Modelling the public health impact of male circumcision for HIV prevention in high prevalence areas in Africa

Nico J D Nagelkerke, Stephen Moses, Sake J de Vlas, Robert C Bailey, Nico J D Nagelkerke, Stephen Moses, Sake J de Vlas, Robert C Bailey

Abstract

Background: Recent clinical trials in Africa, in combination with several observational epidemiological studies, have provided evidence that male circumcision can reduce HIV female-to-male transmission risk by 60% or more. However, the public health impact of large-scale male circumcision programs for HIV prevention is unclear.

Methods: Two mathematical models were examined to explore this issue: a random mixing model and a compartmental model that distinguishes risk groups associated with sex work. In the compartmental model, two scenarios were developed, one calculating HIV transmission and prevalence in a context similar to the country of Botswana, and one similar to Nyanza Province, in western Kenya.

Results: In both models, male circumcision programs resulted in large and sustained declines in HIV prevalence over time among both men and women. Men benefited somewhat more than women, but prevalence among women was also reduced substantially. With 80% male circumcision uptake, the reductions in prevalence ranged from 45% to 67% in the two "countries", and with 50% uptake, from 25% to 41%. It would take over a decade for the intervention to reach its full effect.

Conclusion: Large-scale uptake of male circumcision services in African countries with high HIV prevalence, and where male circumcision is not now routinely practised, could lead to substantial reductions in HIV transmission and prevalence over time among both men and women.

Figures

Figure 1
Figure 1
Structure of the compartmental model. Boxes represent compartments, i.e. the states males or females can be in. Arrows represent flows of individuals between compartments. High risk groups are male clients of sex workers, and female sex workers (csw). Disease progression is subdivided into 2 stages: early and late, including AIDS. Individuals (men) move to the circumcised boxes after circumcision. The flow diagram for women is similar except that there exists no circumcised compartment. Symbols refer to compartments and flows formally defined in the Additional file 1 (Compartments: M = male, F = female; first subscript: 1 = low risk group, 2 = high risk group; second subscript: 1 = uninfected, 2 = early HIV, 3 = late HIV, 4 =circumcised and uninfected. Flows: a = from low risk to high risk group, b = from high risk to low risk group, c = circumcision, i = infection, p = progression (to late stage HIV infection), q = death)
Figure 2
Figure 2
The relationship between R0, male circumcision (MC), and sex-specific equilibrium HIV prevalence, under a random mixing assumption, assuming different levels of heterogeneity of sexual behaviour (rates of partner change). The distribution of male and female rates of partner change (x) are assumed to be Nm(x) ~Gamma(x, pm, αm) and Nf(x) ~Gamma(x, pf, αf) respectively. Bottom panel: homogeneous rates of partner change; middle panel: moderate heterogeneity in rates of partner change with parameters pm = 1 & pf = 0.5; top panel: high heterogeneity in rates of partner change with parameters pm = 0.5 & pf = 0.25. Continuous arrows indicate the approximate position of "Botswana" and the dotted arrow indicates the approximate position of "Nyanza".
Figure 3
Figure 3
The impact of male circumcision (MC) on HIV prevalence in the Botswana setting, according to our compartmental model, with high, 80%, MC uptake (bottom panel) and moderate, 50%, MC uptake (top panel). Predictions are for the period 2000–2100, when male circumcision is introduced in 2010. In addition the figure shows the results of 4 different sensitivity analyses: RR0.25: if protection afforded by circumcision would be as high 75% (RR 0.25); RR0.60: if it would be as low as 40% (RR 0.60); DISINHIB: if it would lead to disinhibition in the sense that condom use in high risk sex would be abandoned; MF 0.75: if male circumcision would reduce the risk of male-to-female transmission by 25%.
Figure 4
Figure 4
The impact of male circumcision (MC) on HIV prevalence in the Nyanza setting, according to our compartmental model, with high, 80%, MC uptake (bottom panel) and moderate, 50%, MC uptake (top panel). Predictions are for the period 2000–2100, when male circumcision is introduced in 2010. In addition the figure shows the results of 4 different sensitivity analyses:RR0.25: if protection afforded by circumcision would be as high 75% (RR 0.25); RR0.60: if it would be as low as 40% (RR 0.60); DISINHIB: if it would lead to disinhibition in the sense that condom use in high risk sex would be abandoned; MF 0.75: if male circumcision would reduce the risk of male-to-female transmission by 25%.

