Critique of African RCTs into Male Circumcision and HIV Sexual Transmission

  • Gregory J. BoyleEmail author


On the basis of three seriously flawed sub-Saharan African randomized clinical trials into female-to-male (FTM) sexual transmission of HIV, in 2007 WHO/UNAIDS recommended circumcision (MC) of millions of African men as an HIV preventive measure, despite the trials being compromised by irrational motivated reasoning, inadequate equipoise, selection bias, inadequate blinding, problematic randomization, trials stopped early with exaggerated treatment effects, and failure to investigate non-sexual transmission. Several questions remain unanswered. Why were the trials carried out in countries where more intact men were HIV+ than in those where more circumcised men were HIV+? Why were men sampled from specific ethnic subgroups? Why were so many men lost to follow-up? Why did men in the intervention group receive additional counselling on safe sex practices? The absolute reduction in HIV transmission associated with MC was only 1.3 % (without even adjusting for known sources of error bias). Relative reduction was reported as 60 %, but after correction for lead-time bias alone averaged 49 %. In a related Ugandan RCT into male-to-female (MTF) transmission, there was a 61 % relative increase (6 % absolute increase) in HIV infection among female partners of circumcised men, some of whom were not informed that their male partners were HIV+ (also some of the men were not informed by the researchers that they were HIV+). It appears that the number of circumcisions needed to infect a woman (Number Needed to Harm) was 16.7, with one woman becoming infected for every 17 circumcisions performed. As the trial was stopped early for “futility,” the increase in HIV infections was not statistically significant, although clinically significant. In the Kenyan trial, MC was associated with at least four new incident infections. Since MC diverts resources from known preventive measures and increases risk-taking behaviors, any long-term benefit in reducing HIV transmission remains dubious.


Randomized clinical trials  HIV/AIDS  Sexual transmission  Male to female transmission  Female to male transmission  Researcher bias  External validity  



The author acknowledge the assistance of George Hill, Vice-President for Bioethics and Medical Science, Doctors Opposing Circumcision, Seattle, Washington 98107, USA.


  1. Ajwang J (2007) Uganda: HIV—circumcision isn’t enough, Monitor (Kampala), 10 April.
  2. Altman D (1994) The scandal of poor medical research. BMJ 308:383–384Google Scholar
  3. Auvert B, Taljaard D, Lagarde E et al (2005) Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: the ANRS 1265 trial. PLoS Med 2(11):e2CrossRefGoogle Scholar
  4. Bailey RC, Moses S, Parker CB et al (2007) Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomised controlled trial. Lancet 369(9562):643–656PubMedCrossRefGoogle Scholar
  5. Bailey RC et al. (2010) The protective effect of adult male circumcision against HIV acquisition is sustained for at least 54 months: results from the Kisumu, Kenya trial. IAC, Abstract FRLBC101Google Scholar
  6. Bassler D, Briel M, Montori VM et al (2010) Stopping randomized trials early for benefit and estimation of treatment effects: systematic review and meta-regression analysis. JAMA 303(12):1180–1187PubMedCrossRefGoogle Scholar
  7. Bensley GA, Boyle GJ (2001) Physical, sexual, and psychological impact of male infant circumcision: an exploratory study. In: Denniston GC et al. (eds) Understanding circumcision: a multi-disciplinary approach to a multi-dimensional problem Kluwer/Plenum, NYGoogle Scholar
  8. Bensley GA, Boyle GJ (2003) Effects of male circumcision on female arousal and orgasm. New Zealand Med J 116:595–596Google Scholar
  9. Benson K, Hartz AJ (2000) A comparison of observational studies and randomized, controlled trials. N Engl J Med 342(25):1878–1886PubMedCrossRefGoogle Scholar
  10. Bernstein HB, Kinter AL, Jackson R et al (2004) Neonatal natural killer cells produce chemokines and suppress HIV replication in vitro. AIDS Res Hum Retroviruses 20(11):1189–1195PubMedGoogle Scholar
  11. Beyrer C, Trapence G, Motimedi F et al (2009) Bisexual concurrency, bisexual partnerships, and HIV among Southern African men who have sex with men (MSM). Sex Transm Infect 86(4):323–327CrossRefGoogle Scholar
  12. Boyle GJ (2003) Issues associated with the introduction of circumcision into a non-circumcising society. Sex Transm Infect 79:427–428PubMedCrossRefGoogle Scholar
  13. Boyle GJ (2004) Male circumcision and risk of HIV-1 infection. Lancet 363:1997PubMedCrossRefGoogle Scholar
  14. Boyle GJ, Hill G (2011) “The case for boosting infant male circumcision in the face of rising heterosexual transmission of HIV”…and now the case against. Med J Aust 194(2):99PubMedGoogle Scholar
  15. Boyle GJ, Svoboda JS, Price CP et al (2000) Circumcision of healthy boys: criminal assault? J Law Med 7:301–310Google Scholar
  16. Boyle GJ, Goldman R, Svoboda JS et al (2002) Male circumcision: pain, trauma and psychosexual sequelae. J Health Psychol 7:329–343PubMedGoogle Scholar
