Summarising Male Circumcision Efficacy: Results of the three

randomised clinical trials

Neil A MartinsonPerinatal HIV Research Unit

Three Randomised Control Trials of Male Circumcision

• Orange Farm – South Africa Nov 2005

• Kisumu – Kenya Feb 2007

• Rakai – Uganda Feb 2007

Today: Feb 2010

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)

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).

Answers of a trial

Under “ideal” conditions• Is circumcision better than not circumcising?

• If better, by how much?

• Is it safe?

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

HIV negative men

Randomised

The three studies: design

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

Results 2: Rakai - Uganda

Time Circ group Uncirc group

0-6 months 1.2% 1.6%

6-12 0.4% 1.2%

12-24 0.3% 1.2%

ALL 0.7% 1.3%

Gray et al Lancet 2007

Overall efficacy of male circumcision in preventing HIV acquisition: 55%

8% had adverse event related to circ.

Results 3: Kisumu - Kenya

Time interval Circ group Uncirc group

0-6 months 0.8% 1%

6-12 0.2% 1.4%

12-18 0% 0.7%

18-24 1% 1.2%

ALL 2.1% 4.2%

Overall efficacy of male circumcision in preventing HIV acquisition: 53%

1.7% adverse events related to circ

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

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

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

Thank you for your attention

ALVAC®-HIV (vCP1521) • Recombinant canarypox vector vaccine genetically

engineered to express HIV-1 gp120 (subtype E: 92TH023) linked to the transmembrane anchoring portion of gp41 (subtype B: LAI), and HIV-1 gag and protease (subtype B: LAI).

AIDSVAX® B/E• Bivalent HIV gp120 envelope glycoprotein vaccine

containing a subtype E envelope from the HIV-1 strain CM244 and a subtype B envelope from the HIV-1 strain MN.

HIV VaccineAcquisition Endpoint: Modified Intent-to-Treat (mITT)

Vaccine infections: 51Placebo infections: 74p = 0.04Efficacy: 31.2%95% CI (OBF): 1.1, 51.2

Vaccine infections: 51Placebo infections: 74p = 0.04Efficacy: 31.2%95% CI (OBF): 1.1, 51.2

Prob

abilit

y of

HIV

-1 In

fect

ion

(%)

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

YEARS

0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5

.38

.15

.64

.41

.84

.58

.96

.68

PlaceboVaccine

Placebo

Vaccine