IAS: Circumcision prevents three out of four female-to-male HIV infections

The first ever randomized controlled trial (RCT) of male circumcision as an HIV prevention measure has produced such strong evidence of a protective effect that the trial has been halted early and all participants have been offered circumcision, the Third International IAS Conference on HIV Pathogenesis and Treatment in Rio de Janeiro heard on July 26^th.

There were only 35% as many infections in the circumcision arm as opposed to the control arm, implying that circumcision can prevent at least six out of ten female-to-male HIV transmissions.

However, when the results were analysed according to true circumcision status rather than by intervention group, the protective effect went up to 75%. This is because there were ‘crossovers’ between the intervention and control arms in that some men randomized to be circumcised were not, and some in the control arm were.

The trial, the first of four RCTs of circumcision being conducted in Africa, randomised 3,273 men aged 16 to 24 to be circumcised at the start of the trial or to be offered circumcision at the end of it 21 months later.

The men lived in the Orange Farm township near Johannesburg, South Africa. A previous acceptability study had found that 70% of the local male population said they were willing to be circumcised if it could prevent HIV, and in fact 20% already are, with a surprisingly late median age of circumcision of 17.

The HIV prevalence in the area is high, at 31.6% of the adult population. In the trial population 90% of men were sexually active by the start of the study, with a mean age of sexual debut of 16.6.

Circumcisions in the intervention arm were carried out by a surgeon under local anaesthesia and with post-operative pain relief given.

Presenter Bertran Auvert of the French HIV Research Institute INSERM stressed the safety of the procedure and said that there had been no deaths or permanent adverse effects in any participant. Thirty-one per cent complained of pain and 15% initially had problems with the changed appearance of their penis.

HIV incidence was measured at three and twelve months into the trial and finally at 21 months though the average follow-up period was in fact 20 months due to the premature termination of the trial.

Although all participants received intensive safer sex counselling and condoms, there were 51 HIV seroconversions in the control arm versus 18 in the circumcision arm. This translates as HIV incidences of 2.2% and 0.77% a year respectively.

In the control arm there were nine, 15 and 27 new infections at three, 12 and 21 months and in the circumcision arm two, seven and nine.

"This is the first RCT demonstrating a strong protective effect of safe male circumcision", said Auvert.

He added that as a short term study it could not predict the long term effect of circumcision, but that its compelling results now demanded discussions on the use of circumcision as a public health measure.

Circumcision may also substantially cut the male to female transmission rate, the conference heard. Ronald Gray, one of the investigators behind the long-standing Rakai prevention cohort in Uganda, said that studies at Rakai and other centres had indicated that HIV-negative women with circumcised HIV-positive partners had only 0.41 as many seroconversions as partners of uncircumcised men.