Abstract
Objective
The aim of this review was to evaluate the scientific evidence supporting the hypothesis that male circumcision reduces the risk of HIV infection and consequently the incidence of acquired immunodeficiency syndrome (AIDS).
Patients and Methods
We performed a literature search of the major databases (Medline, Embase, Cochrane Library, Biosis and Science Citation Index) for papers published in the period 1999 to 2008, using the terms “male circumcision”, “HIV infection” and “sexually transmitted infection,” plus the combination of the search terms “foreskin” and “HIV receptor” to identify 1,048 articles. We reviewed the abstracts to identify 278 articles meriting detailed review. This detailed review considered how well individual studies were designed and carried out, using a standard checklist to provide a systematic quality rating for individual studies. This process identified a total of 80 papers, which were rated following the level of evidence and grade of recommendation scales modified from the Oxford Center for Evidence-Based Medicine.
Results
Detailed analysis of the selected articles on male circumcision and HIV infection risk revealed the following. Systematic reviews, meta-analyses and modeling studies: there were 11 papers, 10 positive (favoring circumcision) and 1 negative; of the 10 positive studies, 4 were level 3 evidence, 5 were level 2 and 1 was level 1 evidence. Randomized controlled trials: there were 3 studies, all positive with level 1 evidence. Non-randomized cohort studies: there were 6 papers, 5 were positive (2 level 3 and 3 level 2 evidence) and 1 was negative (level 3 evidence). Casecontrol studies: there were 12 studies, 11 positive (all level 3) and 1 negative (level 3 evidence). Case series: there were 2 studies, both positive (level 3 evidence). Expert opinion: there were 34 studies, 30 positive (15 level 4, 15 level 3 evidence), 2 negative (both level 4) and 2 neutral (both level 4 evidence). Cost-effectiveness studies: there were 3 studies, all positive, all level 2 evidence. Pertinent biological studies: there were 3 studies, all positive, all level 4 evidence. The three large, exceptionally well-done randomized, controlled trials of adult male circumcision among consenting, healthy men in three African countries enrolled a total of 10,908 uncircumcised, HIV-negative adult men. The cumulative HIV infection risk estimated using intention-to-treat Kaplan-Meier analysis showed an overall rate ratio (RR) of 0.42 (95% confidence interval (CI) 0.31–0.57), corresponding to a protective effect of 58% (95% CI 43-69%). Meta-analysis of the “as-treated“ results of the three trials showed even stronger protection against HIV infection in the circumcision group (summary RR 0.35, 95% CI 0.24–0.54).
Conclusions
Rigorous analysis of the available scientific evidence clearly supports a positive recommendation that male circumcision should be actively promoted in populations at high risk of HIV infection. There is a need to provide safe male circumcision services for high-risk populations, because this is one of very few proven HIV prevention strategies. Male circumcision provides a much-needed addition to the limited HIV prevention armamentarium. The challenges to implementation must now be faced.
Similar content being viewed by others
References
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):2361–2370.
Patterson BK, Landay A, Siegel JN, Flener Z, Pessis D, Chaviano A, et al. Susceptibility to human immunodeficiency virus-1 infection of human foreskin and cervical tissue grown in explant culture. Am.J.Pathol. 2002; Sep;161(3):867–873.
Soilleux EJ, Coleman N. Expression of DC-SIGN in human foreskin may facilitate sexual transmission of HIV. J.Clin.Pathol. 2004; Jan;57(1):77–78.
McCoombe SG, Short RV. Potential HIV-1 target cells in the human penis. AIDS. 2006; Jul 13;20(11):1491–1495.
Fink AJ. A possible explanation for heterosexual male infection with AIDS. N.Engl.J.Med. 1986; Oct 30;315(18):1167.
Moses S, Nagelkerke NJ, Blanchard J. Analysis of the scientific literature on male circumcision and risk for HIV infection. Int.J.STD AIDS. 1999; Sep;10(9):626–628.
Drain PK, Halperin DT, Hughes JP, Klausner JD, Bailey RC. Male circumcision, religion and infectious diseases: An ecologic analysis of 118 developing countries. BMC Infect.Dis. 2006;6:172.
Siegfried N. Does male circumcision prevent HIV infection? PLoS Med. 2005; Nov;2(11):e393.
Weiss HA, Halperin D, Bailey RC, Hayes RJ, Schmid G, Hankins CA. Male circumcision for HIV prevention: From evidence to action? AIDS. 2008; Mar 12;22(5):567–574.
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.
Bailey RC, Moses S, Parker CB, Agot K, Maclean I, Krieger JN, et al. Male circumcision for HIV prevention in young men in Kisumu, Kenya: A randomised controlled trial. Lancet. 2007; Feb 24;369(9562):643–656.
