Gray RH, Li X, Kigozi G, Serwadda D, Nalugoda F, Watya S, Reynolds SJ, Wawer M. The Impact of Male Circumcision on HIV Incidence and Cost per Infection Prevented: A Stochastic Simulation Model from Rakai, Uganda. AIDS. 2007 Apr 23;21(7):845-850.
To estimate, through modeling, the potential public health impact of male circumcision on HIV incidence, and the number of procedures and cost per HIV infection averted.
Based on data from a cohort in Rakai, Uganda, a stochastic simulation model with empirically derived parameters was used to estimate the population-level incidence of HIV as a function of the efficacy of male circumcision.
The parameters used in the model were derived from empirical studies in Rakai, Uganda, which has a mature generalized epidemic (HIV prevalence of 11%) and an HIV incidence of 1.24/100 person-years.
The probability of HIV transmission per sex act was computed for males and females of the following ages: 15-24, 25-29, 30-34, and 35+ years. Gender-specific rates of partner change were based on data from the Rakai cohort, in which approximately 8% of HIV-infected women and 53% of HIV-infected men reported multiple partnerships in a given year.(1) In Rakai, 84% of men are uncircumcised.
To estimate the effect of circumcision performed among HIV-negative males (≥15 years old), it was assumed that circumcision reduces HIV acquisition by an incidence rate ratio (IRR) of 0.3 to 0.6 in men, female partners, and both sexes combined. An IRR of 0.7 for reduction in acquisition by women was also used. The model assumed 0-100% program coverage of HIV-negative uncircumcised men, and a cost per circumcision of USD $69, including post-operative care. The model simulated HIV transmission from an HIV-positive to an HIV-negative partner, and computed the probability of transmission per sex act by stage of HIV disease, age, and gender.
Estimates were used to calculate the cost and number of procedures required per HIV infection averted over a 10-year period. The epidemic reproductive number (R0) was estimated. To account for behavioral disinhibition, estimates were derived for increasing numbers of sexual partners per individual (by 25%, 50% or 100%).
The number of surgeries per infection averted over 10 years was estimated to range from 19 to 58; the cost per infection averted was USD $1269-3911, depending on the efficacy of circumcision and assuming 75% service coverage. A reduction in acquisition among men required efficacy of circumcision to be ≥60% (an IRR of 0.4 or less). At all levels of assumed efficacy and program coverage, the reduction in HIV acquisition among women was slightly more than acquisition among men. With >60% efficacy and 100% program coverage, circumcision could reduce incidence sufficiently to interrupt the epidemic. However, behavioral disinhibition could offset any benefits.
Based on this model, the authors suggest that male circumcision could have a substantial impact on HIV incidence in the general population, to a point where the reproductive number would decline to <1.0 and the epidemic would wane. Thus, circumcision could be a cost-effective prevention strategy if benefits are not countered by behavioral disinhibition. If the protective effect of circumcision is long-lasting,(2) male circumcision would be more cost-effective than other preventive strategies, such as nevirapine for prevention of mother-to-child HIV transmission.(3)
There are no widely accepted quality-scoring tools available for evaluating this type of simulation model. This simulation model is limited by the following factors: a. the model is based on parameters derived from empirical studies in rural Rakai, which has a mature generalized epidemic and, thus, may not apply to early rapidly expanding or high-intensity generalized epidemics, or to urban settings; b. it is questionable whether the model's assumptions about circumcision efficacy in either or both sexes are realistic.
Male circumcision has been associated with reduced risk of male HIV acquisition in several observational studies(4-8) and in one randomized trial.(9) One observational study of male-to-female HIV transmission in HIV-discordant couples has suggested that male circumcision may reduce female HIV acquisition if the infected man's viral load is
< 50,000 copies/µl.(1) A trial to assess the efficacy of male circumcision for prevention of female HIV acquisition is ongoing in Rakai, Uganda. The cost per HIV infection averted found in this study is substantially higher than that found by Kahn et al, who estimated that the cost per HIV infection averted to range from USD $181-550, depending on the HIV prevalence.(10)
Male circumcision offers the prospect of an innovative approach to HIV prevention and constitutes a unique public health intervention. However, it is impossible to know the extent to which male circumcision will impact HIV acquisition among women, and how long-lasting the effect will be. These parameters will influence the optimistic projection put forth by the authors that the HIV epidemic could be ended if circumcision coverage is widespread. If this procedure is to become a component of HIV prevention programs, high standards of surgical and post-operative care will be needed, as well as an increase in healthcare personnel capable of providing the service. Efforts will also need to address behavioral disinhibition, which might offset any benefits.
- Gray RH, Li X, Wawer MJ, Gange SJ, Serwadda D, Sewankambo NK, et al. Stochastic simulation of the impact of antiretroviral therapy and HIV vaccines on HIV transmission; Rakai, Uganda. AIDS 2003 Sep 5;17(13):1941-51.
- Kelly R, Kiwanuka N, Wawer MJ, Serwadda D, Sewankambo NK, Wabwire-Mangen F, et al. Age of male circumcision and risk of prevalent HIV infection in rural Uganda. AIDS 1999 Feb 25;13(3):399-405.
- Sweat MD, O'Reilly KR, Schmid GP, Denison J, de Zoysa I. Cost-effectiveness of nevirapine to prevent mother-to-child HIV transmission in eight African countries. AIDS 2004 Aug 20;18(12):1661-71.
- Weiss HA, Quigley MA, Hayes RJ. Male circumcision and risk of HIV infection in sub-Saharan Africa: a systematic review and meta-analysis. AIDS 2000 Oct 20;14(15):2361-70. Review.
- Gray RH, Kiwanuka N, Quinn TC, Sewankambo NK, Serwadda D, Mangen FW, et al. Male circumcision and HIV acquisition and transmission: cohort studies in Rakai, Uganda. Rakai Project Team. AIDS 2000 Oct 20;14(15):2371-81.
- Reynolds SJ, Shepherd ME, Risbud AR, Gangakhedkar RR, Brookmeyer RS, Divekar AD, et al. Male circumcision and risk of HIV-1 and other sexually transmitted infections in India. Lancet 2004 Mar 27;363(9414):1039-40.
- Lavreys L, Rakwar JP, Thompson ML, Jackson DJ, Mandaliya K, Chohan BH, et al. Effect of circumcision on incidence of human immunodeficiency virus type 1 and other sexually transmitted diseases: a prospective cohort study of trucking company employees in Kenya. J Infect Dis. 1999 Aug;180(2):330-6.
- Baeten JM, Richardson BA, Lavreys L, Rakwar JP, Mandaliya K, Bwayo JJ, et al. Female-to-male infectivity of HIV-1 among circumcised and uncircumcised Kenyan men. J Infect Dis. 2005 Feb 15;191(4):546-53. Epub 2005 Jan 18.
- Auvert B, Taljaard D, Lagarde E, Sobngwi-Tambekou J, Sitta R, Puren A. Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: the ANRS 1265 Trial. PLoS Med 2005 Nov;2(11):e298.
- Kahn JG, Marseille E, Auvert B. Cost-effectiveness of male circumcision for HIV prevention in a South African setting. PLoS Med 2006 Dec;3(12):e517.