Circumcision May Protect Insertive Partners against HIV Transmission during Anal Sex, and May also Reduce Risk of Syphilis

SUMMARY: An Australian study published in the November 13, 2009 issue of AIDS showed that circumcision may reduce the risk that an insertive partner (or "top") will become infected with HIV during anal sex, adding to the mixed data about the protective effects of the procedure for men who have sex with men. Another study, appearing in the December 15, 2009 Journal of Infectious Diseases, indicated that circumcision helped protect HIV negative men from acquiring syphilis. A third study found that men with a larger foreskin area were more susceptible to HIV infection, helping explain the biological basis of circumcision's protective effect.

By Liz Highleyman

A series of large randomized trials in Africa have convincingly demonstrated that adult male circumcision can reduce the risk of HIV acquisition by as much as 60%. But these studies included young heterosexual men, and it is unclear whether men who have sex with men (MSM) might derive similar prevention benefits. In addition, epidemiological evidence has not revealed a lower rate of HIV infection among circumcised compared with uncircumcised men in high-income areas such as the U.S., Europe, and Australia.

David Templeton from the National Centre in HIV Epidemiology and Clinical Research at the University of New South Wales and colleagues assessed circumcision status as a risk factor for HIV seroconversion in gay men. At the 2007 International AIDS Society, the investigators reported that circumcision had no protective effect in this population.

The present analysis included 1426 initially HIV negative homosexual men enrolled in the prospective Health in Men (HIM) cohort in Sydney, Australia. About two-thirds of the men (n = 938) were circumcised. The men were recruited primarily through community-based sources between 2001 and 2004, and were followed through mid-2007. Participants underwent annual HIV testing and provided detailed information on their sexual activities and risk behaviors every 6 months.

The researchers evaluated HIV incidence in circumcised versus uncircumcised participants, stratified by whether or not the men predominantly practiced the insertive ("top") or receptive ("bottom") role in anal intercourse.

Results

	Among the cohort as a whole, 53 HIV seroconversions occurred during a median follow-up period of about 4 years, for an incidence rate of 0.78 per 100 person-years.
	In a multivariate analysis controlling for behavioral risk factors, circumcision was associated with a slight reduction in the risk of seroconversion, but this did not reach statistical significance (hazard ratio 0.78; P = 0.424).
	Among the one-third of study participants (n = 435) who reported a preference for insertive anal intercourse, 7 seroconversions occurred, with 5 of them among the 156 uncircumcised men.
	In this subgroup, circumcision was associated with a significant reduction in HIV incidence after controlling for age and unprotected sex (hazard ratio 0.11; P = 0.041).
	Men who reported such a preference "overwhelmingly" practiced only insertive unprotected anal intercourse, but a few also took the receptive role.
	Circumcision again did not significantly reduce the risk of HIV infection among men who reported exclusively engaging in (rather than preferring) insertive anal sex.

"Overall, circumcision did not significantly reduce the risk of HIV infection in the HIM cohort," the investigators concluded. "However, it was associated with a significant reduction in HIV incidence among those participants who reported a preference for the insertive role in anal intercourse.

The study is limited by its small numbers, which reduce its statistical power. For example, men who reported practicing exclusively unprotected insertive sex contributed only about 10% of total follow-up data.

The authors estimated that lack of circumcision contributed to 9% of HIV infections in the cohort as a whole -- or about 75% among men with a preference for insertive anal sex -- and suggested that, "Circumcision may have a role as an HIV prevention intervention in this subset of homosexual men."

In a related study published in the December 15, 2009 Journal of Infectious Diseases, the University of New South Wales team looked at the cost-effectiveness of 4 circumcision strategies for MSM in a "resource-rich" setting. The researchers created a mathematical model to estimate the costs, outcomes, and cost-effectiveness of different strategies, compared with the status quo.

The authors estimated that 2%-5% of HIV infections would be averted per year, with initial costs ranging from $3.6 million to $95.1 million, depending on the strategy. The number of circumcisions needed to prevent a single seroconversion would range from 118 to 338.

Circumcision of MSM who practiced insertive intercourse would save $21.7 million over 25 years, but would require a $62.2 million investment. Circumcising 100% of all MSM, or all MSM aged 35-44, would both be cost?effective, but the latter would require a smaller investment. The least cost?effective approach, they determined, was circumcision of young MSM near their "sexual debut."

