HIV This Week

Desai K, Boily MC, Garnett GP, Masse BR, Moses S, Bailey RC. The role of sexually transmitted infections in male circumcision effectiveness against HIV - Insights from clinical trial simulation. Emerg Themes Epidemiol 2006;3(1):19. http://www.ete-online.com/content/3/1/19

A landmark randomised trial of male circumcision in Orange Farm, South Africa recently showed a large and significant reduction in risk of HIV infection, reporting male circumcision effectiveness of 61% (95% CI 34-77%). Additionally, two further randomised trials of male circumcision in Kisumu, Kenya and Rakai, Uganda were recently stopped early reporting 53% and 48% effectiveness, respectively. Since male circumcision may protect against both HIV and certain sexually transmitted infections (STI), which are themselves cofactors of HIV infection, an important question is the extent to which this estimated effectiveness against HIV is mediated by the protective effect of circumcision against STI. The answer lies in the trial data if the appropriate statistical analyses can be identified to estimate the separate efficacies against HIV and STI, which combine to determine overall effectiveness. Focusing on the male circumcision trial in Kisumu, Desai and colleagues used a stochastic prevention trial simulator (1) to determine whether statistical analyses can validly estimate efficacy, (2) to determine whether male circumcision efficacy against STI alone can produce large effectiveness against HIV and (3) to estimate the fraction of all HIV infections prevented that are attributable to efficacy against STI when both efficacies combine. Valid estimation of separate efficacies against HIV and STI as well as male circumcision effectiveness is feasible with available STI and HIV trial data, under Kisumu trial conditions. Under their parameter assumptions, high overall effectiveness of male circumcision against HIV was observed only with a high male circumcision efficacy against HIV and was not possible on the basis of male circumcision efficacy against STI alone. The fraction of all HIV infections prevented which were attributable to male circumcision efficacy against STI was small, except when efficacy of male circumcision specifically against HIV was very low. In the three male circumcision trials which reported between 48% and 61% effectiveness, the fraction of HIV infections prevented in circumcised males which were attributable to STI was unlikely to be more than 10% to 20%. The authors conclude that estimation of the efficacy, attributable fraction and effectiveness leads to improved understanding of trial results, gives trial results greater external validity and is essential to determine the broader public health impact of circumcision to men and women.

Editors’ note: Now that these trials have been stopped it will be possible to examine the real data on incident STI and attempt to better tease out the contribution of STI prevention to the reduced incidence of HIV seen in men who underwent circumcision in the trials. WHO/UNAIDS are hosting a global consultation on the policy and programming implications of the three circumcision trial findings for countries in March 2007 which will take a closer look at all available data from the trials.

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Kahn JG, Marseille E, Auvert B. Cost-effectiveness of male circumcision for HIV prevention in a South African setting. PLoS Med 2006;3(12):e517. 10.1371/journal.pmed.0030517

Consistent with observational studies, a randomized controlled intervention trial of adult male circumcision conducted in the general population in Orange Farm (Gauteng Province, South Africa) demonstrated a protective effect against HIV acquisition of 60%. Kahn and colleagues present the first cost-effectiveness analysis of the use of male circumcision as an intervention to reduce the spread of HIV in sub-Saharan Africa. Cost-effectiveness was modelled for 1,000 male circumcisions done within a general adult male population. Intervention costs included performing male circumcision and treatment of adverse events. HIV prevalence was estimated from published estimates and incidence among susceptible subjects calculated assuming a steady-state epidemic. Effectiveness was defined as the number of HIV infections averted, which was estimated by dynamically projecting over 20 years the reduction in HIV incidence observed in the Orange Farm trial, including secondary transmission to women. Net savings were calculated with adjustment for the averted lifetime duration cost of HIV treatment. Sensitivity analyses examined the effects of input uncertainty and programme coverage. All results were discounted to the present at 3% per year. For Gauteng Province, assuming full coverage of the male circumcision intervention, with a 2005 adult male prevalence of 25.6%, 1000 circumcisions would avert an estimated 308 (80% CI 189-428) infections over 20 years. The cost is $US 181 (80% CI 117-306) per HIV infection averted, and net savings are $US 2.4 million (80% CI 1.3 million to 3.6 million). Cost-effectiveness is sensitive to the costs of male circumcision and of averted HIV treatment, the protective effect of male circumcision, and HIV prevalence. With an HIV prevalence of 8.4%, the cost per HIV infection averted is $US 551 (80% CI 344-1071) and net savings are $US 753,000 (80% CI 0.3 million to 1.2 million). Cost-effectiveness improves by less than 10% when male circumcision intervention coverage is 50% of full coverage. The authors conclude that in settings in sub-Saharan Africa with high or moderate HIV prevalence among the general population, adult male circumcision is likely to be a cost-effective HIV prevention strategy, even when it has a low coverage. Male circumcision generates large net savings after adjustment for averted HIV medical costs.

Editors’ note: Cost per case of HIV infection averted will vary widely by setting and by the costs included in the analysis. It is important to include not just the immediate cost of the procedure and care of any adverse events (care provider, costs of equipment and supplies, facility time, etc.) but also in-service training costs, medical/clinical officer/nursing education costs, as well as individual counselling and public education on the benefits and limitations of male circumcision as an HIV prevention measure. The actual service delivery model also has implications for costs. For example, using an ‘eye camp’ service delivery model will incur quite different costs than a model which contextualises male circumcision within a programme addressing male sexual and reproductive health.