Gray RH, Kigozi G, Serwadda D, Makumbi F, Watya S, Nalugoda F, et al. Male circumcision for HIV prevention in men in Rakai, Uganda: A randomised trial. Lancet. 2007; Feb 24;369(9562):657–666.
Van Howe RS. Circumcision and HIV infection: Review of the literature and meta-analysis. Int.J.STD AIDS. 1999; Jan;10(1):8–16.
O’Farrell N, Egger M. Circumcision in men and the prevention of HIV infection: A ‘meta-analysis’ revisited. Int.J.STD AIDS. 2000; Mar;11(3):137–142.
Siegfried N, Muller M, Volmink J, Deeks J, Egger M, Low N, et al. Male circumcision for prevention of heterosexual acquisition of HIV in men. Cochrane Database Syst.Rev. 2003;(3):CD003362.
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;3:19.
Williams BG, Lloyd Smith JO, Gouws E, Hankins C, Getz WM, Hargrove J, et al. The potential impact of male circumcision on HIV in Sub-Saharan Africa. PLoS Med. 2006; Jul;3(7):e262.
Orroth KK, Freeman EE, Bakker R, Buve A, Glynn JR, Boily MC, et al. Understanding the differences between contrasting HIV epidemics in east and west Africa: Results from a simulation model of the Four Cities Study. Sex.Transm.Infect. 2007; Aug;83Suppl 1:i5–16.
Hallett TB, Singh K, Smith JA, White RG, Abu Raddad LJ, Garnett GP. Understanding the impact of male circumcision interventions on the spread of HIV in Southern Africa. PLoS ONE. 2008;3(5):e2212.
Londish GJ, Murray JM. Significant reduction in HIV prevalence according to male circumcision intervention in sub-Saharan Africa. Int.J.Epidemiol. 2008; Dec;37(6):1246–1253.
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.
Quinn TC, Wawer MJ, Sewankambo N, Serwadda D, Li C, Wabwire Mangen F, et al. Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group. N.Engl.J.Med. 2000; Mar 30;342(13):921–929.
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):1039–1040.
Meier AS, Bukusi EA, Cohen CR, Holmes KK. Independent association of hygiene, socioeconomic status and circumcision with reduced risk of HIV infection among Kenyan men. J.Acquir.Immune Defic. Syndr. 2006; Sep;43(1):117–118.
Shaffer DN, Bautista CT, Sateren WB, Sawe FK, Kiplangat SC, Miruka AO, et al. The protective effect of circumcision on HIV incidence in rural low-risk men circumcised predominantly by traditional circumcisers in Kenya: Two-year follow-up of the Kericho HIV Cohort Study. J.Acquir.Immune Defic.Syndr. 2007; Aug 1;45(4):371–379.
Millett GA, Ding H, Lauby J, Flores S, Stueve A, Bingham T, et al. Circumcision status and HIV infection among Black and Latino men who have sex with men in 3 US cities. J.Acquir.Immune Defic.Syndr. 2007; Dec 15;46(5):643–650.
Auvert B, Buve A, Ferry B, Carael M, Morison L, Lagarde E, et al. Ecological and individual level analysis of risk factors for HIV infection in four urban populations in sub-Saharan Africa with different levels of HIV infection. AIDS. 2001; Aug;15Suppl 4:S15–S30.
Auvert B, Buve A, Lagarde E, Kahindo M, Chege J, Rutenberg N, et al. Male circumcision and HIV infection in four cities in sub-Saharan Africa. AIDS. 2001; Aug;15Suppl 4:S31–S40.
MacDonald KS, Malonza I, Chen DK, Nagelkerke NJ, Nasio JM, Ndinya Achola J, et al. Vitamin A and risk of HIV-1 seroconversion among Kenyan men with genital ulcers. AIDS. 2001; Mar 30;15(5):635–639.
Gray R, Azire J, Serwadda D, Kiwanuka N, Kigozi G, Kiddugavu M, et al. Male circumcision and the risk of sexually transmitted infections and HIV in Rakai, Uganda. AIDS. 2004; Dec 3;18(18):2428–2430.
Agot KE, Ndinya Achola JO, Kreiss JK, Weiss NS. Risk of HIV-1 in rural Kenya: A comparison of circumcised and uncircumcised men. Epidemiology. 2004; Mar;15(2):157–163.
Jewkes R, Dunkle K, Nduna M, Levin J, Jama N, Khuzwayo N, et al. Factors associated with HIV sero-positivity in young, rural South African men. Int.J.Epidemiol. 2006; Dec;35(6):1455–1460.