References

    1. UNAIDS Global Report 2006. Accessed August 12,2006.
    1. Gray RH, Li X, Wawer MJ, Gange SJ, Serwadda D, Sewankambo NK, Moore R, Wabwire-Mangen F, Lutalo T, Quinn TC, Rakai Project Group Stochastic simulation of the impact of antiretroviral therapy and HIV vaccines on HIV transmission; Rakai, Uganda. AIDS. 2003;17:1941–51. doi: 10.1097/00002030-200309050-00013.
    1. Fink AJ. A possible explanation for heterosexual male infection with AIDS [letter] N Engl J Med. 1986;315:1167.
    1. Moses S, Bradley JE, Nagelkerke NJ, Ronald AR, Ndinya-Achola JO, Plummer FA. Geographical patterns of male circumcision practices in Africa: association with HIV seroprevalence. Int J Epidemiol. 1990;19:693–7. doi: 10.1093/ije/19.3.693.
    1. Caldwell JC, Caldwell P. The African AIDS epidemic. Sci Am. 1996;274:62–3. 66-8.
    1. Bongaarts J, Reining P, Way P, Conant F. The relationship between male circumcision and HIV infection in African populations. AIDS. 1989;3:373–7. doi: 10.1097/00002030-198906000-00006.
    1. Quigley MA, Weiss HA, Hayes RJ. Male circumcision as a measure to control HIV infection and other sexually transmitted diseases. Curr Opin Infect Dis. 2001;14:71–5. doi: 10.1097/00001432-200102000-00012.
    1. Siegfried N, Muller M, Volmink J, Deeks J, Egger M, Low N, Weiss H, Walker S, Williamson P. Male circumcision for prevention of heterosexual acquisition of HIV in men. Cochrane Database Syst Rev. 2003;3:CD003362.
    1. 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;2:e298. doi: 10.1371/journal.pmed.0020298.
    1. Cassell MM, Halperin DT, Shelton JD, Stanton D. Riskcompensation: the Achilles' heel of innovations in HIV prevention? BMJ. 2006;332:605–7. doi: 10.1136/bmj.332.7541.605.
    1. Accessed December 18, 2005.
    1. Krieger JN, Bailey RC, Opeya J, Ayieko B, Opiyo F, Agot K, Parker C, Ndinya-Achola JO, Magoha GA, Moses S. Adult male circumcision: results of a standardized procedure in Kisumu District, Kenya. BJU Int. 2005;96:1109–13. doi: 10.1111/j.1464-410X.2005.05810.x.
    1. Bailey RC, Moses S, Parker CB, Agot K, Maclean I, Krieger JN, Williams CF, Campbell RT, Ndinya-Achola JO. Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomised controlled trial. Lancet. 2007;369:643–56. doi: 10.1016/S0140-6736(07)60312-2.
    1. Accessed December 18, 2005.
    1. Gray RH, Kigozi G, Serwadda D, Makumbi F, Watya S, Nalugoda F, Kiwanuka N, Moulton LH, Chaudhary MA, Chen MZ, Sewankambo NK, Wabwire-Mangen F, Bacon MC, Williams CF, Opendi P, Reynolds SJ, Laeyendecker O, Quinn TC, Wawer MJ. Male circumcision for HIV prevention in men inRakai, Uganda: a randomised trial. Lancet. 2007;369:657–66. doi: 10.1016/S0140-6736(07)60313-4.
    1. Circumcision reduces HIV rates US studies confirm Accessed December 18, 2006.
    1. Accessed December 18,2006.
    1. Gray RH, Kiwanuka N, Quinn TC, Sewankambo NK, Serwadda D, Mangen FW, Lutalo T, Nalugoda F, Kelly R, Meehan M, Chen MZ, Li C, Wawer MJ. Male circumcision and HIV acquisition and transmission: cohort studies in Rakai, Uganda. Rakai Project Team. AIDS. 2000;14:2371–81. doi: 10.1097/00002030-200010200-00019.
    1. Gray R, Wawer M, Thoma M, Serwadda D, Nalugoda F, Li X, Kigozi G, Kiwanuka N, Laeyendecker O, Quinn ThomasC. Male circumcision and the risks of female HIV and sexually transmitted infections acquisition in Rakai, Uganda. Thirteenth Conference on Retroviruses and Opportunistic Infections, Denver, abstract 128. 2006.
