randomized, controlled intervention trial of male

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