Kapiga SH, Sam NE, Mlay J, Aboud S, Ballard RC, Shao JF, et al. The epidemiology of HIV-1 infection in northern Tanzania: Results from a community-based study. AIDS Care. 2006; May;18(4):379–387.
Johnson K, Way A. Risk factors for HIV infection in a national adult population: Evidence from the 2003 Kenya Demographic and Health Survey. J.Acquir. Immune Defic.Syndr. 2006; Aug 15;42(5):627–636.
Talukdar A, Khandokar MR, Bandopadhyay SK, Detels R. Risk of HIV infection but not other sexually transmitted diseases is lower among homeless Muslim men in Kolkata. AIDS. 2007; Oct 18;21(16):2231–2235.
Mishra V, Assche SB, Greener R, Vaessen M, Hong R, Ghys PD, et al. HIV infection does not disproportionately affect the poorer in sub-Saharan Africa. AIDS. 2007; Nov;21Suppl 7:S17–S28.
Klavs I, Hamers FF. Male circumcision in Slovenia: Results from a national probability sample survey. Sex. Transm.Infect. 2008; Feb;84(1):49–50.
Foglia G, Sateren WB, Renzullo PO, Bautista CT, Langat L, Wasunna MK, et al. High prevalence of HIV infection among rural tea plantation residents in Kericho, Kenya. Epidemiol.Infect. 2008; May;136(5):694–702.
Mermin J, Musinguzi J, Opio A, Kirungi W, Ekwaru JP, Hladik W, et al. Risk factors for recent HIV infection in Uganda. JAMA. 2008; Aug 6;300(5):540–549.
Halperin DT, Fritz K, McFarland W, Woelk G. Acceptability of adult male circumcision for sexually transmitted disease and HIV prevention in Zimbabwe. Sex.Transm.Dis. 2005; Apr;32(4):238–239.
Buchbinder SP, Vittinghoff E, Heagerty PJ, Celum CL, Seage GR,3rd, Judson FN, et al. Sexual risk, nitrite inhalant use and lack of circumcision associated with HIV seroconversion in men who have sex with men in the United States. J.Acquir.Immune Defic.Syndr. 2005; May 1;39(1):82–89.
Halperin DT, Bailey RC. Male circumcision and HIV infection: 10 years and counting. Lancet. 1999; Nov 20;354(9192):1813–1815.
Harrison DC. Male circumcision and HIV infection. Lancet. 2000; Mar 11;355(9207):926; author reply 927.
Szabo R, Short RV. How does male circumcision protect against HIV infection? BMJ. 2000; Jun 10;320(7249):1592–1594.
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; Feb;14(1):71–75.
Lerman SE, Liao JC. Neonatal circumcision. Pediatr. Clin.North Am. 2001; Dec;48(6):1539–1557.
Shapiro RL. Drawing lines in the sand: The boundaries of the HIV pandemic in perspective. Soc.Sci.Med. 2002; Dec;55(12):2189–2191.
Gisselquist D, Potterat JJ, Brody S. Running on empty: Sexual co-factors are insufficient to fuel Africa’s turbocharged HIV epidemic. Int.J.STD AIDS. 2004; Jul;15(7):442–452.
Sahasrabuddhe VV, Vermund SH. The future of HIV prevention: Control of sexually transmitted infections and circumcision interventions. Infect.Dis.Clin.North Am. 2007; Mar;21(1):241,57, xi.
Short RV. The HIV/AIDS pandemic: New ways of preventing infection in men. Reprod.Fertil.Dev. 2004;16(5):555–559.
Short RV. New ways of preventing HIV infection: Thinking simply, simply thinking. Philos.Trans.R.Soc. Lond.B.Biol.Sci. 2006; May 29;361(1469):811–820.
Nyindo M. Complementary factors contributing to the rapid spread of HIV-I in sub-Saharan Africa: A review. East Afr.Med.J. 2005; Jan;82(1):40–46.
Inungu J, MaloneBeach E, Betts J. Male circumcision and the risk of HIV infection. AIDS Read. 2005; Mar;15(3):130,1, 135, 138.
Jones R, Gazzard B, Halima Y. Preventing HIV infection. BMJ. 2005; Dec 3;331(7528):1285–1286.
Flynn P, Havens P, Brady M, Emmanuel P, Read J, Hoyt L, et al. Male circumcision for prevention of HIV and other sexually transmitted diseases. Pediatrics. 2007; Apr;119(4):821–822.
Van Howe RS, Svoboda JS, Hodges FM. HIV infection and circumcision: Cutting through the hyperbole. J.R.Soc.Health. 2005; Nov;125(6):259–265.