    1. Van Howe RS, Svoboda JS, Hodges FM. HIV infection and circumcision: cutting through the hyperbole. J R Soc Health. 2005;125:259–65.
    1. Williams BG, Lloyd-Smith JO, Gouws E, Hankins C, Getz WM, Hargrove J, de Zoysa I, Dye C, Auvert B. The Potential Impact of Male Circumcision on HIV in Sub-Saharan Africa. PLoS Med. 3:e262. doi: 10.1371/journal.pmed.0030262. 2006 Jul 11.
    1. Nagelkerke NJ, Jha P, de Vlas SJ, Korenromp EL, Moses S, Blanchard JF, Plummer FA. Modelling HIV/AIDS epidemics in Botswana and India: impact of interventions to prevent transmission. Bull World Health Organ. 2002;80:89–96.
    1. May RM, Anderson RM. Transmission dynamics of HIV infection. Nature. 1987;326:137–42. doi: 10.1038/326137a0.
    1. May RM, Anderson RM. The transmission dynamics of human immunodeficiency virus (HIV) Philos Trans R Soc Lond B Biol Sci. 1988;321:565–607.
    1. Anderson RM, May RM. Infectious diseases of humans: dynamics and control. Oxford: Oxford University Press; 1991.
    1. World Bank . Confronting AIDS: public priorities in a global epidemic. New York: Oxford University Press; 1999.
    1. Dushoff J. Host heterogeneity and disease endemicity: a moment-based approach. Theor Popul Biol. 1999;56:325–335. doi: 10.1006/tpbi.1999.1428.
    1. Handcock MS, Jones JH. Likelihood-based inference for stochastic models of sexual network formation. Theor Popul Biol. 2004;65:413–22. doi: 10.1016/j.tpb.2003.09.006.
    1. Accessed December 18,2005.
    1. Glynn JR, Carael M, Auvert B, Kahindo M, Chege J, Musonda R, Kaona F, Buve A, Study Group on the Heterogeneity of HIV Epidemics in African Cities Study Group on the Heterogeneity of HIV Epidemics in African Cities. Why do young women have a much higher prevalence of HIV than young men? A study in Kisumu, Kenya and Ndola, Zambia. AIDS. 2001:S51–60. doi: 10.1097/00002030-200108004-00006.
    1. Wawer MJ, Gray RH, Sewankambo NK, Serwadda D, Li X, Laeyendecker O, Kiwanuka N, Kigozi G, Kiddugavu M, Lutalo T, Nalugoda F, Wabwire-Mangen F, Meehan MP, Quinn TC. Rates of HIV-1 transmission per coital act, by stage of HIV-1 infection, in Rakai, Uganda. J Infect Dis. 2005;191:1403–9. doi: 10.1086/429411.
    1. Anderson RM, May RM. The epidemiological parameters of HIV transmission. Nature. 1988;333:514–19. doi: 10.1038/333514a0.
    1. Accessed 21 December 2006.
    1. Nagelkerke NJD, De Vlas SJ. The epidemiological Impact of an HIV vaccine on the HIV/AIDS epidemic in Southern India World Bank Policy Research Working paper 2978 (2003)
    1. Nagelkerke N, Jha P, De Vlas S, Korenromp E, Moses S, Blanchard J, Plummer F. Modelling the HIV/AIDS epidemics in India andBotswana: The effect of interventions (2001) Commission for macroeconomics and health, WG5.
    1. Nagelkerke NJD, Arni SRS, Rao ASRS, DeVlas SJ, Marseille E. A background paper for: HIV/AIDS treatment and prevention in India: Modeling the Costs and Consequences. Washington, DC: World Bank; 2004. The projected impact of alternative policies towards ART on HIV transmission and mortality in India: a mathematical epidemiological model.
    1. Luke N. Age and economic asymmetries in the sexual relationships of adolescent girls in Sub-Saharan Africa. Studies in family planning. 2003;34:67–86. doi: 10.1111/j.1728-4465.2003.00067.x.
