Randomized, Controlled Intervention Trial ofMale Circumcision for reduction of HIVInfection Risk: The ANRS 1265 Trial
PLoS Medicine Nov 2005;2(11):1112-22
CPCD Journal clubG vd Berk
History Male circumcision (MC)• Possibly oldest and most
common surgery, 20-25%of men circumcised
• Simple procedure thatconfers many benefits
• Risks
• Cultural context
Biological rational
• Foreskin– Inner mucosa is rich in HIV target cells– Associated with infections (GUD/balanitis/phimosis)– During intercourse foreskin is retracted over shaft
(microtears)
• After circumcision– Only vulnerable mucosa is meatus– External foreskin/shaft keratinized & less vulnerable
Level of evidence
• MC protects against:– Cancer of the cervix– Cancer of the penis– UTI`s , balanitis, phimosis in young children
• Protective effect MC against HIV infectiononly based on observational data
HIV and male circumcision—a systematic review with assessment of the quality of studies
Siegfried et al Lancet Infectious diseases 2005
Randomized controlled trials
• 3 RCT started: RSA Uganda Kenya
• Uganda / Kenya interim analyses 2006
• RSA trial– stopped after interim analysis results– Results published in 2005
Randomized, Controlled Intervention Trial ofMale Circumcision for reduction of HIVInfection Risk: The ANRS 1265 Trial
PLoS MedicineNov 2005;2(11):1112-22
Objectives study
• Primary Objective– Determine the impact of MC on the acquisition
of HIV by young men
• Secondary Objective– Assess behavioural factors known to be
associated with HIV serostatus in explainingthe possible impact
Methods (1)– Orange Farm– Recruitment Jul 02 – feb 04– Randomization via envelopes– At each visit:
• Face-to-face questionnaire about sexual behaviour• Blood sample• Genital examination• Individual counseling session
– Condom provision– VCT
Methods (2)
Background characteristics
Trial Profile
Multivariate RR of HIV incidence
Adverse events during sugery / <1 month after
Adverse events at the end of follow-up
Conclusions
• First RCT demonstrating a strongprotective effect of safe MC on HIVacquisition by males
• Consistent with expectation• Partial protection; short-term effect• Sub-saharan context• Reduction of female to male transmission• Public health intervention
Discussion
• How about male to female transmissionprevention ?
• Public health intervention;when/where/how ?
• Beware of false perceptions of security
Discussion
• How about male to female transmissionprevention ?
MC and male to female HIV&STItransmission in Rakai
• Female infection RR (CI)– HIV 0.74 (0.63-0.89)– BV 0.79 (0.69-0.91)– Trichomonas 0.65 (0.55-0.77)– HSV-2 0.82(0.62-1.07)– Chlamydia 1.06(0.61-1.84)– Gonorrhea 1.19(0.51-2.79)– Syphilis 1.08(0.99-1.32)– HPV 0.72(0.46-1.12)
Gray et al, CROI 2006
Discussion
• Public health intervention;when/where/how ?
• CAPE TOWN, South Africa -- A South African AIDSexpert Saturday advocated male circumcision as thebest available "vaccine" against the virus in his country,where an estimated 6 million people are infected andmore than 600 people die every day.
• Francois Venter told a congress of health activists in theTreatment Action Campaign that a recent survey in theSoweto township indicated that circumcised men were65 percent less likely to contract AIDS than those whohad not been circumcised.
• "We dream of a vaccine which has this efficacy," saidVenter, clinical director of the Reproductive Health andHIV Research at the University of Witwatersrand. "Theresults are phenomenal."
Trial location
Characteristics of follow-up period