Auerbach JD, Hayes RJ, Kandathil SM. Overview of effective and promising interventions to prevent HIV infection. World Health.Organ.Tech.Rep.Ser. 2006; 938: 43–78; discussion:317–341.
Chan DJ. Fatal attraction: Sex, sexually transmitted infections and HIV-1. Int.J.STD AIDS. 2006; Oct;17(10):643–651.
Mboto CI, Davies A, Fielder M, Jewell AP. Human immunodeficiency virus and hepatitis C co-infection in sub-Saharan West Africa. Br.J.Biomed.Sci. 2006;63(1):29–37.
Isiugo Abanihe UC. Sociocultural aspects of HIV/AIDS infection in Nigeria. Afr.J.Med.Med.Sci. 2006; Dec;35Suppl:45–55.
Weiss HA. Male circumcision as a preventive measure against HIV and other sexually transmitted diseases. Curr.Opin.Infect.Dis. 2007; Feb;20(1):66–72.
Sawires SR, Dworkin SL, Fiamma A, Peacock D, Szekeres G, Coates TJ. Male circumcision and HIV/AIDS: Challenges and opportunities. Lancet. 2007; Feb 24;369(9562):708–713.
Schenker I, Gross E. [Male circumcision and HIV/AIDS: Convincing evidence and their implication for the state of Israel]. Harefuah. 2007; Dec;146(12):957,63, 997.
Sharp M. 14th annual retrovirus conference (CROI). HIV prevention update. Some bad news, some good news. Posit.Aware. 2007; May–Jun;18(3):26–27.
Quinn TC. Circumcision and HIV transmission. Curr. Opin.Infect.Dis. 2007; Feb;20(1):33–38.
Schoen EJ. Should newborns be circumcised? Yes. Can. Fam.Physician. 2007; Dec;53(12):2096,8, 2100-2.
Clark PA, Eisenman J, Szapor S. Mandatory neonatal male circumcision in Sub-Saharan Africa: Medical and ethical analysis. Med.Sci.Monit. 2007; Dec;13(12):RA205–RA213.
Clark S. Male circumcision could help protect against HIV infection. Lancet. 2000; Jul 15;356(9225):225.
Morris BJ. Why circumcision is a biomedical imperative for the 21(st) century. Bioessays. 2007; Nov;29(11):1147–1158.
Mor Z, Kent CK, Kohn RP, Klausner JD. Declining rates in male circumcision amidst increasing evidence of its public health benefit. PLoS ONE. 2007;2(9):e861.
Jayasuriya A, Robertson C, Allan PS. Twenty-five years of HIV management. J.R.Soc.Med. 2007; Aug;100(8):363–366.
Landovitz RJ. Recent efforts in biomedical prevention of HIV. Top.HIV.Med. 2007; Jun–Jul;15(3):99–103.
Vardi A, Guy L, Boiteux JP. Circoncision et VIH. [Circumcision and HIV]. Prog.Urol. 2008; Jun;18(6):331–336.
Cohen MS, Hellmann N, Levy JA, DeCock K, Lange J. The spread, treatment, and prevention of HIV-1: Evolution of a global pandemic. J.Clin.Invest. 2008; Apr;118(4):1244–1254.
Gray RH, Wawer MJ, Polis CB, Kigozi G, Serwadda D. Male circumcision and prevention of HIV and sexually transmitted infections. Curr.Infect.Dis.Rep. 2008; May;10(2):121–127.
Potts M, Halperin DT, Kirby D, Swidler A, Marseille E, Klausner JD, et al. Public health. Reassessing HIV prevention. Science. 2008; May 9;320(5877):749–750.
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.
Gray RH, Li X, Kigozi G, Serwadda D, Nalugoda F, Watya S, et al. 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.
Fieno JV. Costing adult male circumcision in high HIV prevalence, low circumcision rate countries. AIDS Care. 2008; May;20(5):515–520.
Krieger JN, Bailey RC, Opeya J, Ayieko B, Opiyo F, Agot K, et al. Adult male circumcision: Results of a standardized procedure in Kisumu District, Kenya. BJU Int. 2005; Nov;96(7):1109–1113.
Krieger JN, Bailey RC, Opeya JC, Ayieko BO, Opiyo FA, Omondi D, et al. Adult male circumcision outcomes: Experience in a developing country setting. Urol.Int. 2007;78(3):235–240.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Krieger, J.N., Heyns, C.F. Male circumcision and HIV/AIDS risk — Analysis of the scientific evidence. Afr J Urol 15, 76–83 (2009). https://doi.org/10.1007/s12301-009-0021-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12301-009-0021-8