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Circumcision Cuts HSV-2 Risk in Ugandan Men and STDs in Their Wives
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15th Conference on Retroviruses and Opportunistic Infections
February 3-6, 2008
Boston
Mark Mascolini
Male circumcision prevents infection with herpes simplex virus type 2 (HSV-2) in men and lowers rates of sexually transmitted diseases (STDs) in their wives, according to further scrutiny of randomized trial results in Rakai, Uganda [1]. Separate analysis of another Rakai cohort found that circumcision may raise the risk of HIV transmission to wives, if men resume sex too soon after circumcision [2].
Rakai researchers evaluated 2787 men without HSV-2 infection, 1400 of them randomized to circumcision and 1387 randomized to delay circumcision for 2 years [1]. The Rakai team and two separate groups reported earlier that circumcision lowers the risk of HIV infection up to 60% in men. Other research indicates that HSV-2 doubles or triples the chance of HIV infection.
While 7.6% of circumcised men became infected with HSV-2 during 2 years of follow-up, 10.1% of the uncircumcised group picked up HSV-2. Statistical analysis determined that circumcision lowered HSV-2 risk 25% (relative risk [RR] 0.75, 95% confidence interval [CI] 0.59 to 0.96, P = 0.02). Men in all sociodemographic and behavioral subgroups shared this reduced risk.
Among 95 men in whom lab studies found what caused genital ulcers, HSV-2 proved the culprit in 86 (90.5%). And among 36 men who got infected with HIV during the trial, 58% had HSV-2 infection earlier or picked up HIV and HSV-2 during the study.
Rakai investigator Ronald Gray proposed that the main way circumcision protects men from HIV infection is by removing highly vulnerable foreskin. But the HSV-2 findings, he added, suggest that circumcision may also ward off HIV by a second means-protecting men from HSV-2 and the genital ulcers it causes.
More than 1600 HIV-uninfected wives of men in the trial had significantly lower risks of numerous sexually transmitted diseases after 1 year of follow-up if their husband was circumcised than if he was not:
- 22% lower risk of symptomatic genitourinary disease (RR 0.78, 95% CI 0.63 to 0.97)
- 48% lower risk of trichomoniasis (RR 0.52, 95% CI 0.05 to 0.98)
- 40% lower risk of bacterial vaginosis (RR 0.60, 95% CI 0.38 to.094)
- 61% lower risk of severe bacterial vaginosis (RR 0.39, 95% CI 0.24 to 0.64)
Women with normal vaginal flora when the trial began had a 20% lower risk of progression to bacterial vaginosis if their husband was circumcised (RR 0.80, 95% CI 0.65 to 097). And women who already had vaginosis when the trial began had an 18% lower risk that vaginosis would persist if their husband was circumcised (RR 0.82, 95% CI 0.72 to 0.96).
Earlier research indicates that STDs raise women's risk of HIV infection, but despite the just-noted findings, a separate analysis by the Rakai team found no evidence that an HIV-infected husband's circumcision protects his wife from HIV [2]. Indeed, this study uncovered a hint of a higher HIV risk in wives of circumcised men if an HIV-infected man had sex before his circumcision wound completely healed. The findings disappointed researchers because earlier observational results suggested male circumcision may protect female partners from HIV.
Rakai investigator Maria Wawer called it "imperative" that couples not resume sex too soon after a man gets circumcised. Generally, she suggested, husbands should wait 6 to 8 weeks after circumcision before resuming coital sex.
This analysis involved 93 couples with an HIV-infected, circumcised husband and 68 couples with an HIV-infected, uncircumcised husband. Wawer told journalists the study was necessary because enthusiasm for circumcision in Africa means many men already infected with HIV will get the operation so others do not suspect their infection.
Through 2 years of follow-up, HIV incidence in wives of circumcised men measured 13.8 cases per 100 person-years, versus 9.6 cases per 100 person-years in wives of uncircumcised men, but this difference lacked statistical significance (P = 0.42). HIV incidence was highest among women in the first 6 months of follow-up, 27.3 cases per 100 person-years in the circumcision group and 17.8 per 100 person-years in the control group (P = 0.41).
The HIV transmission rate ran higher among men who had sex more than 5 days before certified wound healing (28%) than among those who waited until within 5 days of certified healing (9.5%). Those results suggested that HIV-infected men with open circumcision wounds pose a higher risk of infecting their mates, perhaps because they may transmit the virus both in semen and in blood that seeps through the wound. Notably, the Rakai team found that circumcision wounds heal more slowly in men with HIV than in their uninfected counterparts.
Wives of circumcised men did not differ from those of uncircumcised men in condom use, bacterial vaginosis, vaginal discharge, painful urination, or genitourinary disease. Circumcision did lower the risk of genitourinary disease in circumcised men by about one third compared with uncircumcised men.
Wawer stressed the need for careful education and follow-up of couples before and after circumcision.
References
1. Tobian A, D Serwadda D, Quinn T, et al. Trial of male circumcision: prevention of HSV-2 in men and vaginal infections in female partners, Rakai, Uganda. 15th Conference on Retroviruses and Opportunistic Infections. February 3-6, 2008. Boston. Abstract 28LB.
2. Wawer M, Kigozi G, Serwadda D, et al. Trial of male circumcision in HIV+ men, Rakai, Uganda: effects in HIV+ men and in women partners. 15th Conference on Retroviruses and Opportunistic Infections. February 3-6, 2008. Boston. Abstract 33LB.
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