  17. Brazil says no to circumcision (2007) VivirLatino, 3 April 2007. (Retrieved Dec. 26, 2010). URL.
  18. Brewer D, Potterat JJ, Robert JM et al (2007) Male and female circumcision associated with prevalent HIV infection in virgins and adolescents in Kenya, Lesotho, and Tanzania. Ann Epidemiol 17:217–226PubMedGoogle Scholar
  19. Brody S, Potteratt JJ (2003) Assessing the role of anal intercourse in the epidemiology of AIDS in Africa. Int J STD AIDS 14:431–436PubMedCrossRefGoogle Scholar
  20. Chao A, Bulterys M, Musanganire F et al (1994) Risk factors associated with prevalent HIV-1 infection among pregnant women in Rwanda. National university of Rwanda-Johns Hopkins university AIDS research team. Int J Epidemiol 23(2):371–380PubMedCrossRefGoogle Scholar
  21. Clouser CL, Patterson SE, Mansky LM (2010) Exploiting drug repositioning for discovery of a novel HIV combination therapy. J Virol 84(18):9301–9309PubMedCrossRefGoogle Scholar
  22. Cocks T (2006) Ugandan president rejects circumcision study, Independent Online, 22 Dec, 2006. URL. (Retrieved Dec. 26, 2010)
  23. Cold CJ, Taylor JR (1999) The prepuce. BJU Int 83(Suppl. 1):34–44PubMedGoogle Scholar
  24. Concato J, Shah N, Horwitz RI (2000) Randomized, controlled trials, observational studies, and the hierarchy of research designs. N Engl J Med 342(25):1887–1892PubMedCrossRefGoogle Scholar
  25. Dowsett GW, Couch M (2007) Male circumcision and HIV prevention: is there really enough of the right kind of evidence? Reprod Health Matters 15(29):33–44PubMedCrossRefGoogle Scholar
  26. de Witte L, Nabatov A, Pion M et al (2007) Langerin is a natural barrier to HIV-1 transmission by Langerhans cells. Nat Med 13:361–371CrossRefGoogle Scholar
  27. Dekkers W (2009) Routine (non-religious) neonatal circumcision and bodily integrity: a transatlantic dialogue. Kennedy Inst Ethics J 19(2):125–146PubMedCrossRefGoogle Scholar
  28. Dekkers M, von Elm E, Algra A et al (2010) How to assess the external validity of therapeutic trials: a conceptual approach. Int J Epidemiol 39:89–94PubMedCrossRefGoogle Scholar
  29. Edwards SJL, Lilford RJ, Hewison J (1998) The ethics of randomised controlled trials from the perspectives of patients, the public, and healthcare professionals. Br Med J 317(7167):1209–1212CrossRefGoogle Scholar
  30. Fleming DT, Wasserheit JN (1999) From epidemiological synergy to public health policy and practice: the contribution of other sexually transmitted diseases to sexual transmission of HIV infection. Sex Transm Infect 75(1):3–17PubMedCrossRefGoogle Scholar
  31. Freedman B (1987) Equipoise and the ethics of clinical research. N Eng J Med 317(3):141–145CrossRefGoogle Scholar
  32. Fox M, Thomson M (2010) HIV/AIDS and circumcision: lost in translation. J Med Ethics 36:798–801PubMedCrossRefGoogle Scholar
  33. Garenne M (2006) Male circumcision and HIV control in Africa. PLoS Med 3(1):31CrossRefGoogle Scholar
  34. Garenne M (2008) Long-term population effect of male circumcision in generalised HIV epidemics in sub-Saharan Africa. Afr J AIDS Res 7(1):1–8CrossRefGoogle Scholar
  35. Giannetti M (2000) Circumcision and the American academy of pediatrics: should scientific misconduct result in trade association liability? Iowa Law Rev 85:1507–1568PubMedGoogle Scholar
  36. Gifford F (1995) Community-equipoise and the ethics of randomized clinical trials. Bioethics 9(2):127–148PubMedCrossRefGoogle Scholar
  37. Gisselquist D (2007) Points to consider: responses to HIV/AIDS in Africa, Asia, and the Caribbean. Adonis & Abbey, LondonGoogle Scholar
  38. Gisselquist D (2008) Denialism undermines AIDS prevention in sub-Saharan Africa. Int J STD AIDS 19:649–654PubMedCrossRefGoogle Scholar
