up, whereas a slower initial scale-up would result in −19.7% to −14.5% fewer infections averted, assuming a target coverage in each country of around 50% by 2015 . Thus, the expert group concluded from both the models and empirical data that rapid initial scale-up accrues direct and indirect effects earlier and is considerably more cost-effective, with fewer circumcisions required to avert one infection and more HIV infections averted at lower cost per infection averted over time.
The introduction or expansion of male circumcision services will occur in settings where behavioural prevention programmes (e.g., campaigns to increase male and female condom use or to reduce numbers of sexual partners) and biomedical measures (e.g., antiretroviral treatment) may be reducing sexual HIV transmission. Unlike other HIV prevention strategies that depend on user-adherence, male circumcision, once performed, is likely to provide lifelong partial protection against HIV, on the basis of the available evidence. Furthermore, the scale-up of male circumcision to reduce HIV incidence provides an opportunity to enhance other prevention strategies such as counselling to reduce risky behaviours, to increase correct and consistent male and female condom use, and to encourage knowledge of HIV serostatus.
The estimated costs per adult male circumcision are between $30 and $60  depending on the programme setting, with neonatal circumcision costing about one-third this amount. The models estimate costs per infection averted of between $150 and $900 in high HIV prevalence settings over a 10-y time horizon, and $100 to $400 when including infections averted to 20 y. All the models indirectly confirmed that the most favourable cost-effectiveness ratios will be seen where HIV incidence is highest. By comparison, estimates of discounted lifetime treatment costs typically exceed $7,000 per HIV infection if only first-line treatment is provided, and twice as much if second-line treatment is available . This estimate assumes first line antiretroviral treatment costs of $300 per patient per year rising to $500 by 2015, laboratory and service delivery costs of $300 per patient per year, survival of 85% in the first year after treatment initiation and 95% in subsequent years, and 3% discount rate. Thus, circumcising sexually active males of any age is likely to be cost saving ,.
To assist countries in scaling up safe, voluntary male circumcision services, WHO, UNAIDS, and partners have produced extensive guidance and several useful tools. For example, they have produced human rights guidance, a situational analysis toolkit, a communications framework, a surgical manual and training modules, a legal and regulatory self-assessment tool, and a monitoring and evaluation tool.