    1. Luke N, Kurz KM. Cross-generational and Transactional Sexual Relations in Sub-Saharan Africa. Washington: the International Center for Research on Women (ICRW); 2002.
    1. Accessed December 18,2005.
    1. Baeten JM, Richardson BA, Lavreys L, Rakwar JP, Mandaliya K, Bwayo JJ, Kreiss JK. Female-to-male infectivity of HIV-1 amongcircumcised and uncircumcised Kenyan men. J Infect Dis. 2005;191:546–53. doi: 10.1086/427656.
    1. Cowan FM, Langhaug LF, Hargrove JW, Jaffar S, Mhuriyengwe L, Swarthout TD, Peeling R, Latif A, Basset MT, Brown DW, Mabey D, Hayes RJ, Wilson D. Is sexual contact with sex workers important in driving the HIV epidemic among men in rural Zimbabwe? J Acquir Immune DeficSyndr. 2005;40:371–6. doi: 10.1097/01.qai.0000162420.93243.ff.
    1. Carael M, Slaymaker E, Lyerla R, Sarkar S. Clients of sexworkers in different regions of the world: hard to count. Sex Transm Infect. 2006;82:iii26–33. doi: 10.1136/sti.2006.021196.
    1. Elmore-Meegan M, Conroy RM, Agala CB. Sex workers inKenya, numbers of clients and associated risks: an exploratory survey. Reprod Health Matters. 2004;12:50–7. doi: 10.1016/S0968-8080(04)23125-1.
    1. Pickering H, Okongo M, Nnalusiba B, Bwanika K, Whitworth J. Sexual networks in Uganda: casual and commercial sex in a trading town. AIDS Care. 1997;9:199–207. doi: 10.1080/09540129750125217.
    1. Voeten HA, Egesah OB, Ondiege MY, Varkevisser CM, Habbema JD. Clients of female sex workers in Nyanza province, Kenya: a core group in STD/HIV transmission. Sex Transm Dis. 2002;29:444–52. doi: 10.1097/00007435-200208000-00003.
    1. Pilcher CD, Tien HC, Eron JJ, Jr, Vernazza PL, Leu SY, Stewart PW, Goh LE, Cohen MS, Quest Study; Duke-UNC-Emory Acute HIV Consortium Brief but efficient: acute HIV infection and the sexual transmission of HIV. J Infect Dis. 2004;189:1785–92. doi: 10.1086/386333.
    1. Buve A. HIV epidemics in Africa: what explains the variations in HIV prevalence? IUBMB Life. 2002;53:193–5.
    1. Plummer ML, Wight D, Ross DA, Balira R, Anemona A, Todd J, Salamba Z, Obasi AI, Grosskurth H, Changalunga J, Hayes RJ. Asking semi-literate adolescents about sexual behaviour: the validity of assisted self-completion questionnaire (ASCQ) data in rural Tanzania. Trop Med Int Health. 2004;9:737–54. doi: 10.1111/j.1365-3156.2004.01254.x.
    1. Plummer ML, Ross DA, Wight D, Changalucha J, Mshana G, Wamoyi J, Todd J, Anemona A, Mosha FF, Obasi AI, Hayes RJ. "A bit more truthful": the validity of adolescent sexual behaviour data collected in rural northern Tanzania using five methods. Sex Transm Infect. 2004;80:49–56.
    1. Accessed December 18 2005.
    1. Williams BG, Gouws E. The epidemiology of human immunodeficiency virus in South Africa. Philos Trans R Soc Lond B Biol Sci. 2001;356:1077–86.
    1. Kahn JG, Marseille E, Auvert B. XVI International AIDS conference, August 15, 2006, Toronto, Canada. [abstract #TUAC0204]
    1. Scotland GS, van Teijlingen ER, van der Pol M, Smith WC. A review of studies assessing the costs and consequences of interventions to reduce mother-to-child HIV transmission in sub-Saharan Africa. AIDS. 2003;17:1045–52. doi: 10.1097/00002030-200305020-00014.

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