1. Summarising Male Circumcision Efficacy: Results of the three randomised clinical trials Neil A Martinson Perinatal HIV Research Unit

2. Three Randomised Control Trials of Male Circumcision Orange Farm – South Africa Nov 2005 Kisumu – Kenya Feb 2007 Rakai – Uganda Feb 2007 Today: Feb 2010

3. Efficacy How well an intervention works when studied in under rigorous conditions of a RCT. Percentage reduction in disease events by providing the intervention. Control group/arm– no circumcision Intervention group/arm- circumcision (but in all other respects groups are v. v. similar)

4. Conditions of a trial Well funded Excellent staff – trained and supervised Adverse events reported immediately Monitors – oversee every aspect of the trial Participants in trial ≠ general population Numerous: visits, samples, questions No visit – immediately triggers retrieval More attention than real life (safe sex).

5. Answers of a trial Under “ideal” conditions Is circumcision better than not circumcising? If better, by how much? Is it safe?

6. Trial jargon Male circumcision – removal of virtually all penile foreskin by a trained health worker using sterile surgical techniques. Randomisation: Subjects allocated to intervention or control group by chance (but in equal numbers). HIV acquisition: becoming infected with HIV Adverse event: unwanted side effect of intervention

7. Circ Follow up 6 moFollow up 12 mo Final HIV Assessment @ 24 mo No circ Follow up 6 moFollow up 12 moFollow up 18 mo Final HIV Assessment @ 24 mo Circ HIV negative men Randomised The three studies: design

8. Results 1: Orange Farm Auvert et al PLoS Medicine 2005 Overall efficacy of male circumcision in preventing HIV acquisition by young men: 60% 3.6% had an adverse event related to circ

9. Results 2: Rakai - Uganda TimeCirc groupUncirc group 0-6 months1.2%1.6% 6-120.4%1.2% 12-240.3%1.2% ALL0.7%1.3% Gray et al Lancet 2007 Overall efficacy of male circumcision in preventing HIV acquisition: 55% 8% had adverse event related to circ.

10. Results 3: Kisumu - Kenya Time intervalCirc groupUncirc group 0-6 months0.8%1% 6-120.2%1.4% 12-180%0.7% 18-241%1.2% ALL2.1%4.2% Overall efficacy of male circumcision in preventing HIV acquisition: 53% 1.7% adverse events related to circ

11. Combining all 3 “ The results indicate compelling evidence that male circumcision, when conducted using a medical procedure, reduces the acquisition of HIV by heterosexual men by between 38% and 66% over 24 months. Incidence of adverse events is very low, indicating that male circumcision, when conducted under these conditions, is a safe procedure. “ Siegfried N et al Cochrane Database 2009

12. Benefits restricted to men! A trial of circumcising HIV-infected men showed no reduction in HIV acquisition by female partners of circumcised men. Those who resumed sex early were at higher risk of acquiring HIV from their male partner. Wawer M et al Lancet 2009

13. What else is there to prevent HIV? Behaviour changes (ABC) – Condom use – Reduce concurrent partners – Delay sexual debut Vaginal Microbicides Barriers (condoms and diaphragms) Vaccines Pre exposure prophylaxis Treatment as prevention

14. Thank you for your attention

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