  39. Gisselquist D (2009a) HIV infections as unanticipated problems during medical research in Africa. Accountability Res 16:199–217CrossRefGoogle Scholar
  40. Gisselquist D (2009b) Double standards in research ethics, health-care safety, and scientific rigour allowed Africa’s HIV/AIDS epidemic disasters. Int J STD AIDS 20(12):839–845PubMedCrossRefGoogle Scholar
  41. Gisselquist D, Rothenberg R, Potterat J et al (2002) HIV infections in sub-Saharan Africa not explained by sexual or vertical transmission. Int J STD AIDS 13:657–666PubMedCrossRefGoogle Scholar
  42. Gisselquist D, Potterat JJ, Brody S (2004) Running on empty: sexual co-factors are insufficient to fuel Africa’s turbocharged HIV epidemic. Int J STD AIDS 15:442–452PubMedCrossRefGoogle Scholar
  43. Goldman R (2004) Circumcision policy: a psychosocial perspective. Paediatr Child Health 9(9):630–633PubMedGoogle Scholar
  44. Gray RH, Kigozi G, Serwadda D et al (2007) Male circumcision for HIV prevention in men in Rakai Uganda: a randomised trial. Lancet 369(9562):657–666PubMedCrossRefGoogle Scholar
  45. Green LW, McAllister RG, Peterson KW et al (2008) Male circumcision is not the HIV ‘vaccine’ we have been waiting for! Fut HIV Ther 2(3):293–299Google Scholar
  46. Green LW, Travis JW, McAllister RG et al (2010) Male circumcision and HIV prevention: insufficient evidence and neglected external validity. Am J Prev Med 39(5):479–482PubMedCrossRefGoogle Scholar
  47. Johnson M (2010) Male genital mutilation: beyond the tolerable? Ethnicities 10(2):181–207CrossRefGoogle Scholar
  48. Karlberg JPE (2010) Personal communication (email). University of Hong Kong.Google Scholar
  49. Karlberg JPE, Speers MA (2010) Reviewing clinical trials: a guide for the ethics committee. Karlberg JPE, Hong KongGoogle Scholar
  50. Kalichman S, Eaton L, Pinkerton S (2007) Circumcision for HIV prevention: failure to fully account for behavioral risk compensation. PloS Med 4(3):e138PubMedCrossRefGoogle Scholar
  51. Karim QA, Karim SA, Frohlich JA et al (2010) Effectiveness and safety of Tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science 329(5996):1168–1174CrossRefGoogle Scholar
  52. Kim DS, Lee JY and Pang MG (1999) Male circumcision: A South Korean perspective. Brit J Urol Int 83:28Google Scholar
  53. Kunda Z (1990) The case for motivated reasoning. Psych Bull 108(3):480–498CrossRefGoogle Scholar
  54. Laumann EO, Masi CM, Zuckerman EW (1997) Circumcision in the United States: prevalence, prophylactic effects, and sexual practice. JAMA 277:1052–1057PubMedCrossRefGoogle Scholar
  55. Lie RK, Miller FG (2011) What counts as reliable evidence for public health policy: the case of circumcision for preventing HIV infection. BMC Med Res Methodol 11:34PubMedCrossRefGoogle Scholar
  56. Magoha GA (1999) Circumcision in various Nigerian and Kenyan hospitals. East Afr Med J 76: 583Google Scholar
  57. Mattson CL, Muga R, Poulussen R, Onyango T, Bailey RC (2004) Feasibility of medical male circumcision in Nyanza province. Kenya. East Afr Med J 81:320–335Google Scholar
  58. McAllister RG, Travis JW, Bollinger D et al (2008) The cost to circumcise Africa. Int J Men’s Health 7(3):307–316CrossRefGoogle Scholar
  59. Mehta SD, Gray RH, Auvert B et al (2009) Does sex in the early period after circumcision increase HIV-seroconversion risk? Pooled analysis of adult male circumcision clinical trials. AIDS 23(12):1557–1564PubMedCrossRefGoogle Scholar
  60. Mills E, Siegfried N (2006) Cautious optimism for new HIV/AIDS prevention strategies. Lancet 368:1236PubMedCrossRefGoogle Scholar
  61. Millet GA, Ding H, Lauby J et al (2007) Circumcision status and HIV infection among black and Latino men who have sex with men in three US cities. J Acquir Immune Defic Syndr 46(5):643–650CrossRefGoogle Scholar
