By Liz Highleyman

Adult male circumcision is emerging as a potentially important public health measure for reducing the risk of HIV transmission to men during heterosexual sex. A previous study in South Africa showed that elective circumcision reduced men's HIV infection rate by 61% (Auvert et al 2005).

As previously reported, the National Institutes of Health (NIH) halted 2 ongoing circumcision trials in Kenya and Uganda this past December, after an interim analysis showed that the intervention reduced the risk of HIV infection by about half.

Now, final data from these 2 studies, published in the February 24, 2007 issue of The Lancet, shows that the risk reduction associated with circumcision may be even greater than expected.

Further findings from the Uganda study will be presented on Wednesday, February 28, in 2 late-breaker presentations at the 14th annual Retrovirus conference in Los Angeles.

The 2 trials involved:

2784 HIV negative men aged 18-24 in Kisumu, Kenya;

4996 HIV negative men aged 15-49 in Rakai, Uganda.

In both trials, HIV negative heterosexual men who expressed an interest in circumcision were randomly assigned to undergo the procedure either immediately or after a waiting period. All participants received condoms and HIV prevention counseling.

Some of the men assigned to the circumcision group in both studies never actually completed the procedure, while others in the waiting group were so eager to obtain the procedure - which has received considerable attention as a possible way to reduce HIV risk - that they had it done elsewhere before the waiting period ended.

Kenya Results

In the Kenya study, after a median 24 months of follow-up, there were 47 new HIV infections among uncircumcised men, compared with 22 among circumcised men.

The 2-year HIV incidence rate was 2.1% in the circumcision group and 4.2% in the control group (P = 0.0065).

The relative risk of HIV infection in circumcised men was 0.47, representing a risk reduction of 53%.

In an as-treated analysis that excluded men who were initially misdiagnosed as HIV negative or who did not complete the study as assigned, the risk reduction was 60%.

Adverse events related to the intervention resolved quickly.

No increase in behavioral risk was observed after circumcision.

Uganda Results

In the Uganda study, also over 24 months, there were 43 new HIV infections among uncircumcised men (1.33 per 100 person-years), compared with 22 among circumcised men (0.66 per 100 person-years).

The estimated efficacy of circumcision was 51%).

In an as-treated analysis, the efficacy was 55%, and in a Kaplan-Meier time-to-HIV-detection as-treated analysis, it was 60%.

HIV incidence was lower in the circumcision group than in the control group for all socio-demographic, behavioral, and sexually transmitted disease symptom subgroups.

Moderate or severe adverse events resolved with treatment.

Risk behaviors were similar in the circumcision and control groups during follow-up.

Conclusion

"Male circumcision significantly reduces the risk of HIV acquisition in young men in Africa," the authors of the Kenya study concluded. "Where appropriate, voluntary, safe, and affordable circumcision services should be integrated with other HIV preventive interventions and provided as expeditiously as possible."

"Male circumcision reduced HIV incidence in men without behavioral disinhibition," wrote the Uganda research team. "Circumcision can be recommended for HIV prevention in men."

A combined analysis of the as-treated data from these studies and the previous South African suggests that the overall reduction in HIV incidence in circumcised men may be as high as 65%.

In an accompanying commentary, Marie-Louise Newell of the University of KwaZulu-Natal, South Africa, and Till Barnighausen of the Harvard School of Public Health wrote that the latest findings are "proof of a permanent intervention that can reduce the risk of HIV infection in men."

"Circumcision is the most potent intervention in HIV prevention that has been described," concurred Kevin DeCock, MD, director of the World Health Organization (WHO) HIV/AIDS Programme, though he cautioned that it should not be considered a replacement for other HIV prevention methods such as condoms.

WHO and UNAIDS are scheduled to meet soon to discuss the implications of these studies in light of the shortage of medical personnel and lack of healthcare infrastructure in developing countries -- some of which already have waiting lists for elective adult circumcision. Anthony Fauci, MD, of the NIH indicated that the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) would consider funding expanded circumcision programs in resource-limited settings.

02/27/07

References

R C Bailey, S Moses, C B Parker, and others. Male Circumcision for HIV prevention in young men in Kismu, Kenya: a randomised controlled trial. The Lancet 369(9562): 643-656. February 24, 2007.

R Gray, G Kigozi, D Serwadda, and others. Male circumcision for HIV prevention in men in Rakai, Uganda: a randomised trial. The Lancet 369(9562): 657-666. February 24, 2007.
M-L Newell and T Barnighausen. Male circumcision to cut HIV risk in the general population. The Lancet 369(9562): 617-619. February 24, 2007.

B Auvert and others. Randomized, Controlled Intervention Trial of Male Circumcision for Reduction of HIV Infection Risk: The ANRS 1265 Trial. PLoS Medicine 2(11): e298. October 25, 2005.

R Gray, G Kigozi, D Serwadda, and others. Randomised trial of male circumcision for HIV prevention in Rakai, Uganda. 14th Conference on Retroviruses and Opportunistic Infections. Los Angeles. February 25-28, 2007. Abstract 155aLB.

M Wawer, R Gray, G Kigozi, and others. The effects of male circumcision on genital ulcer disease and urethral symptoms, and on HIV acquisition: an RCT in Rakai, Uganda. 14th Conference on Retroviruses and Opportunistic Infections. Los Angeles. February 25-28, 2007. Abstract 155bLB.