In conclusion, the researchers wrote, "Circumcision of adult MSM may be cost-effective in this resource?rich setting. However, the intervention costs are high relative to the costs spent on other HIV prevention programs."

Circumcision and STDs

In another study described in the same journal, Templeton's team also analyzed the link between circumcision and other sexually transmitted diseases (STDs) among participants in the Sydney Health in Men cohort. Between enrollment in 2001-2004 and the end of follow-up in 2007, the men were offered annual STD testing.

Results

	Circumcision was not associated with numbers of prevalent (total) or incident (new) infections with herpes simplex virus 1 (the usual cause of oral herpes, or cold sores), herpes simplex virus 2 (the usual cause of genital herpes), or self-reported genital warts (cause by human papillomavirus, or HPV).
	There was also no independent association between circumcision and incident urethral gonorrhea or chlamydia.
	Circumcision was associated with a significantly reduced risk of new syphilis infections (hazard ratio 0.35), but not prevalent syphilis (odds ratio 0.71).
	The association between circumcision and syphilis was somewhat stronger among men who reported predominantly insertive unprotected anal intercourse (hazard ratio 0.10).

"Circumcised men were at reduced risk of incident syphilis but no other prevalent or incident [STDs]," the investigators concluded. "Circumcision is unlikely to have a substantial public health impact in reducing acquisition of most [STDs] in homosexual men."

Foreskin Area

Finally, looking back at the data from the aforementioned large African circumcision trials, G. Kigozi from the Rakai Health Sciences Program in Uganda retrospectively assessed whether foreskin surface area was associated with HIV acquisition prior to circumcision, which could illuminate how an intact foreskin facilitates infection. Results were published in the October 23, 2009 issue of AIDS.

The analysis included 965 initially HIV negative men enrolled in a community cohort who subsequently underwent circumcision. In 2 randomized trials of adult circumcision, the surface area of the foreskin was measured after surgery using standardized procedures.

The researchers estimated HIV incidence per 100 person-years prior to circumcision, and its association with foreskin surface area categorized into quartiles.

Results

A total of 48 new HIV infections occurred during the follow-up period.

The average foreskin surface area was significantly larger among men who became infected with HIV compared with uninfected men (43.3 vs 36.8 cm, respectively; P = 0.01).

HIV incidence rates were as follows:

	.80 per 100 person-years (or 8 per 994.9 person-years) for men with foreskin surface areas in the lowest quartile (<26.3 cm);
	0.92 per 100 person-years (or 9 per 975.3 person-years) for those with foreskin areas in the second quartile (26.4-35.0 cm);
	0.90 per 100 person-years (or 8 per 888.5 person-years) for men with foreskin area in the third quartile (35.2-45.5 cm);
	2.48 per 100 person-years (or 23 per 926.8 person-years) for men with foreskin surfaces areas in the highest quartile (> 45.6 cm).

Compared to men with foreskin surface areas in the lowest quartile, the adjusted incidence rate ratio of HIV acquisition for men in the highest quartile was 2.37, or more than double the risk.

Based on these findings, the study authors concluded, "The risk of male HIV acquisition is increased among men with larger foreskin surface areas."

The investigators suggested that a larger foreskin area may contain more cells, such as Langerhan's cells, that are susceptible to HIV infection. For this reason, they added, circumcision providers should be careful not to a leave a margin of vulnerable mucosal foreskin tissue when performing the procedure.

11/24/09

References

D Templeton, F Jin, L Mao, and others. Circumcision and Risk of HIV Infection in Australian Homosexual Men. AIDS 23(17): 2347-2351. November 13, 2009. (Abstract).

J Anderson, D Wilson, DJ Templeton, and others. Cost-Effectiveness of Adult Circumcision in a Resource-Rich Setting for HIV Prevention among Men Who Have Sex with Men. Journal of Infectious Diseases 200(12): 1803-1812. December 15, 2009.(Free full text).

D Templeton, F Jin, GP Prestage, and others. Circumcision and Risk of Sexually Transmissible Infections in a Community-Based Cohort of HIV-Negative Homosexual Men in Sydney, Australia. Journal of Infectious Diseases 200(12): 1813-1819. (Free full text).

G Kigozi, M Wawer, A Ssettuba, and others. Foreskin surface area and HIV acquisition in Rakai, Uganda (size matters). AIDS 23(16): 2209-2213. October 23, 2009. (Abstract).