There was a trend towards higher HIV incidence in the wives of HIV positive men who were circumcised compared with wives of men left uncircumcised, in the latest prevention study conducted in Rakai province, Uganda, investigators revealed at a press conference on the opening day of the Fifteenth Conference on Retroviruses and Opportunistic Infections in Boston.
In 2006, a randomised trial of circumcision in Rakai reported that circumcision led to an almost 50% reduction in a man’s risk of acquiring HIV through heterosexual sex. The impact of male circumcision on transmission of HIV to the female partner remains unknown, and the study reported today set out to examine the effects.
In the Gates Foundation-funded study, 1015 HIV positive men were randomised either to immediate circumcision or circumcision delayed by two years. Of these 770 were married and were asked to invite their wives into the study; 566 wives enrolled of whom 245 (43%) were HIV-negative and therefore in a serodiscordant relationship.
The annual HIV incidence rate in the wives of the men who were circumcised was 14.4% over two years of follow-up compared with 9.1% in women whose partners remained uncircumcised. This result may be due to chance as it was not statistically significant, but was described as “unexpected and somewhat disappointing” by lead investigator Maria Wawer of Johns Hopkins University, Baltimore. It was not due to behavioural disinhibition; condom use was the same in both arms.
Wawer said that these results were an additional challenge to the rolling-out of mass circumcision programmes in Africa, which are expected following the positive results from three randomised controlled trials of circumcision in HIV negative men, one of them conducted within the Rakai community.
She said: “It is inevitable that some HIV positive men will seek circumcision. It is the only HIV prevention modality that leaves a mark, and no one wants to be the only guy in the village who is uncircumcised if it becomes regarded as a mark of HIV.”
If the increased incidence in the partners of circumcised HIV-positive men is real and not due to chance, it may largely have been due to men resuming sex before their circumcision wound was certified as having healed, Wawer added. Five out of 18 wives of men who resumed sex more than five days prior to certified wound healing (28.8%) became HIV-positive themselves. In contrast six out of 63 wives of men who resumed sex no earlier than five days prior to certified wound healing were infected (9.5%) and this was statistically equivalent to six out of 68 wives of men who remained uncircumcised (8.8%).
After six months, HIV incidence declined to 5.7% a year in partners of circumcised men and 4.1% in wives of uncircumcised men, which was also not statistically significant.
The results may be partly due to HIV-positive men tending to heal more slowly from circumcision than HIV negative men. Seventy-one per cent of HIV positive men had healed completely by 30 days after circumcision, compared with 83.2% of HIV negative men.
Wawer said: “It is imperative people don’t resume sex in the post-operative period, and because of this slightly longer healing time we are saying don’t resume sex until six to eight weeks after the operation.”
She added that even in the RCT in HIV negative men, the benefit from circumcision did not start to appear until more than six months after the operation.
Effect of circumcision on STIs
There was better news from this and another study of the effect of circumcision on sexually transmitted infections (STIs). In the Rakai study, the circumcised HIV-positive men had a third less genital ulcer disease (GUD) than those who remained uncircumcised (10.1% versus 15.8%) and this was statistically significant (p = 0.002). However rates of all STIs and of bacterial vaginosis were the same in wives of circumcised and uncircumcised men.
Another study presented by Aaron Tobian of the same team investigated the effect of circumcision on the acquisition of genital herpes (HSV-2) in HIV-negative men, and on the incidence of GUD, bacterial vaginosis and trichomonas in their wives.
There was a 25% reduction in HSV-2 acquisition in the circumcised men, and a 25% reduction in GUD, a 20% reduction in bacterial vaginosis, and a 50% reduction in trichomonas in their wives. Severe bacterial vaginosis fell by 60% (two per cent in wives of circumcised men versus 6.5% in wives of uncircumcised). All these results were statistically significant.
Among 62 men who became HIV-positive during the trial, 38 (61%) either had HSV-2 before the trial (47%) or seroconverted simultaneously to HIV and HSV-2 (14%).
“All the STIs observed are cofactors of HIV,” Tobian commented. “These effects may influence the positive effect of circumcision on HIV acquisition.”
Wawer M et al. Trial of circumcision in HIV+ men in Rakai, Uganda: effects in HIV+ men and women partners. Fifteenth Conference on Retroviruses and Opportunistic Infections, Boston. Abstract 33LB. 2008.
Tobian A et al. Trial of male circumcision: prevention of HSV-2 in men and vaginal infections in female partners, Rakai, Uganda. Fifteenth Conference on Retroviruses and Opportunistic Infections, Boston. Abstract 28LB. 2008.