  62. Millet GA, Flores SA, Marks G et al (2008) Circumcision status and risk of HIV and sexually transmitted infections among men who have sex with men: a meta-analysis. JAMA 300(14):1674–1684CrossRefGoogle Scholar
  63. Moher D, Hopewell S, Schulz KF et al (2010) CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. Br Med J 340:c869CrossRefGoogle Scholar
  64. Mor Z, Kent CK, Kohn RP et al (2007) Declining rates in male circumcision amidst increasing evidence of its public health benefit. PLoS ONE 2(9):e861PubMedCrossRefGoogle Scholar
  65. Montori VM, Devereaux PJ, Adhikari NK et al (2005) Randomized trials stopped early for benefit: a systematic review. JAMA 294:2203–2209PubMedCrossRefGoogle Scholar
  66. Muula AS, Prozesky HW, Mataya RH et al (2007) Prevalence of complications of male circumcision in Anglophone Africa: a systematic review. BMC Urol 7:4PubMedCrossRefGoogle Scholar
  67. Padian NS, McCoy SI, Balkus JE et al (2010) Weighing the gold in the gold standard: challenges in HIV prevention research. AIDS 24(5):621–635PubMedCrossRefGoogle Scholar
  68. Pinkerton SD (2001) Sexual risk compensation and HIV/STD transmission: empirical evidence and theoretical considerations. Risk Anal 21:727–736PubMedCrossRefGoogle Scholar
  69. Pocock S, White I (1999) Trials stopped early: too good to be true? Lancet 353:943–944PubMedCrossRefGoogle Scholar
  70. Price C (1997) Male circumcision: an ethical and legal affront. Bull Med Ethics 128:13–19PubMedGoogle Scholar
  71. Quinn TC, Wawer MJ, Sewankambo N et al (2000) Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai project study group. N Engl J Med 342(13):921–929PubMedCrossRefGoogle Scholar
  72. Raffle AE, Morgan K (1998) Financial inducements are equivalent to coercion. BMJ 316(7128):394PubMedGoogle Scholar
  73. Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S et al (2009) Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med 361(23):2209–2220PubMedCrossRefGoogle Scholar
  74. Roehr B (2010) How homophobia is fuelling Africa’s HIV epidemic. BMJ 340:c2245PubMedCrossRefGoogle Scholar
  75. Rothwell PM (2005) External validity of randomised controlled trials: “to whom do the results of this trial apply?”. Lancet 365:82–93PubMedCrossRefGoogle Scholar
  76. Sanson-Fisher RW, Bonevski B, Green LW et al (2007) Limitations of the randomized controlled trial in evaluating population-based health interventions. Am J Prev Med 33(2):155–161PubMedCrossRefGoogle Scholar
  77. Schulz KF, Chalmers I, Hayes RJ et al (1995) Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA 273:408–412PubMedCrossRefGoogle Scholar
  78. Siegfried N, Muller M, Volmink J et al. (2003) Male circumcision for prevention of heterosexual acquisition of HIV in men (Cochrane Review). In: The Cochrane Library, Issue 3, Update Software, OxfordGoogle Scholar
  79. Siegfried N, Muller M, Deeks et al (2005) HIV and male circumcision-A systematic review with assessment of the quality of studies. Lancet Infect Dis 5:165Google Scholar
  80. Siegfried N, Muller M, Deeks JJ et al. (2009) Male circumcision for prevention of heterosexual acquisition of HIV in men. Cochrane Database Syst Rev 2 (CD003362). URL:
  81. Sorrells ML, Reiss JL, Snyder MD et al (2007) Fine-touch pressure thresholds in the adult penis. BJU Int 99:864–869PubMedCrossRefGoogle Scholar
  82. Stallings RY, Karugendo E (2005) Female circumcision and HIV infection in Tanzania: for better or for worse? 3rd IAS conference HIV pathogen and treatment, Rio de Janeiro, Brazil, 24–27 JulyGoogle Scholar
