summarising male circumcision efficacy: results of the three randomised clinical trials neil a...
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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
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
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