Sub-Saharan African randomised clinical trials into male circumcision and HIV transmission: Methodological, ethical and legal concerns

Gregory J. Boyle, George Hill

Research output: Contribution to journalArticleResearchpeer-review

35 Citations (Scopus)

Abstract

In 2007, WHO/UNAIDS recommended male circumcision as an HIV-preventive measure based on three sub-Saharan African randomised clinical trials (RCTs) into female-to-male sexual transmission. A related RCT investigated male-to-female transmission. However, the trials were compromised by inadequate equipoise; selection bias; inadequate blinding; problematic randomisation; trials stopped early with exaggerated treatment effects; and not investigating non-sexual transmission. Several questions remain unanswered. Why were the trials carried out in countries where more intact men were HIV-positive than in those where more circumcised men were HIV-positive? Why were men sampled from specific ethnic subgroups? Why were so many participants lost to follow-up? Why did men in the male circumcision groups receive additional counselling on safe sex practices? While the absolute reduction in HIV transmission associated with male circumcision across the three female-to-male trials was only about 1.3%, relative reduction was reported as 60%, but, after correction for lead-time bias, averaged 49%. In the Kenyan trial, male circumcision appears to have been associated with four new incident infections. In the Ugandan male-to-female trial, there appears to have been a 61% relative increase in HIV infection among female partners of HIV-positive circumcised men. Since male circumcision diverts resources from known preventive measures and increases risk-taking behaviours, any long-term benefit in reducing HIV transmission remains uncertain.

Original languageEnglish
Pages (from-to)316-334
Number of pages19
JournalJournal of Law and Medicine
Volume19
Issue number2
Publication statusPublished - Dec 2011

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Male Circumcision
Randomized Controlled Trials
HIV
Safe Sex
Selection Bias
Lost to Follow-Up
Random Allocation
Risk-Taking
HIV Infections
Counseling
trend
WHO
counseling
incident
Infection

Cite this

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abstract = "In 2007, WHO/UNAIDS recommended male circumcision as an HIV-preventive measure based on three sub-Saharan African randomised clinical trials (RCTs) into female-to-male sexual transmission. A related RCT investigated male-to-female transmission. However, the trials were compromised by inadequate equipoise; selection bias; inadequate blinding; problematic randomisation; trials stopped early with exaggerated treatment effects; and not investigating non-sexual transmission. Several questions remain unanswered. Why were the trials carried out in countries where more intact men were HIV-positive than in those where more circumcised men were HIV-positive? Why were men sampled from specific ethnic subgroups? Why were so many participants lost to follow-up? Why did men in the male circumcision groups receive additional counselling on safe sex practices? While the absolute reduction in HIV transmission associated with male circumcision across the three female-to-male trials was only about 1.3{\%}, relative reduction was reported as 60{\%}, but, after correction for lead-time bias, averaged 49{\%}. In the Kenyan trial, male circumcision appears to have been associated with four new incident infections. In the Ugandan male-to-female trial, there appears to have been a 61{\%} relative increase in HIV infection among female partners of HIV-positive circumcised men. Since male circumcision diverts resources from known preventive measures and increases risk-taking behaviours, any long-term benefit in reducing HIV transmission remains uncertain.",
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Sub-Saharan African randomised clinical trials into male circumcision and HIV transmission : Methodological, ethical and legal concerns. / Boyle, Gregory J.; Hill, George.

In: Journal of Law and Medicine, Vol. 19, No. 2, 12.2011, p. 316-334.

Research output: Contribution to journalArticleResearchpeer-review

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