  83. Statement on Kenyan and Ugandan trial findings regarding male circumcision and HIV (2006) WHO, Geneva, Switzerland, December 13. (Retrieved Oct. 15, 2010)
  84. Sussman JB, Hayward RA (2010) An IV for the RCT: using instrumental variables to adjust for treatment contamination in randomised controlled trials. BMJ 340:c2073PubMedCrossRefGoogle Scholar
  85. Taylor JR, Lockwood AP, Taylor AJ (1996) The prepuce: specialized mucosa of the penis and its loss to circumcision. Br J Urol 77:291–295PubMedCrossRefGoogle Scholar
  86. The “ABCs” of HIV prevention: report of a USAID technical meeting on behavior change approaches to primary prevention of HIV/AIDS (2002) 17 SeptGoogle Scholar
  87. Thomas AG, Bakhireva LN, Brodine SK et al. (2004) Prevalence of male circumcision and its association with HIV and sexually transmitted infections in a U.S. navy population. Abstract no. TuPeC4861. Presented at the XV international AIDS conference, Bangkok, Thailand, 11–16 July 2004Google Scholar
  88. Todd C (2001) Research participation and financial inducements. Amer J Bioethics 1(2):60–61CrossRefGoogle Scholar
  89. Urassa M, Todd J, Boerra JT et al (1997) Male circumcision and susceptibility to HIV infection among men in Tanzania. AIDS 11:73–80Google Scholar
  90. Vandenbroucke JP (2008) Observational research, randomised trials, and two views of medical science. PLoS Med 5(3):e67PubMedCrossRefGoogle Scholar
  91. Van Howe RS (2010) Analysis of the circumcision/HIV randomised clinical trials. Unpublished manuscriptGoogle Scholar
  92. Van Howe RS, Storms MR (2011) How the circumcision solution in Africa will increase HIV infections. J Pub Health Africa 2:e4. doi: 10.4081/jphia.2011.e4 Google Scholar
  93. Van Spall HG, Toren A, Kiss A et al (2007) Eligibility criteria of randomized controlled trials published in high-impact general medical journals: a systematic sampling review. JAMA 297(11):1233–1240PubMedCrossRefGoogle Scholar
  94. Vines J (2006) Major potential confounder not addressed. PLoS Med 3(1):e63PubMedCrossRefGoogle Scholar
  95. Verástegui EL (2006) Consenting of the vulnerable: the informed consent procedure in advanced cancer patients in Mexico. BMC Med Ethics 7:13CrossRefGoogle Scholar
  96. Wakabi W (2007) Homophobia is fuelling the AIDS epidemic in Africa. CMAJ 177(9):1017Google Scholar
  97. Wassenaar D (2007) Double standards in research ethics. Case-studies: informed consent and vaccine to treat rotavirus. EU forum on ethics, research and globalisation. BrusselsGoogle Scholar
  98. Wawer MJ, Makumbi F, Kigozi G et al (2009) Circumcision in HIV-infected men and its effect on HIV transmission to female partners in Rakai, Uganda: a randomised controlled trial. Lancet 374:229–237PubMedCrossRefGoogle Scholar
  99. Weinstein RS, Weinstein MM, Alibek K et al (2010) Significantly reduced CCR5-tropic HIV-1 replication in vitro in cells from subjects previously immunized with vaccinia virus. BMC Immunol 11:23PubMedCrossRefGoogle Scholar
  100. Weller SC, Davis-Beaty K (2002) Condom effectiveness in reducing heterosexual HIV transmission. Cochrane Database Syst Rev Issue 1 Art. No. CD003255Google Scholar
  101. Young H (2010) False assumptions. BMC Public Health 10:209. URL: (Retrieved Dec. 23, 2010)
  102. Zulu K, Bulawo ND, Zulu W (2006) Circumcision razor a preventative tool or a strategic vector in the transmission of HIV? A case of Zambia. Poster presented at XVI international AIDS conference, Toronto, Canada, 13–18 August 2006Google Scholar

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© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Faculty of Humanities and Social Sciences, Bond UniversityQueenslandAustralia

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