Question

• In young sexually active males, does circumcision versus remaining uncircumcised reduce the risk of HIV infection?

Clinical Bottom Lines

1. The relative risk of HIV infection in circumcised men was 0.47, corresponding to a risk reduction of acquiring HIV of 53% and a NNT of 47.
2. Overall, the treatment (circumcision) was safe, with an adverse event rate of 1.5%, none of which were considered serious and all resolved quickly.
3. No significant change in sexual behavior was observed in circumcised men.

Summary of Key Evidence

1. 6686 African men aged 18-24 years in Kisumu, Kenya were initially recruited for the study, 98% were of the ethnic group Luo who traditionally don’t circumcise.¹
2. Key inclusion criteria included uncircumcised, HIV negative, sexually active and Hemoglobin of greater than 9. Participants were excluded if their foreskin covered less than half of the glans, any bleeding disorders or other contraindications to surgery, or they had an absolute indication for circumcision.
3. 2784 participants were randomized to immediate circumcision (n=1391) or control (delayed circumcision, n=1393). There were few major differences in baseline characteristics between the two groups.
4. Post circumcision follow up was done over a 30 day period to assess for adverse events, and they were instructed to abstain from sexual activity during this time.
5. Follow up for HIV status was incomplete in 240 (8.6%) of participants, and 86% completed the full 24 months of follow-up. Intention to treat analysis showed a 2-year HIV incidence of 2.1% (95% CI 1.2-3) in the circumcised group and 4.2% (95% CI 3-5.4) in the control group. The study was ended early because interim analysis showed clear benefit of circumcision.
6. Limitations to the study included lack of blinding, self reporting of sexual behaviors, 8.6% of participants had incomplete HIV test results, only 86% made all scheduled follow up visits, trial was ended early, treatment (circumcision) can’t be standardized, and poor generalisability of the population to the rest of Africa and to other nations.

Additional Comments

• Studies have shown a biological basis for the protective effect observed, as the inner foreskin has been shown to be poorly keratinized, contain a high proportion of HIV target cells such as Langerhans’ cells, and in vitro have a higher uptake rate of HIV than female cervical cells.^4,5
• 2 other RCTs exist, showing similar evidence with 51% reduction in a Ugandan population3 and 60% in a South African population.²
• Simulation models based on assumption of 60% protective effect of circumcision estimate 2 million new HIV infections and 300,000 deaths can be prevented in Sub-Saharan Africa over the next 10 years if 100% of their population was circumcised.¹ Models also predict it would be cost effective.¹
• Concerns remain that belief that circumcision protects fully against HIV could lead to changes in sexual behaviors, as well as increased risk of infection in the 30 day post circumcision period.
• It is unclear what impact this would have in developed nations such as the US, where most circumcisions are done in the neonatal period, the HIV prevalence is much less, and most infections are attained via homosexual transmission or IV drug use as opposed to heterosexual transmission. The AAP is currently reevaluating their previous circumcision policy which states there is no medical necessity.

Citation

1. Bailey RC, et al. Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomised controlled trial. Lancet 2007;369:643-56.
2. Auvert B, et al. Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: the ANRS 1265 Trial, PLoS Med 2005: e298.
3. Gray RH, et al. Male circumcision for HIV prevention in men in Rakai, Uganda: a randomised trial. Lancet 2007;369:657-66.
4. McCoombe SG, et al. Potential HIV-1 target cells in the human penis.AIDS 2006;20:1491-5.
5. Patterson BK, et al. Susceptibility to human immunodeficiency virus-1 infection of human foreskin and cervical tissue grown in explant culture. Am J Pathol 2002;161:867-73.
6. Seigfried N, et al. Male circumcision for prevention of heterosexual acquisition of HIV in men [Reviews]. The Cochrane Library

CAT Author: Megan Shaughnessey, MD

CAT Appraisers: John Frohna , MD

Date appraised: May 16, 2007